EuroPharma 2017 Press Kit

Related exhibitorEuroPharma

2017 EXPO WEST MEDIA KIT

EUROPHARMA, INC HEADLINES FOR EXPO WEST 2017

Anaheim, CA—Booth #1575

EuroPharma Now Employee-Owned

To celebrate 10th Anniversary, Terry Lemerond shares ownership of EuroPharma

Dr. Alexander Panossian Joins EuroPharma

Noted international herb expert appointed research and science director

Terry Naturally CuraMed and Curamin Lines continue to expand

Success of popular products leads to more formula offerings

Terry Naturally Expands BosMed Boswellia Line of Products

Clinically studied, uniquely standardized boswellia in new formulas

Awards—EuroPharma Continues Winning Streak

Ageless Radiance: Delicious Living Best Beauty Supplement
CuraMed Prostate: Taste for Life Supplement Essentials Award for Prostate Support
Curamin: Better Nutrition Best of Supplements Award for Pain Relief
Curamin Headache: Vitamin Retailer Best New Product of 2016
Propolis Extract: Taste for Life 2016 Immunity Essentials Award
Sucontral D: New Hope Network NEXTY for Best New Supplement

New Products

Ageless Radiance Skin Nutrition Launched By Terry Naturally

New oral formula shown to improve skin firmness by 55% and radiance by 62%

Cardio-VX1 Launched By Terry Naturally

Proprietary formulation combines nutrients and polyphenols to support heart strength

Terry Naturally Launches Cold Weather Wellness

Healthy immune system formula features clinically studied ingredients

Curamin Enhanced Whey Protein Launched By Terry Naturally

Multipurpose protein and pain relief for every body

Terry Naturally Launches Curamin Headache + Caffeine and Curamin Extra Strength + Caffeine

Curamin family expanded with new enhanced formulas

Terry Naturally Launches Fibroxia for Both Pain and Fatigue

Clinically studied nutrients combined with essential oils for broader activity

Terry Naturally Launches O’live

Active olive compounds for heart, brain, skin and more—without the calories

Terry Naturally Launches Rhulief Pain Relieving Balm

Over the counter topical medication approved for arthritis pain and more

Terry Naturally Launches Unique Weight Loss Product Slim-VX1

Clinically studied ingredient shown to support 7 times more weight loss

Studies

Curcumin–32 published clinical studies
Comfrey Cream–22 published clinical studies
Hintonia Latiflora–13 published clinical studies
Boswellia–3 published clinical studies

Terry Lemerond	Cheryl Myers, RN	Jacob Teitelbaum, MD
Ajay Goel, PhD	Holly Lucille, ND, RN	Gaetano Morello, ND
Alexander George Panossian, PhD & Doctor of Science

Bios of Scientific Advisory Board Members and Expert Sources

EuroPharma/Terry Naturally Success Story...

2017

EuroPharma, Inc.becomes an Employee Stock Ownership Plan (ESOP) company.

2016

A second Terry Naturallystore opens in Green Bay, WI, and EuroPharma expands corporate office.
Dr. Alexander George Panossian joins EuroPharma as the Director of Research and Science. He will also serve on the Scientific Advisory Board.

2015

Supplement pioneer Terry Lemerond receives first American Botanical Council (ABC) Champion Award.
Curaminreceives 22nd Award. Award was given by Delicious Living in the Pain Category.†

2014

EuroPharma launches Bacteril™for immune system support.*
WholeFoods Magazine announced Curamin as winner of annual Natural Choice Award.
Curamin named Taste for Life’s Essential Choice for Pain Relief.†

2013

Vitamin Retailer Magazine awards Curamin Best New Natural Remedy and Best New Specialty Herbal Awards.
Curamin Extra Strength awarded Delicious Living Magazine’s Best New Specialty Combination Formula and Pain Category Awards.†
Clinically studied SagaPro Bladder Health now available in the U.S.

2012

Curamin wins Best of Supplements, 5th consecutive year from Better Nutrition Magazine in pain category.†
Healthy Feet & Nerves™ wins Best New Products Award from Vitamin Retailer Magazine.
Healthy Knees & Joints™ named Best Joint Health Product by Delicious Living Magazine in Supplement Awards.
Curamin wins Essential Supplement Award from Taste for Life Magazine in pain category.†

2011

Dr. Ajay Goel, Ph.D., and Dr. Holly Lucille, N.D., R.N., join Scientific Advisory Board.
Curamin awarded 3 Vitamin Retailer Vity Awards in 3 separate categories.
Curamin wins Wholefoods Natural Choice Award.
Better Nutrition’s Best of Supplements Award goes to Curamin in pain category.†

2010

EuroPharma welcomes Jacob Teitelbaum, MD to the Scientific Advisory Board.
Curamin wins Better Nutrition’s Best of Supplements Award in pain category for the 3rd consecutive year.†
SinuCare™ wins Vitamin Retailer’s Vity Award for Best New Specialty Herbal Supplement.
AnxioFit-1, a unique, standardized, clinically tested echinacea extract, is launched.

2009

Launch of Vectomega, the first whole food, 100% salmon, phospholipid based EPA/DHA omega-3 fatty acid supplement.
Curamin is Vitamin Retailer’s Vity Award winner for Best New Natural Remedy.
Cuaramin wins Better Nutrition’s Best of Supplements Award in pain category for the 2nd year in a row.†

2008

Terry Lemerond is the recipient of the 2008 Natural Products Association Industry Champion Award.
Curamin wins Better Nutrition’s Best of Supplements Award in pain category.†

2007

Got Pain? EuroPharma launches Curamin.

2006

Terry Lemerond opens Terry Naturally, a retail store offering the finest quality nutritional products, body care, and natural, organic foods.

1998

After 15 years of scientific study by researcher A.K.M. Shamsuddin M.D., Terry Lemerond introduced the breakthrough combination of IP-6 and inositol, an unprecedented immune boosting supplement.

1993

Introduced Glucosamine Sulfate, providing Americans with the first clinically supported nutritional supplement for healthy joint support and creating the beginning of a $900 million dollar industry.

1986

Introduced deglycyrrhizinated licorice, an extract widely used in Europe to support the mucosa of the stomach, to the U.S.
Was the first U.S. manufacturer to produce peppermint oil in enteric-coated capsules, which allows the oil to reach the small intestine and eventually the colon, where it would be released for best results.

1982

Terry Lemerond introduced botanical standardization to the U.S. supplement industry. A standardized product contains a consistent amount of one or more active ingredients, helping ensure consumers “get what they pay for”.
Introduced standardized Ginkgo biloba to the U.S. market.

Introduced milk thistle, a natural liver support supplement, to the U.S. This comes after extensive scientific review of the merits of silymarin, an extract derived from the plant.

CONTACT: Dean Draznin Communications Dean Draznin dean@drazninpr.com

Office: 641-472-2257 Mobile: 323-397-2647

Diane Chojnowski diane@drazninpr.com Office: 641-209-9591 Mobile: 641-919-0385

EuroPharma 10th Anniversary Landmark: Now Employee-Owned!

GREEN BAY, WI, March 9, 2017—To celebrate EuroPharma’s tenth anniversary, founder and president Terry Lemerond has signed the papers to share ownership of his company with his employees. It’s a gift he hopes will reward their hard work and dedication and ensure the company continues to grow and progress in perpetuity.

EuroPharma’s Employee Stock Ownership Plan (ESOP) provides for the continued growth and continuity of the company he founded in 2007. Lemerond will remain President of EuroPharma and plans to lead the employee-owners for many years to come.

“EuroPharma is a wonderful company built by a strong team,” said Terry Lemerond. “When planning for the future, I did not want the company to be sold to an outsider. I feel that the people who helped me build this company and share the pride of our achievement deserve to have ownership. It feels fantastic to share the success with them.”

An ESOP traditionally helps employees maximize retirement income and offers security for the future. Giving employees ownership also can be a smart business-growth strategy. A recent study by researchers at the University of Iowa, Villanova University, and Indiana University, published in the Human Resource Management Journal found that employee ownership could make a company an average of 4% more profitable than others. Over 10 years, that represents huge potential growth.

“The ESOP gives me a way to achieve my ultimate dream,” said Lemerond, “which is to pass the success on to the next generation. My greatest joy is to see our employees flourish personally as their efforts meet with continued success. Employee ownership is a way to perpetuate the pride we all feel today and maintain our role as industry innovators for many years to come.”

EuroPharma, Inc., makers of the Terry Naturally brand, offers clinically proven and effective nutritional supplements that improve the health of America. Terry Lemerond, founder and president of EuroPharma, is well-known for innovation, and is credited as the first to introduce glucosamine sulfate and standardized Ginkgo biloba to the U.S. natural products market. Some of our current exclusive products include Curamin, winner of 28 awards for pain relief; CuraMed, containing the most clinically studied enhanced absorption curcumin in the world, with beneficial turmeric oil with turmerones, and the #1 product in its category according to SPINS data; SagaProfor bladder health; Vectomegafull-spectrum omega-3 salmon extract; TraumaplantComfrey Cream; and FastBlockAllergy Relief. The full line of products is available throughout the U.S. in both the health food store and independent pharmacies. At EuroPharma, Our Passion is Your Health™. For more information, visit www.EuroPharmaUSA.com.

CONTACT: Dean Draznin Communications Dean Draznin dean@drazninpr.com

Office: 641-472-2257 Mobile: 323-397-2647

Diane Chojnowski diane@drazninpr.com Office: 641-209-9591 Mobile: 641-919-0385

Dr. Alexander Panossian, Noted International Herbal Expert, Joins EuroPharma

Appointed research and science director for development of botanical formulations

GREEN BAY, WI, March 9, 2017—EuroPharma, Inc., makers of the Terry Naturallyand EuroMedicalines of dietary supplements and natural products, is pleased to announce that Alexander George Panossian, Ph.D., Dr. Sci., has joined their company as a consultant, and research and science director for product development as an expert in herbal products.

Dr. Panossian completed his doctorate in organic chemistry at the Yerevan State University and obtained his scientific degrees from Moscow’s Institute of Bioorganic Chemistry and Institute of Fine Chemical Technology. In Armenia, he worked for the National Academy of Sciences and the National Institute of Health. After the collapse of United Soviet Socialist Republics (USSR), Dr. Panossian was made a full professor of chemistry of natural and physiological active compounds in the Russian Federation. In 2003, he moved to Sweden where he worked for the Swedish Herbal Institute as head of research and development. During his scientific career, he was a guest scientist in the laboratory of Nobel laureate Bengt Samuelsson at the Karolinska Institute in Stockholm, at Munich University, and at King’s College in London. He has written or co-authored more than 170 articles in peer-reviewed journals.

Alexander Panossian is an advisory board member of the American Botanical Council (ABC) and also the Editor-in-Chief of Phytomedicine, International Journal of Phytopharmacology, and Phytotherapy (Elsevier, Germany).

“I am excited about our new R&D projects with Terry Lemerond, the man who introduced botanical standardization to the U.S. supplement industry in 1982,” says Dr. Panossian, “and he remains a leader in the verification of clinical efficacy and safety of nutritional supplements. This approach is in line with pharmaceutical standards for herbal medicinal products. I hope that the results of our innovative studies based on state-of-art research will directly benefit consumers.”

“Dr. Panossian will be available to help us reach the next level of growth, offering high quality, scientifically studied botanicals that make a real difference in the life and health of consumers,” says Terry Lemerond, president and founder of EuroPharma. “He has an incredible wealth of botanical knowledge. I am very happy he is joining our Scientific Advisory Board, as well as overseeing the next generation of botanical product development. It is an honor to work with such a world-renowned herbal expert.”

enhanced absorption curcumin in the world, with beneficial turmeric oil with turmerones, and the #1 product in its category according to SPINS data; SagaProfor bladder health; Vectomegafull-spectrum omega-3 salmon extract; TraumaplantComfrey Cream; and FastBlockAllergy Relief. The full line of products is available throughout the U.S. in both the health food store and independent pharmacies. At EuroPharma, Our Passion is Your Health™. For more information, visit www.EuroPharmaUSA.com.

CONTACT: Dean Draznin Communications Dean Draznin dean@drazninpr.com

Office: 641-472-2257 Mobile: 323-397-2647

Diane Chojnowski diane@drazninpr.com Office: 641-209-9591 Mobile: 641-919-0385

Terry Naturally’s CuraMed and Curamin Lines Continue to Expand

Success of popular products leads to more formula offerings

GREEN BAY, WI, March 9, 2017— EuroPharma, Inc., makers of the Terry Naturallybrand of dietary supplements, has expanded both its CuraMedand Curaminfamily of products, most over the past year, to include targeted formulas for specific areas of health support. The common denominator of all the formulas is the most clinically studied enhanced absorption curcumin in the world.

“I believe that the unique curcumin we use in both our CuraMed and Curamin lines has some of the most amazing health benefits I have ever witnessed in all my years in the natural health industry. These are products that can change lives. My passion is to reach even more people who are in need of these products, and by offering greater diversity in these formulations, I hope to expand their reach even farther,” states Terry Lemerond, president and founder of EuroPharma, Inc., makers of the Terry Naturally brand.

CuraMed 750 is the clinically studied dosage of patented curcumin blended with turmeric essential oil containing turmerones, for better absorption and enhanced bioactivity. CuraMed is the number one curcumin product in its category, according to SPINS*data. CuraMed is up to 500 times stronger at delivering curcumin than plain turmeric.^ This line’s newest additions are:

CuraMed Brain—designed to preserve mental agility, focus and clarity, with ingredients supporting healthy brain and acetylcholinesterase activity.
CuraMed Breast—formulated with strong, targeted synergistic vitamins and botanicals to support healthy breast cells.
CuraMed Prostate—provides cellular antioxidant protection, free radical defense, and healthy male hormonal balance to support healthy prostate-specific antigen (PSA) levels already within normal range.
CuraMed + DIM—contains French grape seed VX1, along with BioResponse DIMComplex for better absorption and improved estrogen balance and hormonal detoxification. BioResponse is the most clinically studied form of diindolylmethane (DIM).
CuraMed Effervescent—easily dissolvable effervescent tablets to provide an easy CuraMed curcumin delivery system for people who have difficulty swallowing tablets and capsules, or who prefer a liquid.

Curamin and Curamin Extra Strength are multiple award-winning, best-selling pain**products based on the combination of patented curcumin with turmeric essential oil and uniquely standardized boswellia as the foundation. The amino acid DLPA and the enzyme nattokinase play a supportive role in the product’s pain relieving activity. The line’s newest additions are:

Curamin PM—added nutrients like bioactive vitamin B6 (P-5-P) and melatonin for help with sleep and pain relief.
Curamin Athletic Pain—both pancreatic and plant sourced enzymes are added to the basic formula for reduction of post exercise pain and quicker muscle recovery.
Curamin Headache—strong ingredients like TRAACSmagnesium bisglycinate and P-5-P for proper neurological function and relief of occasional headaches.***
Curamin Low Back Pain—blended with targeted botanicals to stop occasional back pain for comfort and mobility.****

Terry Naturally’s line of CuraMed and Curamin products are available nationwide at quality health food retailers and integrative pharmacies.

*SPINScan Other Herbal Formulas, Total US - Natural Channel, 52 wk Data Ending 12/25/2016

**Occasional muscle pain due to exercise or overuse

***Occasional headaches due to stress or fatigue

****Occasional back muscle pain due to exercise or overuse

^ Based on enhanced absorption of CuraMed curcumin versus equivalent weight capsule of unstandardized turmeric containing 2% curcumin

CONTACT: Dean Draznin Communications Dean Draznin dean@drazninpr.com

Office: 641-472-2257 Mobile: 323-397-2647

Diane Chojnowski diane@drazninpr.com Office: 641-209-9591 Mobile: 641-919-0385

Terry Naturally Expands BosMed Boswellia Line of Products

Clinically studied, uniquely standardized boswellia in new formulas

GREEN BAY, WI, March 9, 2017— EuroPharma, Inc., makers of the Terry Naturallybrand of dietary supplements, has announced the expansion of the BosMed™family of products to include targeted formulas for specific areas of health support. All BosMed products feature an advanced, clinically studied form of boswellia that is uniquely standardized to provide up to 10 times more AKBA (acetyl-11- keto-B-boswellic acid) than unstandardized boswellia extracts. It is also purified to reduce levels (<5%) of beta boswellic acid, a pro-inflammatory compound that makes up approximately 20% of the boswellic acid family in unstandardized boswellia.

According to The Journal of the American Botanical Council: HerbalGram’s press release in 2016: “Boswellia, despite ranking 39th in this channel, had perhaps the best year of any supplement sold in mainstream retail outlets, with a 674% increase in sales over the previous year.”

“Boswellia is one of the most powerful botanical resources in our natural health tool chest today, and more consumers are learning about its incredible health benefits,” states Terry Lemerond, president and founder of EuroPharma, “We have created formulas with synergistic nutrients to better target how to help consumers with specific health needs.”

Products include:

BosMed 500 original formula: containing 500 mg clinically studied, uniquely standardized boswellia per softgel. Designed for healthy inflammation response.
BosMed Intestinal Bowel Support: a new product featuring BosMed boswellia, plus coriander, fennel, caraway,and peppermint oil CO2 extracts.Provides soothing relief from occasional bloating, gas, cramping, diarrhea, and other discomforts, while supporting daily digestive predictability.
BosMed Respiratory Support: a new product featuring BosMed boswellia plus ravintsara, thyme,and myrtle oil CO2 extractsfor healthy bronchial, lung, and sinus function, and healthy immune response.
BosMed + Frankincense Oil: a new product that contains clinically studied BosMed boswellia from Boswellia serrata, plus the CO2 extractof frankincense oil from Boswellia carteri. These two forms of boswellia combine to protect cells from the risk of oxidative damage and promote healthy cellular development.

Terry Naturally’s line of BosMed products are available nationwide at quality health food retailers and integrative pharmacies.

HerbalGram—Journal of the American Botanical Council press release. 2016. Issue: 111 Page: 67-73 Available at: http://cms.herbalgram.org/herbalgram/issue111/hg111-mktrpt.html

CONTACT: Dean Draznin Communications

Dean Draznin dean@drazninpr.com

Office: 641-472-2257 Mobile: 323-397-2647

Diane Chojnowski diane@drazninpr.com Office: 641-209-9591 Mobile: 641-919-0385

EuroPharma Continues Winning Streak

Terry Naturally wins multiple awards for top quality supplements

GREEN BAY, WI, March 9, 2017— EuroPharma, Inc.is pleased to announce that their Terry Naturallybrand of supplements has been honored with several natural products awards for excellence. Each year, top publications in the natural products industry recognize the industry’s best products based on feedback from industry leaders, retailers, and consumers. The Terry Naturally products are known for top quality and have received these awards in recent months:

CuraMed Prostate: Taste For Life Supplement Essentials Award
Curamin: Better Nutrition 2016 Best of Supplements Award – Best Pain Relief
Curamin Headache: Vitamin Retailer – Best New Products of 2016
SucontralD: New Hope Natural Media 2016 Best of Supplements Awards – Best New Supplement
Propolis Extract: Taste For Life 2016 Immunity Essentials Award
Acne Essentials™: Taste For Life 2016 Back To School Essentials Award
Ageless Radiance™: Delicious Living 2017 Beauty and Body Awards – Best Beauty Supplement

“We are thrilled to receive these awards from outstanding publications and industry leaders,” said Terry Lemerond, president and founder of EuroPharma. “We would like to thank Better Nutrition, Vitamin Retailer, New Hope Natural Media, Taste for Life, and Delicious Living for recognizing the top natural products in the health food industry. They do an outstanding job of educating retailers and the general public about the value of high-quality supplements and ingredients. We deeply appreciate their commitment to excellence.”

In ten years, Terry Naturally products have received 62 awards, including 30 awards for their bestselling Curamin line of effective pain-relieving products. Known for innovation, the Terry Naturally brand has been awarded “Best New Product” twelve times for their high quality products including:

Curamin
SinuCare™
SagaPro
Curamin Extra Strength
Sucontral D
Curamin Headache

Terry Naturally products are available nationwide at quality health food retailers and integrative pharmacies.

EuroPharma, Inc., makers of the Terry Naturally brand, offers clinically proven and effective nutritional supplements that improve the health of America. Terry Lemerond, founder and president of EuroPharma, is well-known for innovation, and is credited as the first to introduce glucosamine sulfate and standardized Ginkgo biloba to the U.S. natural products market. Some of our current exclusive products include Curamin, winner of 28 awards for pain relief; CuraMed, containing the most clinically studied enhanced absorption curcumin in the world, with beneficial turmeric oil with turmerones, and the #1 product in its category according to SPINS data; SagaPro for bladder health; Vectomegafull-spectrum omega-3 salmon extract; TraumaplantComfrey Cream; and FastBlockAllergy Relief. The full line of products is available throughout the U.S. in both the health food store and independent pharmacies. At EuroPharma, Our Passion is Your Health™. For more information, visit www.EuroPharmaUSA.com.

AWARD-WINNING FORMULA

Our Passion is Your Health'

Curamin.com

2016

betternutrition

BEST OF SUPPLEMENTS AWARD WINNER

Best of Supplements Award Winner, 2016,2015,2014,2012,201 1,2010,2009,& 2008

Better Nutrition Magazine

Pain Category^†

NAt URA L CHOICE AWAR DS

2016

ESSENTIALS

AWARD WINNER

- Vity Awards Winner, 2016, 2015, 2014, 2013, 2011, & 2009

Vitamin Retailer Magazine, in 5 categories:

• Best Herbal Supplement (2016, 2015, 2014 & 2011)

Best New Natural Remedy ( 2013, 2011 & 2009)
Best New Specialty Herbal (2013)
Best New Specialty Combination Formula (2013)
Best New Herbal Supplement (2011)

Natural Choice Award Winner, 2016, 2014, 2013, & 2011

WholeFoods Magazine

Essential Supplement Award Winner, 2016, 2014, & 2012

Taste For Life Magazine

Pain Relief Category^†

Delicious Living Supplement Award Winner, 2015 & 2013

Delicious Living Magazine

Pain Category^†

People's Choice Award Winner, 2012

Doctor's Prescription for Healthy Living Magazine

Best Pain-Relieving Product^†

CONTACT: Dean Draznin Communications Dean Draznin dean@drazninpr.com

Office: 641-472-2257 Mobile: 323-397-2647

Diane Chojnowski diane@drazninpr.com Office: 641-209-9591 Mobile: 641-919-0385

Ageless Radiance Skin Nutrition Launched By Terry Naturally

New oral formula shown to improve skin firmness by 55% and radiance by 62%

GREEN BAY, WI, March 9, 2017—EuroPharma, Inc., makers of the Terry Naturallybrand of dietary supplements, has announced the launch of Ageless Radiance™. This product was developed to help improve the appearance of pigmentation, redness, and other imperfections and features L’emerelle™ Complex--a novel nutrient blend developed in France. A clinical study on L’emerelle Complex showed that it improves skin radiance by 62% and skin firmness by 55%. Additionally, the study indicated that the complex:

Evens out skin tone and pigmentation
Reduces dark circles
Fades areas of redness and other imperfections
Revitalizes dull complexion

Ageless Radiance is a proprietary formula that synergistically stimulates the skin’s healthy rejuvenation process. It includes:

French grape seed – bonds with collagen to promote skin resilience and elasticity.
SOD-B– superoxide dismutase from a melon extraction process that robustly protects against free radical damage to the skin.
Zinc citrate and vitamin C – for collagen building and antioxidant properties.

Ageless Radiance combines L’emerelle Complex with a uniquely standardized boswellia and the most clinically studied enhanced absorption curcumin in the world in a complex of turmeric essential oils with turmerones.

“In my opinion, there is nothing more important to skin health and beauty than optimal nutrition. I learned about the L’emerelle Complex on a trip to France, and was very impressed by the amount of improvement shown in clinical studies evaluated by skin experts,” says Terry Lemerond, founder and president of EuroPharma. “I also added our highly effective boswellia and high absorption curcumin with turmeric essential oils (turmerones) to complete the formula. Not only are they potent antioxidants, but their actions in the body stimulate rejuvenating factors that are crucial to skin appearance. ”

Ageless Radiance is now available nationwide at quality health food retailers and integrative pharmacies.

include Curamin, winner of 28 awards for pain relief; CuraMed, containing the most clinically studied enhanced absorption curcumin in the world, with beneficial turmeric oil with turmerones, and the #1 product in its category according to SPINS data; SagaProfor bladder health; Vectomegafull-spectrum omega-3 salmon extract; TraumaplantComfrey Cream; and FastBlockAllergy Relief. The full line of products is available throughout the U.S. in both the health food store and independent pharmacies. At EuroPharma, Our Passion is Your Health™. For more information, visit www.EuroPharmaUSA.com.

CONTACT: Dean Draznin Communications Dean Draznin dean@drazninpr.com

Office: 641-472-2257 Mobile: 323-397-2647

Diane Chojnowski diane@drazninpr.com Office: 641-209-9591 Mobile: 641-919-0385

Cardio-VX1 Launched By Terry Naturally

Proprietary formulation combines nutrients and polyphenols to support heart strength

GREEN BAY, WI, March 9, 2017—EuroPharma, Inc., makers of the Terry Naturallybrand of dietary supplements, has announced the launch of Cardio-VX1™. This product was developed to provide concentrated levels of the most influential heart-healthy ingredients to both fill nutritional gaps in the diet and to promote optimal cardiovascular function.

Combining critical heart nutrients with a uniquely standardized grape seed extract with oligomeric proanthocyanidins (OPCs), the formulation is designed to provide significant cardiovascular benefits.

The healthy heart factors in this formula include:

Magnesium chelate, for healthy heart rhythm and blood pressure levels
Benfotiamine, the fat soluble form of vitamin B1, for healthy circulation, arterial function, and blood vessel support
Pyridoxal-5-phosphate, the methylated form of vitamin B6, which is crucial to the system that transports oxygen to the heart, as well as maintaining fluid balance
French grape seed VX1, uniquely standardized to low molecular weight OPCs for 100% absorbability, this scientifically studied extract is included for healthy blood pressure and cholesterol balance
Pomegranate, to protect against oxidative damage, and support healthy arteries and blood vessel flexibility

“I developed Cardio-VX1 to be a comprehensive formula that addresses all areas of heart function,” says Terry Lemerond, founder and president of EuroPharma. “With all the challenges in our modern world of FrankenFoods and a sedentary lifestyle, strong cardio support becomes even more important. Heart strength and cardiovascular function are a crucial foundation for health, energy, and vitality. ”

Cardio-VX1 is now available nationwide at quality health food retailers and integrative pharmacies.

products is available throughout the U.S. in both the health food store and independent pharmacies. At EuroPharma, Our Passion is Your Health™. For more information, visit www.EuroPharmaUSA.com.

CONTACT: Dean Draznin Communications Dean Draznin dean@drazninpr.com

Office: 641-472-2257 Mobile: 323-397-2647

Diane Chojnowski diane@drazninpr.com Office: 641-209-9591 Mobile: 641-919-0385

Terry Naturally Launches Cold Weather Wellness

Healthy immune system formula features clinically studied ingredients

GREEN BAY, WI, March 9, 2017—EuroPharma, Inc., makers of the Terry Naturallybrand of dietary supplements, has announced the launch of Cold Weather Wellness™—an effective formula for immune support and vitality even in challenging environments.

Cold Weather Wellness delivers clinically studied ingredients that strengthen the body in cold weather. The product combines a trio of standardized herbs: echinacea, which helps the immune system respond to the challenges of winter; andrographis, clinically shown to support lung and respiratory health; and pelargonium, also known as umckaloabo, which lends additional support to the respiratory system and immune strength.

This product provides the right ratio of botanicals to help:

Strengthen immune defenses
Provide sinus and bronchial support
Promote every day resistance

“I have always observed that using a combination of immune supporting ingredients improves outcomes,” states Terry Lemerond, president and founder of EuroPharma, Inc., makers of the Terry Naturally brand. “Cold Weather Wellness is designed to keep you feeling healthy and vigorous, regardless of the weather. It is great for the whole family.”

Terry Naturally’s Cold Weather Wellness is now available nationwide at quality health food retailers and integrative pharmacies.

CONTACT: Dean Draznin Communications Dean Draznin dean@drazninpr.com

Office: 641-472-2257 Mobile: 323-397-2647

Diane Chojnowski diane@drazninpr.com Office: 641-209-9591 Mobile: 641-919-0385

Curamin Enhanced Whey Protein Launched By Terry Naturally

Multipurpose protein and pain relief for every body

GREEN BAY, WI, March 9, 2017—EuroPharma, Inc., makers of the Terry Naturallybrand of dietary supplements, has announced the launch of CuraminEnhanced Whey Protein to provide relief of occasional muscle pain due to exercise or overuse, support healthy weight management (along with diet and exercise), and promote superior physical performance. Curamin is an award-winning supplement for safe and effective pain relief. CuraminEnhanced Whey Protein combines Curamin ingredients with a blend of the concentrate and isolate forms of whey protein that contain the branched chain amino acids (BCAA) needed for superior muscle benefits.

“This product combines all the benefits of Curamin with a blend of high quality whey isolate and concentrate for a full and complete protein source. Whey concentrate metabolizes slowly for sustained benefits and hunger satiation; whey isolate digests quickly for faster absorption and recovery. Whey protein promotes muscle development, which is of course important to athletes, but also crucial to people trying to maintain a healthy weight or to rebuild strength,” says Terry Lemerond, founder and president of EuroPharma, Inc. “This product does not contain any artificial coloring, preservatives, or flavorings and is free of hormones or stimulants. It is safe and effective for the entire family, providing 18 grams of complete protein in a very easy to mix, good tasting formula. It is exciting to offer this formulation as an upgrade for people who want more from their protein supplements.”

Curamin Enhanced Whey Protein was designed to provide a variety of benefits, including:

Pain Relief - Contains superior absorption, clinically studied curcumin and boswellia, along with DLPA and ginger for pain relief.
Exercise Recovery – Less pain and support for healthy muscle tissue reduces recovery time between exertional events.
Sports Performance – These forms of whey protein are easily utilized for energy and stamina, with amino acids to help boost strength and muscle gain.
Weight Management - Improving lean muscle mass helps burn calories more efficiently, and supports satiation to reduce hunger and food cravings.
Promotes Muscle Gain - Whey protein provides powerful building blocks for muscle strength.
Helps Prevent Muscle Loss - Maintaining proper muscle tone helps prevent muscle tissue loss due to aging or inactivity.
Builds Bones - Adequate calcium as part of a healthy diet, along with physical activity, may reduce the risk of osteoporosis in later life.

Curamin Enhanced Whey Protein is now available nationwide at quality health food retailers and integrative pharmacies.

CONTACT: Dean Draznin Communications Dean Draznin dean@drazninpr.com

Office: 641-472-2257 Mobile: 323-397-2647

Diane Chojnowski diane@drazninpr.com Office: 641-209-9591 Mobile: 641-919-0385

Terry Naturally Launches Curamin Headache + Caffeine and Curamin Extra Strength + Caffeine

Curamin family expanded with new enhanced formulas

GREEN BAY, WI, March 9, 2017—Curaminis an award-winning supplement for safe and effective pain relief. † EuroPharma, Inc., makers of the Terry Naturallybrand of dietary supplements, has announced the expansion of the Curamin family of products to incorporate the beneficial properties of caffeine into two new products: Curamin Headache + Caffeine and Curamin Extra Strength + Caffeine.

“Curamin Extra Strength + Caffeine and Curamin Headache + Caffeine target those people for whom caffeine provides additional relief. Caffeine is well known for its pain relieving activity, as well as its ability to improve mood. Additionally, there is a great deal of research on caffeine’s benefits for occasional headaches,” states Terry Lemerond, president and founder of EuroPharma. ††

Both formulas combine the most clinically studied enhanced absorption curcumin in the world, uniquely standardized boswellia, and the amino acid dl-phenylalanine (DLPA) , along with the power of caffeine— about the same amount you’d get in a half cup of coffee in each tablet.

The headache formula also provides the bioactive form of vitamin B6, pyridoxal-5-phosphate (P-5-P) and TRAACSmagnesium glycinate chelate, a better absorbed and utilized form of this crucial mineral.

Magnesium plays an important role in alleviating occasional headaches.

“We decided to create these enhanced formulas because they are a novel approach to relief that you don’t find in other supplements. Most people equate caffeine with energy, and while that is true, it is equally true that it has excellent properties for relieving occasional pain and headaches. There is a segment of the population who experience enhanced pain relief from caffeine. It is my goal to offer our customers a variety of options to better target whatever their specific health needs may be,” states Lemerond.

Curamin Headache + Caffeine and Curamin Extra Strength + Caffeine are now available nationwide at quality health food retailers and integrative pharmacies.

products is available throughout the U.S. in both the health food store and independent pharmacies. At EuroPharma, Our Passion is Your Health™. For more information, visit www.EuroPharmaUSA.com.

^†Occasional muscle pain due to exercise or overuse

^††Occasional headaches due to stress or fatigue

CONTACT: Dean Draznin Communications Dean Draznin dean@drazninpr.com

Office: 641-472-2257 Mobile: 323-397-2647

Diane Chojnowski diane@drazninpr.com Office: 641-209-9591 Mobile: 641-919-0385

Terry Naturally Launches Fibroxia for Both Pain and Fatigue

Clinically studied nutrients combined with essential oils for broader activity

GREEN BAY, WI, March 9, 2017—EuroPharma, Inc., makers of the Terry Naturallybrand of dietary supplements, has announced the launch of Fibroxia.™Fibroxia addresses the physical and emotional aspects of occasional pain with a unique blend of clinically studied botanical ingredients to relieve occasional fatigue and muscle pain related to overuse. This new product offers a powerful combination of the most clinically studied enhanced absorption curcumin in the world, BCM-95 Curcumin, plus a uniquely standardized boswellia with up to ten times more effective compounds (AKBA) than unstandardized products. It also provides concentrated turmeric essential oil, a source of turmerones, and frankincense oil, which deliver important plant compounds that work with both curcumin and boswellia for an elevated level of benefits.

“I designed Fibroxia as the ultimate support for muscle pain, fatigue, and nerve health. It can be used daily for relief of occasional pain, healthy energy, mental well-being, and mobility. When you have occasional exertional pain, it drains your energy and compromises your mood. It makes it difficult to focus. By addressing all 4 elements: occasional muscle pain, fatigue, nerve function, and mental well- being—we can offer more complete relief and restoration of quality of life,” state Terry Lemerond, president and founder of EuroPharma, makers of the Terry Naturally brand of dietary supplements.

“The scientifically studied blend of ingredients in Fibroxia are highly effective for both occasional muscle pain and fatigue, and can make a significant difference in mood as well,” states Jacob Teitelbaum, MD, board certified internist, author and nationally known pain and fatigue expert.

Fibroxia:

Provides relief of occasional muscle pain due to exercise or overuse. Pain can interfere with mobility, focus, positive mood, and energy.
Helps daily energy by supporting proper muscle, brain, and nerve function.
Supports healthy nerve function, which is necessary for proper muscle relaxation, as well as brain and nervous system activity.
Enhances mental clarity by benefitting mood, energy, and focus.

Terry Naturally’s Fibroxia is now available nationwide at quality health food retailers and integrative pharmacies.

CONTACT: Dean Draznin Communications Dean Draznin dean@drazninpr.com

Office: 641-472-2257 Mobile: 323-397-2647

Diane Chojnowski diane@drazninpr.com Office: 641-209-9591 Mobile: 641-919-0385

Terry Naturally Launches O’live

Active olive compounds for heart, brain, skin and more—without the calories

GREEN BAY, WI, March 9, 2017—EuroPharma, Inc., makers of the Terry Naturallybrand of dietary supplements, has announced the launch of O’live™, a proprietary blend of olive leaf, fruit, and fruit oil extracts that provide all of the health benefits of olives (and olive oil) with a fraction of the calories. One softgel (5 calories) delivers the equivalent of two tablespoons of olive oil (120 calories), but without the volume of fat.

“Most people are aware of the tremendous health benefits from olives and olive oil. Among other things, olive compounds support the health of the heart, arteries, and brain; protect sensitive cells from oxidative damage, and promote youthful, resilient skin. However, not everyone consumes olives or olive oil on a daily basis, nor in a large enough quantity, and may be missing out on the powerful health advantages that olives provide,” states Terry Lemerond, president and founder of EuroPharma, makers of the Terry Naturally brand of dietary supplements, “O’live provides the important health compounds from olive oil minus the fat, so it can be utilized more easily by anyone interested in all that olives have to offer.”

O’live delivers the concentrated components of olives and olive oil for full spectrum benefits, including polyphenols, oleuropein, oleanolic acid, maslinic acid, tocopherols (vitamin E), triterpenic compounds, omega-9 fatty acid (oleic acid), and beta-sitosterol. These nutrients promote health and help protect the body from the damaging effects of oxidative stress.

Terry Naturally’s O’live is now available nationwide at quality health food retailers and integrative pharmacies.

28 awards for pain relief; CuraMed, containing the most clinically studied enhanced absorption curcumin in the world, with beneficial turmeric oil with turmerones, and the #1 product in its category according to SPINS data; SagaProfor bladder health; Vectomegafull-spectrum omega-3 salmon extract; TraumaplantComfrey Cream; and FastBlockAllergy Relief. The full line of products is available throughout the U.S. in both the health food store and independent pharmacies. At EuroPharma, Our Passion is Your Health™. For more information, visit www.EuroPharmaUSA.com.

CONTACT: Dean Draznin Communications Dean Draznin dean@drazninpr.com

Office: 641-472-2257 Mobile: 323-397-2647

Diane Chojnowski diane@drazninpr.com Office: 641-209-9591 Mobile: 641-919-0385

Terry Naturally Launches Rhulief Pain Relieving Balm

Over the counter topical medication approved for arthritis pain and more

GREEN BAY, WI, March 9, 2017—EuroPharma, Inc., makers of the Terry Naturallybrand of dietary supplements, has announced the launch of Rhulief™Pain Relieving Balm, an over-the-counter (OTC) topical analgesic for the temporary relief of minor aches and pains of muscles and joints associated with simple backache, arthritis, strains, bruises, and sprains. This novel product combines two OTC medications with approved FDA monographs, camphor and menthol. These medications provide fast and effective relief for:

Arthritis
Sprains
Simple back pain
Bruises
Strains

The active compounds, menthol and camphor, are supplied in a balm of nature-based ingredients that include boswellia, eucalyptus, coconut oil, sesame oil, and beeswax.

“This topical pain relieving balm provides an instant cooling sensation and promotes blood flow to the affected area. Both camphor and menthol are effective for muscle and joint pain, and we combined them for additional benefits. The product is non-GMO and free of parabens and synthetic colors or perfumes. It is safe to use several times a day,” states Terry Lemerond, president and founder of EuroPharma.

Terry Naturally’s Rhulief Pain Relieving Balm is now available nationwide at quality health food retailers and integrative pharmacies.

EuroPharma, Inc., makers of the Terry Naturally brand, offers clinically proven and effective nutritional supplements that improve the health of America. Terry Lemerond, founder and president of EuroPharma, is well-known for innovation, and is credited as the first to introduce glucosamine sulfate and standardized Ginkgo biloba to the U.S. natural products market. Some of our current exclusive products include Curamin, winner of 28 awards for pain relief; CuraMed, containing the most clinically studied enhanced absorption curcumin in the world, with beneficial turmeric oil with turmerones, and the #1 product in its category according to SPINS data; SagaPro for bladder health; Vectomegafull-spectrum omega-3 salmon extract; TraumaplantComfrey Cream; and FastBlockAllergy Relief. The full line of products is available throughout the U.S. in both the health food store and independent pharmacies. At EuroPharma, Our Passion is Your Health™. For more information, visit www.EuroPharmaUSA.com.

CONTACT: Dean Draznin Communications Dean Draznin dean@drazninpr.com

Office: 641-472-2257 Mobile: 323-397-2647

Diane Chojnowski diane@drazninpr.com Office: 641-209-9591 Mobile: 641-919-0385

Terry Naturally Launches Unique Weight Loss Product Slim-VX1

Clinically studied ingredient shown to support 7 times more weight loss

GREEN BAY, WI, March 9, 2017—EuroPharma, Inc., makers of the Terry Naturallybrand of dietary supplements, has announced the launch of Slim-VX1™to support healthy weight loss, in conjunction with a healthy diet and exercise regimen. This product contains a European best-selling innovation available for the first time in the United States—a clinically studied, unique fiber that has been shown to:

Reduce food cravings
Provide a feeling of fullness
Support healthy blood sugar and A1C levels
Boost metabolism
Help reduce fat accumulation
Lower body mass index (BMI)

In a 3 month human clinical study with no dietary restrictions, people taking the concentrated fiber lost up to 7 times the weight of those in the placebo group, who on average gained half of a pound. The 64 individuals in the unique fiber group saw significantly lower BMI (Body Mass Index), body fat, visceral fat (fat accumulated around organs in the torso), and waist, hip, and upper abdominal circumference. An additional significant benefit was that people in fiber group also saw balanced A1C levels, an important parameter of blood sugar health. [Trivedi VR, MC Satia MC, Deschamps A., et al. Nutrition Journal (2016) 15:3]

The proprietary fiber complex is blended with ginger and a French grape seed extract called VX1 that is standardized to contain only low molecular weight polyphenols for 100% absorbability. Both botanicals play a role in healthy metabolism.

“I was very impressed with the success and clinical research on this ingredient when I discovered this best-selling weight loss product in Europe. By combining this clinically studied plant fiber with ginger

and the scientifically studied VX1 French Grape Seed, we can help people better achieve their weight loss goals, and help them maintain a healthy weight,” said Terry Lemerond, president and founder of EuroPharma, “and there are no stimulants or serious side effects with using these compounds from nature.”

Terry Naturally’s Slim VX1 is now available nationwide at quality health food retailers and integrative pharmacies.

Terry Lemerond

Terry Lemerond, founder and president of EuroPharma, Inc.makers of the Terry Naturallyand EuroMedicabrands is passionate about health and nutrition and has owned several health food stores and nutritional manufacturing companies. Prior to EuroPharma, he was the owner/founder of both Enzymatic Therapy, Inc. and PhytoPharmica, Inc.

With more than 40 years in the natural products industry, Terry has researched and developed over 400 nutritional and botanical formulations that continue to be top-selling products in the market today. He is credited as the first to introduce glucosamine sulfate, IP-6, standardized Ginkgo biloba, the concept of botanical standardization and also complex formulations for specific health indications to the U.S. health food market.

Terry shares his wealth of experience and knowledge in health and nutrition through his educational programs, including the Terry Talks Nutrition website, newsletters, podcasts, webinars, and personal speaking engagements. Lemerond is also the author of two books: Seven Keys to Vibrant Health and the recently updated Seven Keys to Unlimited Personal Achievement.

Terry is the host of a weekly radio program. His show, Terry Talks Nutrition, airs locally in Green Bay, Wisconsin and online at www.TerryTalksNutrition.com on Saturday and Sunday mornings at 8:00 a.m. Central Time. Past shows are archived on the Terry Talks Nutrition website.

In early 2015, Terry was named as the first recipient of the American Botanical Council’s Champion Award, created to honor those demonstrating outstanding support of the ABC’s nonprofit educational mission. He was the recipient of the 2013 Southeast Natural Products Association President’s Award, which recognizes those who have made significant lifelong contributions to the natural products industry, as well as the 2010 President's Award by the Natural Products Association Southwest, acknowledging Terry’s years of service and his "love, passion, and generous support for the natural products industry.” In 2008, Terry was honored with the Natural Products Association Industry Champion Award, which recognizes individuals who have made notable contributions above and beyond commercial success.

Today, in addition to leading a thriving natural medicine company, Lemerond continues to lecture on personal and spiritual growth, and conducts educational seminars on the benefits of natural medicines. Terry’s mission is to improve the health of America.

Cheryl Myers, RN

Cheryl Myers, RN is head of scientific affairs and education for EuroPharma, Inc. In this role, Cheryl oversees technical literature development, product research validation, educational outreach, and acts as a liaison with thought leaders in integrative health and natural medicine research.

A recognized expert, Cheryl has been a featured guest on hundreds of radio and television shows. She has been interviewed by the New York Times, Prevention Magazine, and the Wall Street Journal.

As a member of the editorial board of the Natural Medicine Journal (the official journal of the American Naturopathic Association), Cheryl evaluates scholarly articles and studies illuminating the science behind natural health interventions.

Cheryl’s research articles have appeared in diverse publications such as Aesthetic Surgery Journal and Nutrition in Complementary Care: A Dietetic Practice Group of the American Dietetic Association. She has presented a research paper at the North American Menopause Society's annual meeting on herbs for menopause and sleep disorders, and her subsequent paper was presented at the American College of Obstetrics and Gynecology, entitled “Consumer Perception of Healthcare Practitioner Attitude to Black Cohosh for Menopause Symptom Relief.” Her recent Natural Medicine Journal article “Regarding the Effective Treatment of Prediabetes” focused on the role of curcumin in modulating insulin resistance.

As an expert educator on natural medicine, Cheryl has been invited to give educational presentations on various topics at the Mayo Clinic, in Rochester, MN; the Jefferson-Myrna Brind Center of Integrative Medicine at Thomas Jefferson University Hospital, in Philadelphia, PA, and at Florida Hospital Celebration Health.

Cheryl works with a variety of environmental causes, including running a Monarch butterfly rescue program every summer. Cheryl has also been involved in promoting high standards of comfort care in end of life situations and has provided care and counseling to hospice patients.

Jacob Teitelbaum, M.D.

Jacob Teitelbaum, M.D. is a board certified internist and author of the popular free iPhone and Android application “Cures A-Z,” which was ranked in the top 10 of all health/wellness downloads on iTunes. Dr. Teitelbaum is the author of the perennial bestseller From Fatigued to Fantastic! (Avery Penguin), which has sold over half a million copies; Pain Free 1-2-3 (McGraw-Hill); Three Steps to Happiness--Healing Through Joy (Deva Press); the Beat Sugar Addiction Now! series (Fair Winds Press); Real Cause, Real Cure—The 9 root causes of the most common health problems and how to solve them (Rodale Press); The Fatigue and Fibromyalgia Solution (Penguin/Avery); and his latest, The Complete Guide to Beating Sugar Addiction (Fair Winds Press, May 14, 2015).

Dr. Teitelbaum is the lead author of four groundbreaking research studies on effective treatment for Chronic Fatigue Syndrome and Fibromyalgia using an integrated treatment approach called the SHINE Protocol (Sleep, Hormones, Infections/Immunity, Nutrition, Exercise) which showed an average 90% increase in quality of life (p<.0001 vs. placebo). His research on ribose, a unique 5- carbon sugar, showed an average 60% increase in energy at 3 weeks. His work was editorialized in the American Academy of Pain Management, where his integrative SHINE protocol was recognized as standard of practice for fibromyalgia and chronic pain conditions. He is also lead author on a study looking at treating food sensitivities in autism using a desensitization technique called NAET in which 23 of 30 autistic children in the treatment group were able to return to regular school after 1 year vs. 0/30 in the control group.

Dr. Teitelbaum knows CFS/Fibromyalgia as an insider, as he contracted chronic fatigue syndrome when he was in medical school and had to drop out for a year to recover. His web site (www.endfatigue.com) contains a sophisticated computer program that can analyze symptoms and labs to determine the main causes of their fatigue and pain, and create a protocol for optimizing energy tailored to that individual. He also holds the patent for a computerized physician, which collects information from people and creates a complete medical record along with probable diagnoses and recommended treatment to simplify and optimize their care.

Though Dr. Teitelbaum has been a member of the scientific advisory board of EuroPharma since 2010, and lectures on the health benefits of effective natural products, he does not accept any payment for his services. Any royalties earned on products for which he consults with EuroPharma are contributed to various charities, including Vitamin Angels, the American Botanical Council, and the Jacob Teitelbaum Family Foundation for ending world hunger and poverty, creating joy, and empowering people with information on natural therapies.

Ajay Goel, Ph.D.

Ajay Goel, Ph.D., is a Professor and the Director of Translational Genomics and Oncology, and the Director of the Center for Gastrointestinal Research at the Baylor Scott & White Research Institute, Baylor University Medical Center in Dallas, TX. He is one of the top scientists in the world investigating botanical interventions.

Dr. Goel has spent more than 20 years researching cancer and has been the lead author or contributor to over 225 scientific articles published in peer reviewed international journals and several book chapters. He is also the author of the recently published book Curcumin: Nature’s Answer to Cancer and Other Chronic Diseases.

A primary inventor on more than 15 international patents aimed at developing various biomarkers for the diagnosis, prognosis, and

prediction of gastrointestinal cancers, Dr. Goel is currently using advanced genomic and transcriptomic approaches to develop novel DNA- and microRNA- based biomarkers for the early detection of colorectal cancers.

Dr. Goel is currently researching the prevention of gastrointestinal cancers using integrative approaches, including botanical products. Two of the primary botanicals he is investigating are curcumin (from turmeric) and boswellia. He has also published a study on grape seed extract. Dr. Goel is a member of the American Association for Cancer Research and the American Gastroenterology Association, and is on the international editorial boards of Gastroenterology, Clinical Cancer Research, Carcinogenesis, PLoS ONE, Digestive Diseases and Sciences, Scientific Reports, Epigenomics, Future Medicine, Alternative Therapies in Health and Medicine, and World Journal of Gastroenterology. He also serves on various grant funding committees for the National Institutes of Health (NIH) and several international organizations.

He has been an invited speaker at Harvard Medical School and other universities and conferences around the world, and served as a visiting professor at the Department of Medicine at the University of Illinois at Chicago; Panjab University, India; Medical University of Vienna, Austria; and at Yonsei University School of Medicine, Seoul, Korea. His many awards include the Union of European Gastroenterology Federations “Distinguished Researcher” Award and numerous “Poster of Distinction” awards from the American Gastroenterological Association.

Dr. Goel is a big supporter of the movement for more simple, natural foods and improved dietary practice, especially for our children. “Our children are building bodies that need to last a hundred years or maybe even more. It is our responsibility to provide them with the healthiest, purest building blocks available: wholesome, natural food.” He also works privately with an organization in India to provide food, shelter, education, and care for children who have lost their parents and are left orphaned.

Holly Lucille, ND, RN

Holly Lucille, ND, RN, is a nationally recognized and licensed naturopathic doctor, educator, natural products consultant, and television and radio host. She is also the author of several books including Creating and Maintaining Balance: A Women’s Guide to Safe, Natural, Hormone Health and The Healing Power of Trauma Comfrey.

An acclaimed expert in the field of integrative medicine, Dr. Lucille lectures throughout the nation on a variety of natural health topics. Her appearances include national media programs and networks including Dr. Oz and The Doctors.

She is on the editorial advisory board of Alternative Medicine and Natural Practitioner and is also regularly quoted as an expert in

both consumer and peer journals. In 2007, Dr. Holly was listed in Time Magazine’s “Alt List” as one of the “Top 100 Most Influential People.” In 2012 she launched her own talk show, “Myth- Defying with Dr. Holly” on the Z Living network and is currently the host of “Inherently You”: on RadioMD.

She is currently the chairwoman of the Natural Partners INC. advisory board and on the board of directors of the Institute for Natural Medicine. As the past president of the California Naturopathic Doctors Association she worked to ensure the availability of safe naturopathic health care by spearheading a lobbying effort to have naturopathic doctors licensed in the state of California. She was awarded the “SCNM Legacy Award” for her “contribution to the advancement and development of the field of naturopathic medicine.”

Dr. Lucille believes in the science, art, and mystery of healing and has a heartfelt passion for the individual wellness of all people. Built on this foundational belief, she uses the magnificence of multiple media platforms to truly make a difference and empower people to heal. Her private practice in Los Angeles, Healing from Within Healthcare, focuses on comprehensive naturopathic medicine and individualized care.

Dr. Holly graduated from the Southwest College of Naturopathic Medicine in Tempe, AZ, where she received the prestigious “Daphne Blayden Award” for her “commitment to naturopathic medicine, academic excellence, compassion, perseverance, a loving sense of humor and a positive, supportive outlook.”

In her “off time” Dr. Holly enjoys being with her family, two- and four-legged, playing the bass guitar, tending to her hydroponic garden, and riding her motorcycle through the mountains and along the beaches of Los Angeles.

Gaetano Morello, N.D.

Gaetano A. Morello, N.D., is regarded as a leading authority on natural medicine. A graduate of the prestigious Bastyr University, and a board- certified naturopathic physician, he is the author of The Cleanse, Ultimate Inside Out Approach, Whole Body Cleansing, and a contributing author to A Textbook of Natural Medicine, the most definitive text on natural medicine in the world.

Dr. Morello lectures extensively to doctors, pharmacists, health food store personnel and the lay public about the benefits of natural medicine. His knowledge and experience in the clinical applications of the scientific foundations of natural medicine have placed him in demand as a speaker and increasingly as a contributor to health and medical panels, directorships, forums and conventions throughout the world.

He has written hundreds of articles and has given over 500 medical presentations, in the United States, Canada, Australia, Germany and Italy in the last decade. He is a known authority on a wide variety of health topics such as: complex chronic diseases (fibromyalgia, chronic fatigue syndrome, ME, Lyme disease,) cardiovascular disease, pain management, detoxification, digestion and much more.

He is member of the Quality Assurance Committee for the College of Naturopathic Physicians of British Columbia. Dr. Morello’s mission is to ensure that Naturopathic Medicine utilizes the highest level of quality care for all patients.

Besides his own busy private practice, Dr. Morello is a clinician at the celebrated Complex Chronic Disease Program at BC Women's Hospital in Vancouver, treating chronic fatigue syndrome, fibromyalgia, ME and Lyme disease. He is the first naturopathic physician to hold such a position at a major North American hospital.

Always an advocate of early childhood nutrition, Dr. Morello and his wife, Karlene, support a variety of healthy food initiatives in both Canada and the United States.

Alexander George Panossian, PH.D., Dr. Sci.

Alexander George Panossian, PH.D., Dr. Sci., is a noted international herbal expert, completed his doctorate in organic chemistry at the Yerevan State University and obtained his scientific degrees from Moscow's Institute of Bioorganic Chemistry and Institute of Fine Chemical Technology.

In Armenia, he worked for the National Academy of Sciences and the National Institute of Health. After the collapse of United Soviet Socialist Republics (USSR), Dr. Panossian was made a full professor of chemistry of natural and physiological active compounds in the Russian Federation. In 2003, he moved to Sweden where he worked for the Swedish Herbal Institute as head of research and development. During his scientific career,

he was a guest scientist in the laboratory of Nobel Laureate Bengt Samuelsson at the Karolinska Institute in Stockholm, at Munich University, and at King's College in London. He has written or co-authored more than 170 articles in peer-reviewed journals.

Alexander Panossian is an advisory board member of the American Botanical Council (ABC) and also the Editor-in-Chief of Phytomedicine, International Journal of Phytopharmacology and Phytotherapy (Elsevier, Germany).

Published Studies on Curcumin (BCM-95)

1.Efficacy of curcumin, and a saffron/curcumin combination for the treatment of major depression: A randomised, double-blind, placebo-controlled study. the thespice havebeen poordesigns, sizes, the of are a double-blind, 123 individuals to oneof low-dose mg mg combined plus mgb.i.d.)12 outcome theSymptomatology (IDS-SR30) AnxietyInventory(STAI). drug in to superior in <.001) Activedrug efficacyin to theof of65%versus 35% the ofcurcumin orthe combination. samplesizes to examinetheefficacyofdifferingof in in drugdifferingdoses of werein in Drummond Efficacyof a the ofmajor A double-blind, Journal of Affective Disorders

Curcumin and cognition: a randomised, placebo-controlled, double-blind study of community-dwelling older adults. Curcumin therapy in animals has produced positive cognitive and behavioural outcomes; results of human trials, however, have been inconsistent. In this study, we report the results of a 12-month, randomised, placebo- controlled, double-blind study that investigated the ability of a curcumin formulation to prevent cognitive decline in a population of community-dwelling older adults. Individuals (n

96) ingested either placebo or 1500 mg/d BiocurcumaxTM for 12 months. A battery of clinical and cognitive measures was administered at baseline and at the 6-month and 12- month follow-up assessments. A significant timetreatment group interaction was observed for the Montreal Cognitive Assessment (repeated-measures analysis; timetreatment; F=385, P<005). Subsequent analysis revealed that this association was driven by a decline in function of the placebo group at 6 months that was not observed in the curcumin treatment group. No differences were observed between the groups for all other clinical and cognitive measures. Our findings suggest that further longitudinal assessment is required to investigate changes in cognitive outcome measures, ideally in conjunction with biological markers of neurodegeneration. [Rainey-Smith SR, Brown BM, Sohrabi HR, Shah T, Goozee KG, Gupta VB, Martins RN. Curcumin and cognition: a randomised, placebo-controlled,

10/18/2016

double-blind study of community-dwelling older adults. Br J Nutr. 2016 Apr 22:1-8 (Epub ahead of print.)]

3.Effect of Curcumin Supplementation During Radiotherapy on Oxidative Status of Patients with Prostate Cancer: A Double Blinded, Randomized, Placebo-Controlled Study. is both ofthe studywas to the ofcurcumin on of with Fortypatients radiotherapyprostateto the n =20)or (PG, n = They during therapyofup to 74 antioxidant (TAC) activitysuperoxide peroxidase(GPx) baseline 3 mo radiotherapy ofwas to the the PSA were <0.001) theactivity =0.018)radiotherapy those however, theactivity a reduction =0.026) had a increase(P =0.014) thosein PG. PSA to 0.2 in both 3mo no the2 outcomes. R, Molana G ofCurcumin RadiotherapyonOxidative of A Randomized,

Placebo-Controlled Study. Nutrition and Cancer. 2016;0(0):1-9.]

Curcumin and Major Depression: A Randomised, Double-blind, Placebo Controlled Trial Investigating the Potential of Peripheral Biomarkers to Predict Treatment Response and Antidepressant Mechanisms of Change. This trial provided partial support for the efficacy of supplementation with a patented curcumin extract (500 mg, twice daily BCM-95 Curcumin) for 8 weeks in reducing depressive symptoms in people with major depressive disorder. In the present paper, a secondary, exploratory analysis of salivary, urinary and blood biomarkers collected during this study was conducted to identify potential antidepressant mechanisms of action of curcumin. Pre and post-intervention samples were provided by 50 participants diagnosed with major depressive disorder, and the Inventory of Depressive Symptomatology self-rated version (IDS-SR30) was used as the primary depression outcome measure. Compared to placebo, 8 weeks of curcumin supplementation was associated with elevations in urinary thromboxane B2 (p <.05), and substance P (p

<001); while placebo supplementation was associated with reductions in aldosterone (p <05) and cortisol (p <05). Higher baseline plasma endothelin-1 (rs=−.587; p <01) and leptin (rs=−.470; p <05) in curcumin-treated individuals was associated with greater reductions in IDS-SR30 score after 8 weeks of treatment. Our findings demonstrate that curcumin supplementation influences several biomarkers that may be associated with its antidepressant mechanisms of action. Plasma concentrations of leptin and endothelin-1 seem to have particular relevance to treatment outcome. Further investigations using larger samples sizes are required to elucidate these findings, as the multiple statistical comparisons completed in this study increased the risk of type I errors. [Lopresti AL, Maes M, Maker GL, Hood S, Drummond PD. Curcumin and major depression: A randomised, double-blind, placebo-controlled trial investigating the potential of peripheral biomarkers to predict

10/18/2016

treatment response and antidepressant mechanisms of change. European Neuropsychopharmacology. Dec. 5, 2014]

5.Curcumin for the Treatment of Major Depression: A Randomised, Double-blind, Placebo Controlled Study. this 56 individuals twiceor8 primary theof outcomes AnxietyInventory(STAI). baselineto 4, both in most secondary 4to 8, more in several symptoms, ax mood a STAItrait to in depressive occurring 4 to 8 efficacy in a AL, M, Maker Hood S, the ofmajor A blind, J Affect Disord.

6.A Pilot Clinical Trial of Radioprotective Effects of Curcumin Supplementation in Patients with Prostate Cancer. prostatereceivingradiation therapyusuallyseveral side thesetoxicities dose ofthis to the ofBCM-95 in Fortypatients radiotherapywererandomly to taking3 500 of n=20), or ofwas to radiotherapy the symptoms. changein urinarysymptoms the period betweenp patients in the milderurinarysymptoms the in patients therapy reducingtheseverityofradiotherapyurinarysymptoms. R, MolanaS, Apilot of of in J Cancer Sci Ther.

A Randomized, Pilot Study to Assess the Efficacy and Safety of Curcumin in Patients with Active Rheumatoid Arthritis. In this study, 45 patients with rheumatoid arthritis were randomized into 3 groups, with patients receiving either BCM-95 curcumin 500 mg twice daily, the prescription drug diclofenac sodium (one brand name is Voltaren) 50 mg twice daily, or a combination of the two. The results were judged using the clinically validated Disease Activity Score (DAS) 28 and also with the American College of Rheumatology

(ACR) criteria and scores for pain and swelling in joints. Patients in all 3 groups improved. The curcumin group showed the greatest improvement, and the endpoint scores were significantly better than the patients in the drug group. Using both interventions concurrently did not show any additional benefit with regards to disease scores. Curcumin was found to be safe with no adverse effects in this study. In the drug group. 14% of the

10/18/2016

patients withdrew because of adverse effects. [Chandran B, Goel A. A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis. Phytother Res. 2012 Nov;26(11):1719-25.]

Randomized, Controlled Human Clinical Study to Assess the Efficacy and Safety of BCM-95& BospureCompared to Celecoxib in the Management of Knee Osteoarthritis. Originally presented at the Osteoarthritis Research Symposium Internationale (OARSI) Annual World Congress on Osteoarthritis, September 15-18, 2011. San Diego, CA. 28 subjects with diagnosed osteoarthritis of the knee were randomized to a 500 mg blend BCM-95 curcumin and Bospure Boswellia twice a day or to the prescription

drug celecoxib (one brand name is Celebrex) 100 mg twice a day. Symptom scoring and clinical evaluation yielded superior results on pain relief and distance walked for the BCM- 95 and Bospure blend compared to celecoxib. BCM-95 and Bospure equaled celecoxib on joint flexibility. No serious adverse effects noted. [Kizhakedath R, Antony B, Benny M, Kuruvilla BT. Clinical evaluation of a herbal product (Rhulief™) in the management of knee osteoarthritis. Abstract 316. Osteoarthritis Cartilage. 2011;19(S1):S145-S146.]

9.Efficacy and Safety of Curcumin in Major Depressive Disorder: A Randomized Controlled Trial. of activityin ofthis to theefficacy safetyof fluoxetinein disorder 60 in a1:1:1 six treatment fluoxetine individually primaryefficacy accordingto Hamilton Rating secondaryefficacyvariable thechangein scoresix We the proportion of the inthe (77.8%) inthefluoxetineand the (62.5%) thesedatanot (P= the changein the ofsix in three study may safemodalityin orpsychotic Goel Efficacy safetyof in a Phytother Res.

10.Comparative Study of the Efficacy of Curcumin and Turmeric as Chemopreventative Agents in Oral Submucous Fibrosis: A Clinical and Histopathological Evaluation. is achronicdiseaseofthe a progression to The ofthis studywasto if oil ofthetissue to oral were to 3 of16 onereceived 1 of 500 mgcurcuminioids, 2 of oil, in themouthdaily of600 the twice oil oral Thestudy 6 months, were in

disease scores for both group 1 and 2 at each measurement. The authors reported “remarkable improvements after only the first 15 days of use.” After 6 months of use, 7 of the 16 participants in the placebo group were in the advanced disease stage (meaning closer to malignancy) compared to only 1 person in the BCM-95 curcumin group. No serious adverse effects were noted, and the authors called for more and larger trials, as this holds good promise for treatment of OSMF in the future.” [Deepa Das A, Balan A, Sreelatha KT. Comparative study of the efficacy of curcumin and turmeric as chemopreventative agents in oral submucous fibrosis: a clinical and histopathological evaluation. JIAOMR; April-June 2010;22(2):88-92.]

11.Human Clinical Study to Evaluate the Bioavailability of BCM-95. 15 healthymen 8 to and 7 to 12 peak 1600 above200 12 200 ng/g than 2 are10-fold [BennyM, Antony of . Spice India

12.A Pilot Cross-Over Study to Evaluate Human Oral Bioavailability of BCM-95, A Novel Bioenhanced Preparation of Curcumin. study BCM-95 in to and to pepper lecithin. results 7 700%) plain curcumin, onetimepoint, ablood 10 of 6.3 630%) lecithin. [Antony Apilot studyto oral bioavailabilityof anovel of Ind J Pharm Sci. 2008

13.Six-Month Randomized Placebo-Controlled, Double-Blind, Pilot Clinical Trial of Curcumin in Patients with Alzheimer’s Disease. 34 randomized to1 4 orplacebo. overage50, a oforpossible ontheof Communicative Related Some serum of beta, ofoxidativestress) antioxidant 1 4 oxidative antioxidant more in the than in 1gor4 g There a increasein betain both 1 g 4g but not this “possibly of to beta in the the beta CW, pilot of in J Clin Psychopharmacol. 2008

Curcumin Effects on Blood Lipid profile in a 6-month Human Study. No significant cholesterol lowering effects found, though authors speculate curcumin has other cardioprotective physiological effects. [Baum L, Cheung SK, Mok VC, et al. Curcumin effects on blood lipid profile in a 6-month human study. Pharmacol Res. 2007 Dec;56(6):509-14.]

15.Oral Bioavailability of BCM-95in Dogs study specifically in veterinarypurposes. Sixhealthy theveterinary BCM-95 approximately7-foldin over 8 approximately when for12 [Antony DW.anovel, preparation in 2009 2009;

16.Effect of Citrus Polyphenol- and Curcumin-supplemented Diet on Inflammatory State in Obese Cats. studylooking pro-inflammatorystatein of on inflammatory safeusein impact on 2 reduction of (liverto is liver to morelike in [Leray Jeusette C, P. on statein cats. Br J Nutr. 2011 Suppl

17.Chemoprevention and Treatment Efficacy of Curcumin in Combination with Metformin in an in Vivo Oral Carcinogenesis Model. oftheefficacyof in of lesion using the into control the which thecausing 17 thetaken the into 4 1 arm 2 3 the arm 4 a ofboth 17th theend ofthe25 study samples Theaveragetumorvolume in the and the 2.45; 1.450.33) to the4NQOarm average tumors)mousewas in the (Avg0.375) the (Avg0.25) to thearm (Avg ofthecombination better to in the tumor both on its in thecombination is in chemoprevention. usingthe subsequent currently [Siddappa S, Efficacyof in in in

Model. 5th International Federation of Head and Neck Oncologic Societies (IFHNOS). July 26th-30th2014, New York, NY. Also presented at the 13th National Conference of Foundation for Head and Neck Oncology (FHNO). September 27th – 29th 2013, JAIPUR.]

Evaluation of Antidepressant Like Activity of Curcumin and its Combination with Fluoxetine and Imipramine: an Acute and Chronic Study. In animal model of depression, BCM-95 curcumin is compared to generic fluoxetine (one brand name is Prozac) and imipramine (one brand name is Tofranil). BCM-95 curcumin performed as

well as either prescription anti-depressant drug on all measures of depression. However, adding BCM-95 curcumin to the prescription drugs did not increase antidepressant effects. [Sanmukhani J, et al. Evaluation of antidepressant like activity of curcumin and its combination with fluoxetine and imipramine: an acute and chronic study. Acta Pol Pharm. 2011 Sep-Oct;68(5):769-75.]

19.The Effect of Exercise and Nutritional Supplementation on Proinflammatory Cytokine Expression in Young Racehorses During Training. responseto exercise themild of to joint, thereisa deal of ontheinflammatoryresponseto in is regardingtheresponseto intrainingracing we theresponseto in a of during thereis in to control or the ofa

[containing BCM-95curcumin, BosPureboswellia, coenzyme Q10, glycine proprionyl-L- carnitine HCl, and D-ribose] fed to half of the horses undergoing training. Twenty-five Thoroughbred horses aged 2 years were followed through their initial race training.

Peripheral blood samples were collected at various times during the exercise for the quantitation of lactic acid, oxidative stress, and inflammatory cytokine gene expression. There was an intensity-dependent effect of exercise on lactate, malondialdehyde, and proinflammatory cytokine gene expression. Although training itself was associated with an overall reduction in inflammatory markers, horses receiving the supplement exhibited further reductions in their indicators of inflammation. As such, this study provides novel evidence of nutritional supplementation reducing postexercise inflammation. [Horohov DW, Sinatra ST, Chopra RK, Jankowitz S, Betancourt A, Bloomer RJ. The effect of exercise and nutritional supplementation on proinflammatory cytokine expression in young racehorses during training. J Equine Vet Sci. 2012 December;32(12):805-15.]

20.Comparative Bioavailability of Curcumin, Turmeric, and Biocurcumax™ in Traditional Vehicles using Non-Everted Rat Intestinal Sac Model. of using a rat of showed in thepermeabilityof in lipophilicityofthevehicle Maximum of was oil milk aqueous in 8 h. very important that theof was from strongly beconsumed inlipophilic of formaximum [Shishu MM.bioavailabilityof in usingnon-everted model. J Funct Foods

Evaluation of Antiepileptic and Memory Retention Activity of Curcumin Per SE and in Combination with Antiepileptic Drugs. Antiepileptic activity of curcumin and its combination with phenytoin and sodium valproate were studied in chronic model (14 days) of Maximal Electroshock Seizure (MES) and Pentylenetetrazole (PTZ) induced seizure

10/18/2016

respectively. Elevated plus maze test was used to study effect of drugs and/or seizures on memory retention in MES and PTZ groups. Curcumin in both doses did not show any significant effect (P = 0.33) on tonic extension, while curcumin 100 mg/kg significantly (P

< 0.01) reduced clonic phase compared to vehicle control. Curcumin in 100 mg/kg dose significantly (P < 0.001) inhibited PTZ induced seizure. Addition of curcumin to sub therapeutic dose of sodium valproate showed synergistic effect. Curcumin did not show any effect on memory retention. Inhibition of PTZ induced seizure by curcumin could be due to effect on γ-amino butyric acid receptor (GABA) pathway and its antioxidant property.

Curcumin can be effective in absence seizure alone and as add on with sodium valproate. [Anovadiya AP, Sanmukhani JJ, Vadgama VK, Tripathi CB. Asian J Pharm Clin Res.

2013;6(2):145-148.]

Systematic and comprehensive investigation of the toxicity of curcuminoid-essential oil complex: A bioavailable turmeric formulation. Curcumin, the active component present in Curcuma longa of the family Zingiberaceae, has a number of pharmacological effects, including potential anti‑inflammatory activity. One of the major limitations of curcumin/turmeric extract is its poor absorption through the gastrointestinal tract. Several approaches have been adopted to increase the bioavailability of curcumin, including loading

curcumin into liposomes or nanoparticles, complexation with phospholipids, addition of essential oils and synthesizing structural analogues of curcumin. In the present study, the toxicity and safety of one such bioavailable turmeric formulation, curcuminoid‑essential oil complex (CEC), the toxicity profile of which has not been reported, were examined using in vivo and in vitro models, as per the guidelines of the Organisation for Economic Co-

operation and Development. Investigations of acute toxicity study were performed in rats and mice, and the results revealed no signs and symptoms or toxicity or mortality in any of the animals at the maximum recommended dose level of 5,000 mg/kg body weight. The repeated administration of CEC for 90 days in Wistar rats at a dose of 1,000 mg/kg body weight did not induce any observable toxic effects, compared with corresponding control animals. Mutagenicity/genotoxicity investigations were also performed using a bacterial reverse mutation assay (Ames test), a mammalian bone marrow chromosome aberration test

and a mammalian erythrocyte micronucleus test in mice. CEC was found to be non‑

mutagenic in all three mutagenic investigations. Consequently, the present study indicated that CEC elicited no toxic effects in animals or in vitro. Therefore, following investigations of acute toxicity, repeated dose toxicity and mutagenicity, CEC was deemed a safe, non‑ toxic pharmacological formulation. [Aggarwal ML, Chacko KM, Kuruvilla BT. Systematic

and comprehensive investigation of the toxicity of curcuminoid-essential oil complex: A bioavailable turmeric formulation. Molecular Medicine Reports. 2016;13:592-604. DOI: 10.3892/mmr.2015.4579.]

Curcumin mediates chemosensitization to 5-fluorouracil through miRNA-induced suppression of epithelial-to-mesenchymal transition in chemoresistant colorectal cancer. Resistance to cytotoxic chemotherapy is a major cause of mortality in colorectal cancer (CRC) patients. Chemoresistance has been linked primarily to a subset of cancer cells undergoing epithelial-mesenchymal transition (EMT). Curcumin, a botanical with anti- tumorigenic properties, has been shown to enhance sensitivity of cancer cells to chemotherapeutic drugs, but the molecular mechanisms underlying this phenomenon remain unclear. Effects of curcumin and 5-fluorouracil (5FU) individually, and in combination, were examined in parental and 5FU resistant (5FUR) cell lines. We performed a series of

10/18/2016

growth proliferation and apoptosis assays in 2D and 3D cell cultures. Furthermore, we identified and analyzed the expression pattern of a subset of putative EMT-suppressive microRNAs (miRNAs) and their downstream target genes regulated by curcumin.

Chemosensitizing effects of curcumin were validated in a xenograft mouse model. Combined treatment with curcumin and 5FU enhanced cellular apoptosis and inhibited proliferation in both parental and 5FUR cells, while 5FU alone was ineffective in 5FUR cells. A group of EMT-suppressive miRNAs were upregulated by curcumin treatment in 5FUR cells. Curcumin suppressed EMT in 5FUR cells by downregulating BMI1, SUZ12 and EZH2 transcripts, key mediators of cancer stemness-related polycomb repressive complex subunits. Using a xenograft and mathematical models we further demonstrated that curcumin sensitized 5FU to suppress tumor growth. We provide novel mechanistic evidence for curcuminmediated sensitization to 5FU-related chemoresistance through suppression of EMT in 5FUR cells via upregulation of EMT-suppressive miRNAs. This study highlights the potential therapeutic usefulness of curcumin as an adjunct in patients with chemoresistant advanced CRC. [Toden S, Okugawa Y, Jascur T, Wodarz D, Komarova NL, Buhrmann C, Shakibaei M, Boland, Goel A. Curcumin mediates chemsensitization to 5- fluorouracil through miRNA-induced suppression of epithelial-to-mesenchymal transition in chemoresistant colorectal cancer. Carcinogenesis. 2015 Feb 4 (Epub ahead of print).]

24.BCM-95 Curcumin Improves Efficacy of Chemotherapy 5-Fluorouracil in Chemoresistant Colorectal Cancer. More15%of cancer to and tumor as 50-60%. Cancer ofsurviving of This study the of in context ofCSC activityin 3D ofCRC the ofon in to of inhibiting Curcumin strongly CRC in density MMR- CRC These of in enhancingto supported its abilityto effectively CSCpools decreased CSC positivecells. previously of in toon DNA theCSC M, C, KraeheP P, C Goel Curcumin in densityPLoS ONE

25.Curcumin suppresses crosstalk between colon cancer stem cells and stromal fibroblasts in the tumor microenvironment: potential role of EMT. of and tumor adynamicin and this we the the of especiallyon cancer in amodel invivo tumor Colon and in aorhigh densitytumor in Results: tumor

co-cultures supported intensive crosstalk between cancer cells and fibroblasts and enhanced up-regulation of metastatic active adhesion molecules (b1-integrin, ICAM-1), transforming growth factor-b signaling molecules (TGF-b3, p-Smad2), proliferation associated proteins (cyclin D1, Ki-67) and epithelial-to-mesenchymal transition (EMT) factor (vimentin) in HCT116 compared with tumor mono-cultures. High density tumor microenvironment co- cultures synergistically increased tumor-promoting factors (NF-kB, MMP-13), TGF-b3, favored CSC survival (characterized by up-regulation of CD133, CD44, ALDH1) and EMT- factors (increased vimentin and Slug, decreased E-cadherin) in HCT116 compared with high density HCT116 mono-cultures. Interestingly, this synergistic crosstalk was even more pronounced in the presence of 5-FU, but dramatically decreased in the presence of curcumin, inducing biochemical changes to mesenchymal-epithelial transition (MET), thereby sensitizing CSCs to 5-FU treatment. Conclusion: Enrichment of CSCs, remarkable activation of tumor-promoting factors and EMT in high density co-culture highlights that the crosstalk in the tumor microenvironment plays an essential role in tumor development and progression, and this interaction appears to be mediated at least in part by TGF-b and EMT. Modulation of this synergistic crosstalk by curcumin might be a potential therapy for CRC and suppress metastasis. [Buhrmann C, Kraehe P, Lueders C, Shayan P, Goel A, Shakibaei M. Curcumin suppresses crosstalk between colon cancer stem cells and stromal fibroblasts in the tumor microenvironment: potential role of EMT. PLoS ONE. 2014;9(9): e107514.]

26.Novel evidence for curcumin and boswellic acid induced chemoprevention through regulation of miR-34a and miR-27a in colorectal cancer. is oneofthemost ofmortality butit is trulyaBoth boswellic are dietary been multiple datasuggest the ofthese in be regulation ofkey Here, the of 3 on of miRNAs in CRC in vivo usinga mouse and cell in CRC enhanced with that regulatory in-silico regulatorysignaling modulators of We of ofmiR-27ain CRC we in amousexenograft both tumor in theof miR-27a, ourin vitro provideforthe of of in S, C, M, CR, Cancer Prev Res (Phila). 2015 23.(Epub of

27.Curcumin potentiates antitumor activity of 5-fluorouracil in a 3D alginate tumor microenvironment of colorectal cancer. the of 3D thetumor invivo attention. we 3D forof5-fluorouracil or/and on malignancyof cancer on of cell its in atumor CRC into in a invaded from During of in 3 ofcells, (2) (3)adherent (CXCR4, werein the invasive to theadherent in to the an inmalignancy capacity and sensitivityto of to the to was 8nM, but

5 μM curcumin significantly reduced 5-FU concentrations in HCT116 and HCT116R cells (0.8nM, 0.1nM, respectively) and these effects were accompanied by down-regulation of NF-κB activation and NF-κB-regulated gene products. CONCLUSIONS: Our results demonstrate that the alginate provides an excellent tumor microenvironment and indicate that curcumin potentiates and chemosensitizes HCT116R cells to 5-FU-based chemotherapy that may be useful for the treatment of CRC and to overcome drug resistance. [Shakibaei M, Kraehe P, Popper B, Shayan P, Goel A, Buhrmann C. Curcumin potentiates antitumor activity of 5-flurouracil in a 3D alginate tumor microenvironment of colorectal cancer. BMC Cancer. 2015 Apr 10;15:250.]

28.BCM-95 and (2-hydroxypropyl)-β-cyclodextrin reverse autophagy dysfunction and deplete store lipids in Sap C-deficient fibroblasts. C deficiencyis a of C or ofand lipids inthe therapies arecurrentlythe of C Wepreviously aamount activityof (Cath)B Cath defectiveautophagyoccur theuseof acurcumin to function of C- increaseofthe ofCath B clearanceof and in lysosomes. We enhance promotingcapacity anovel approach to C to secondary in this M, M, S, S, M, R. autophagydysfunction storelipids in Hum Mol Genet. 2015 Aug

29.Curcumin inhibits cancer-associated fibroblast-driven prostate cancer invasion through MAOA/mTOR/HIF-1α signaling. are in the of supporting to in tumor of recentlybeen found to viaits onavariety in this could cancer monoamineoxidaseA of exploits to amigratory prostate was to 4 receptor in inhibited in inhibiting therebysupportingtheeffect of in [Du Zhang Shi Guan Wang inhibits prostate through International Journal of Oncology

30.Curcumin inhibits polycomb repressive complex 2 through lncRNA-PVT1 and enhances gemcitabine sensitivity in chemoresistant pancreatic cancer. is oneofthemost a mortalityis ofto Curcumin is a its overcomede-novo polycomb 2 tobe in with longnon-coding dataprovidepreviouslyunrecognized for to ofPRC2 in thepotential in [Yoshida S, WengW, C, CR, inhibits complex2 sensitivityin 2016;

Additional Supporting Studies

31.The Role of Curcumin Administration in Patients with Major Depressive Disorder: Mini Meta-Analysis of Clinical Trials. is a disease negatively thequalityof therisk of demonstrated the substanceofthe ofthis is to the of in Weextensively theuntil 2015. model tothepooled ofmeans toexaminethe of study on the Six the a

significantly higher reduction in depression symptoms [SMD = -0.34; 95% confidence interval (CI) = -0.56, -0.13; p = 0.002]. Subgroup analyses showed that curcumin had the highest effect when given to middle-aged patients (SMD = -0.36; 95% CI = -0.59; -0.13; p = 0.002), for longer duration of administration (SMD = -0.40; 95% CI = -0.64, -0.16; p = 0.001), and at higher doses (SMD = -0.36; 95% CI = -0.59, -0.13; p = 0.002). The administration of new formulation of curcumin (BCM-95) had non-significantly higher effect on depression as compared with the conventional curcumin-piperine formula. We conclude that there is supporting evidence that curcumin administration reduces depressive symptoms in patients with major depression. [Al-Karawi D, Al Mamoori DA, Tayyar Y. The Role of Curcumin Administration in Patients with Major Depressive Disorder: Mini Meta-Analysis of Clinical Trials. Phytother Res. 2015 Nov 27. doi: 10.1002/ptr.5524. (Epub ahead of print).]

32.The efficacy and safety of using CartiJoint Forte (a combination of glucosamine hydrochloride, chondroitin sulfate and bio-curcumin) with exercise in the treatment of knee osteoarthritis: a randomized, double blind, placebo-controlled study. to delay one Adietary CartiJoint onchondroitin in this assessefficacysafetyofCartiJoint therapyin subjects A randomized, doubleblind, to theRehabilitation of randomly to oracontrol two of 8 thosein the a subjects out duringthecourseofthe both 20 of therapyduringthethe Primary both moving' usingtheAsecondarywas ofkneefunction Each was out baseline 8 (T1) 12 to be (F=13.712; no groups moving' a x ofon p=.0001). most in the 8 p=.045). p=.0001), the presented ascore (F=7.091; in thekneeROM added to to in patients. of Curcuminoids plus to improves moving' [Sterzi S., efficacy safetyusingCartiJoint (a of chondroitin bio-curcumin) in the ofknee

osteoarthritis: a randomized, double blind, placebo-controlled study. Eur J Phys Rehabil Med. 2016 Mar 3 (Epub ahead of print).]

Research Information on Comfrey Cream

(Symphytum x uplandicum NYMAN)

PUBLISHED STUDIES:

Randomized double-blind study: wound-healing effects of a Symphytum herb extract cream. Symphytumuplandicum Nyman) in children.

Abstract: The wound healing effects of the topically applied preparation Traumaplant containing a concentrate (10% active ingredient) from the aerial parts of medicinal comfrey (Symphytum uplandicum Nyman) were examined in a randomized, controlled, clinical double- blind study. An otherwise identical low-dose preparation (1% active ingredient) was used as a control. The study population consisted of 108 children aged 3-12 years (n=54/group) with fresh abrasions. A 50% healing rate was reached 0.9 days earlier with the higher than with the lower concentration cream. The difference in the healing rate (0.380.18/day [95% CI 0.33-0.4] vs.

0.260.14/day [95% CI 0.222-0.297]) was statistically significant (p=0.0002). Physicians and children/parents both rated the efficacy of the 10% cream as significantly better than that of the control preparation (physicians' assessment after 2-3 and 7-9 days for verum vs. control: 90.7 and 92.6% vs. 55.6 and 74.0% of the healing rates were rated as "good" or "very good", respectively; p=0.0004 and 0.01). In subgroup analyses, there was no significant influence on the healing rate of the time elapsed between the accident and the first consultation, the wound surface, the affected body part, the origin of the injury and gender. There were no reported adverse effects or problems with tolerability such as local skin irritations. The results justify application of the Symphytum herb extract cream in children with blunt traumata with or without abrasions.

Source: Barna M, Kucera A, Hladkova M, Kucera M. Randomized double-blind study: wound- healing effects of a Symphytum herb extract cream (Symphytumuplandicum Nyman) in children. Arzneimittelforschung. 2012 Jun;62(6):285-9.

2. Therapieergebnisse und Anwendungssicherheit von Symphytum-Herba-Extrakt-Crme in der Behandlung von Dekubitus. [Efficacy and safety of topical Symphytum cream in the treatment of pressure ulcers.]

Abstract: [Original article in German] In an open, prospective use study, 161 patients with 198 decubitus ulcers (pressure ulcers, ITT population) in stages II and III were treated with the topical preparation symphytum herb extract cream. The bandages with the cream were changed every 2–3 days. The primary parameters evaluated were the area of the sore and the depth of the wound (planimetrically in mm). In all, 151 patients with a total of 184 pressure sores (PP population) were included and received treatment over a period of 4 weeks in order to evaluate the treatment results. Complete healing of the pressure sores within 4 weeks was observed in 85.9 % (PP population)/79.8 % (ITT population) of the treated ulcers. Over a treatment duration of 25–30 days, a 89.2 % reduction of the total decubitus area was observed. The same result was found for the depth of the pressure ulcer with a reduction of 88 %. The overall treatment success was from both the perspective of the physician and the patient considered successful in 90.4 %

(5-point scale) of cases and 87.9% (100 mm VAS, PP population). Two cases of local irritation were observed after 25/30 days (1.2 % of the patients with exposure), thus showing very good skin compatibility. The efficacy of symphytum herb extract cream is surprisingly good in the treatment of pressure ulcers.

Source: Stepan J, Ehrlichova J, Hladikova M. Therapieergebnisse und Anwendungssicherheit von Symphytum-Herba-Extrakt-Crme in der Behandlung von Dekubitus. Zeitschrift fur Gerontologie und Geriatrie. 2014;47(3):228-235.

3. Beinwell-Herba-Extrakt-Crme zur Schmerzlinderung bei training induziertem Muskelkater – eine randomisierte, placebokontrollierte Studie. [Topical comfrey cream for the pain relief of exercise-induced muscle soreness - a randomized, placebo- controlled study.]

Abstract: [Original article in German] Topical comfrey preparations are authorized for the treatment of blunt traumas. Effects against muscle pains caused by overload have also been observed. The aim of this explorative, randomized and placebo-controlled pilot study was the preparation of a confirmatory clinical trial in subjects suffering from muscle soreness through the examination of acute pain-relieving effects of a preparation containing a concentrate of the aerial parts of medicinal comfrey (Symphytum uplandicum NYMAN) as an active constituent.

Method: Symptoms of muscle soreness were induced in 24 healthy subjects by a standardised muscle overload of both upper arms under controlled conditions. All subjects were randomised to a single application of verum on one upper arm, and of placebo on the other arm. Pain relieving effects of the study preparation were assessed by the repeated algometric measurement of pain on pressure over the time of 240 minutes. Pain on movement was assessed with the aid of a visual analogue scale. Furthermore, the painless movability of the joint was evaluated.

Results: Due to carry-over effects the intra-individual right arm/left arm comparisons of verum and placebo were unsuitable for an evaluation. In contrast, the alternative evaluation by using the parallel group approach (related to the arm randomised to either the study medication or placebo) showed distinct trends and statistically significant parameters in favour of verum, despite the small group size and the single application of the study preparations. In the evaluation of the responder rate a significant effect was observed for pain on pressure already after 30 and 120 minutes (27.5 vs. 0 % after 30 minutes; p=0.093; 72.7 vs. 25.0 % after 120 minutes; p=0.039).

An improvement of pain on movement was already shown in the comparison of groups after 15 minutes in 66.7 versus 16.7 % of subjects (p=0.036). Assessments of strength of effect led to the demonstration of a trend towards a superiority of verum over placebo after 30 minutes, with statistical significance reached after 120 minutes (39.0 21.2 vs 19.6 22.8% improvement, p=0.060).

Conclusions: The quick onset of pain-relieving effects of the topical comfrey herb extract cream already known from other studies could also be observed when applied against muscle pain related to overload induced muscle soreness. Useful suggestions for the planning of a confirmatory follow-up trial could be derived from this study.

Source: Uebelhack R, Shaudt M, Schmidt M. Beinwell-Herba-Extrakt-Crme our Schmerzlinderung bei traininginduziertem Muskelkater – eine randomisierte placebokontrollierte Studie. J Pharmakol Therap. 2014;23(1):3.

4. Topical comfrey extract: study confirms rapid effects on myalgia due to strain or acute blunt trauma.

Background: The efficacy and tolerability of a topical preparation with an active substance concentrate made from the aerial parts of medicinal comfrey (Symphytum x uplandicum NYMAN) was tested in 215 patients with acute or chronic myalgia of the upper and lower back (active substance n=104, reference n=111) (Kucera et al. 2005). A low dose but otherwise identical preparation (1% versus 10% active substance) was used as a reference. The result was a significantly better and clinically relevant reduction in pain at rest and on movement after 4-5 days with the high active substance concentration. Method: A subgroup analysis was used to examine whether under topical comfrey therapy there are differences in response in myalgia of various origins. A differentiation was made based on pain due to chronic muscle strain (n=135; of which n=56 had active substance) and myalgia due to acute blunt trauma (n=75; of which n=47 had active substance). Five patients with pain of another origin were not included in the analysis. As in the main study, the primary parameter for demonstrating efficacy was a reduction in pain on movement on day 4-5 after commencement of the study, as measured by visual analogue scale. Results: In myalgia of the upper and lower back due to chronic strain as well as

due to acute blunt trauma a statistically highly significant benefit from active substance was seen on day 4-5 as compared to reference (t-test, p = 2 x 10-5 for pain due to chronic strain and p = 1 x 10-5for pain due to blunt trauma) along with a significantly faster onset of the pain relieving effect (Mann-Whitney test, p = 2 x 10-5 for pain due to chronic strain and p = 4 x 10-3 for pain due to acute blunt trauma). The superiority of active substance compared to reference was clinically relevant in both subgroups. Conclusions: Topical comfrey extract has a fast acting analgesic effect in myalgia of the back caused by chronic strain as well as acute blunt injury.

Source: Studie besttigt rasche Wirksamkeit bei Myalgien durch berlastung oder akute stumpfe Traumen. [Topical comfrey extract: study confirms rapid effects on myalgia due to strain or acute blunt trauma.] Kucera M, Hladfkova, M. J Pharmakol Therap. 2012;21(4):112-117.

5. Symphytum: Effizienz auch bei Kindern belegt. [Symphytum: proven efficacy in children].

Abstract: Topical application of comfrey to treat blunt trauma has long been proven in clinical practice. The clinically efficacy of a special ointment preparation of comfrey is backed by appropriate studies, and has now been tested in a new, non-interventional study in children with blunt trauma. The results found a highly significant decrease in severity of the symptoms. [Continuation of research published as Grnwald, J., Bitterlich, N., Nauert, C., Schmidt, M. Z Phytother. 2010;31:61–65.]

Source: Schmidt M. Symphytum: effizienz auch bei Kindern belegt. Naturamed. 2011:36-39. [German]

6. Application and safety of comfrey cream (Symphyti herba) in paediatric treatment of acute blunt traumata (Anwendung und Vertrglichkeit von Beinwellcreme (Symphyti herba) bei Kindern mit akuten stumpfen Traumen).

Abstract: In an open observational study the therapeutic applicability and safety of application of a topical cream preparation from the aerial plant parts of the comfrey cultivar “Symphytum uplandicum Nyman ‘Harras’” was tested in 196 children in the age of 4 to 12 years with respect to the paediatric treatment of acute blunt traumata (contusions, strains and distortions). The extent of symptom improvement observed in this study (pain on palpitation, pain in motion, functional impairment, oedema and haematoma) was found in the range of 84.5 to 100% for the single parameters (p < 0.001) with at the same time an excellent tolerability and compliance.

Topical comfrey cream was therefore confirmed as a remedy of choice for the treatment of acute blunt traumata in children.

Source: Grnwald, J., Bitterlich, N., Nauert, C., Schmidt, M. Application and safety of comfrey cream (Symphyti herba) in paediatric treatment of acute blunt traumata (Anwendung und Vertrglichkeit von Beinwellcreme (Symphyti herba) bei Kindern mit akuten stumpfen Traumen)

. Anwendung und Vertrglichkeit von Beinwellcreme (Symphyti herba) bei Kindern mit akuten stumpfen Traumen. Z Phytother. 2010;31:61–65. [German]

7. Final report of the monitoring of the rehabilitation in cervical spine functional disorders in medication coverage with the help of Traumaplant.

Abstract: the authors present a comparative study that was carried out in cooperation with the two above-mentioned rehabilitation centers. It involves therapeutic experiences with functional disorders of the cervical vertebral column – one of the most common illnesses for which patients come into outpatient rehabilitation and the health spas. Materials and Methodology: since patients who come for outpatient rehabilitation show other characteristics than patients in health spas, the authors decided to carry out the study at two locations. Fifty patients in outpatient care were included in the project, and 300 patients staying as inpatients in the health spa – 255 patients completed the study. Therapeutic results obtained in the Revitalis rehabilitation center and the Bojnice health spa are presented. Results: Rehabilitation with the aid of pharmacotherapeutic support using the ointment Traumaplant proved to be significantly or numerically more effective with regard to the relaxation of contracted muscles and improvement of the mobility of the fasciae.

Source: Guth A. Final report of the monitoring of the rehabilitation in cervical spine functional disorders in medication coverage with the help of Traumaplant. Lek Obz. 2009;58(suppl):1-5. [German]

8. Wound healing effects of a Symphytum herb extract cream (Symphytum x uplandicum NYMAN): results of a randomized, controlled double-blind study.

Abstract: Wound healing effects of a topically applied preparation (Traumaplant) containing a concentrate (10 % active ingredient) from the aerial parts of medicinal comfrey (Symphytum x uplandicum NYMAN) were examined in a randomized clinical double-blind study including 278 patients with fresh abrasions (verum: n = 137), among them 64 patients of up to 20 years of age (verum n = 29, reference product n = 35). An otherwise identical low-dose preparation (1 % active ingredient; n = 141) was used as a reference. RESULTS: After 2-3 days of application of the study medication a highly significantly and clinically relevantly faster initial reduction of wound size of 49 + or - 19 % versus 29 + or - 13 % per day in favour of verum (p < 5x10(-21)) was found. From linear regression time to complete healing was determined to be 2.97 days faster with verum than with reference (4.08 vs. 7.05 days, p = 7.4 x 10(-45) in the t-Test comparison of regression lines). The physicians rated efficacy as good to very good in 93.4 % of cases, as compared to 61.7 % in the group treated with the reference product (p = 2 x 10(-11)).

On a scale of 0-100 verum was rated with 84.4 + or - 10.1 points by the patients themselves. The reference product was rated with 65.5 + or - 24.8 points (p = 6.1 x 10(-18)). In subgroup analyses no significant influence of abrasion area, gender and age on healing effects was found, albeit a tendency towards better effects with increasing age was observed. No adverse effects or problems with drug tolerability occurred. Specifically, cutaneous reactions were observed in none of the patients throughout the 10 day observation phase. CONCLUSIONS: Symphytum herb extract can be attributed distinct wound healing effects, effects that can explicitly be used in paediatry.

Source: Barna M, Kucera A, Hladcova M, Kucera M. Wound healing effects of a Symphytum herb extract cream (Symphytum x uplandicum NYMAN: ): results of a randomized, controlled double-blind study. Wien Med Wochenschr. 2007;157(21-22):569-74. [German]

9. Topical Symphytum herb concentrate cream against myalgia: a randomized controlled double-blind clinical study.

Abstract: The effectiveness and tolerability of the topical Symphytum product Traumaplant (Harras Pharma Curarina, Mnchen, Germany) (10% active ingredient of a 2.5:1 aqueous- ethanolic pressed concentrate of freshly harvested, cultivated comfrey herb [Symphytum uplandicum Nyman], corresponding to 25 g of fresh herb per 100 g of cream) in the treatment of patients with myalgia (n=104) were tested against a 1% reference product (corresponding to 2.5 g of fresh comfrey herb in 100 g of cream; n=111). The primary efficacy parameter in this double-blind, reference- controlled, randomized, multicenter study of 215 patients with pain in the lower and upper back was pain in motion, assessed with the aid of a visual analogue scale.

Secondary efficacy parameters included pain at rest, pain on palpation, and functional impairment. With high concentrations of the treatment product, amelioration of pain on active motion (P<5 x 10 -9), pain at rest (P<.001), and pain on palpation (P=5 x 10 -5) was significantly more pronounced than that attained with the reference product and was clinically highly relevant. A number needed to treat of 3.2 was calculated from the study results. Global efficacy was significantly better (P=1 x 10 -8) and onset of effects was faster (P=4 x 10 -7) with the high- concentration product. Tolerability of the highly concentrated study product was good to

excellent in all patients. Study results confirm the known anti-inflammatory and analgesic effects of topical Symphytum cream. As a new finding, applicability in certain forms of back pain can be concluded.

Source: Kucera M, Barna M, Horcek O, Klal J, Kucera A, Hladkova M. Topical Symphytum herb concentrate cream against myalgia: a randomized controlled double-blind clinical study. Adv Ther. 2005 Nov-Dec;22(6):681-92.

10. Efficacy and safety of topically applied Symphytum herb extract cream in the treatment of ankle distortion: results of a randomized controlled clinical double blind study.

Abstract: In a controlled, double blind, randomized multicentre study, the efficacy and safety of the topical comfrey product Traumaplant (10% active ingredient of a 2.5:1 aqueous ethanolic pressed juice of freshly harvested, cultivated comfrey herb (Symphytum x uplandicum NYMAN), corresponding to 25 g of fresh herb per 100 g of cream; n = 104) was tested against a 1% product (corresponding to 2.5 g of fresh comfrey herb in 100 g of cream; n = 99) in 203 patients with acute ankle distortion. With the high concentration, decrease of the scores for pain on active motion, pain at rest and functional impairment was highly significant and clinically relevant on days T3-4 as well as T7 (p < 0.001). Amelioration of swellings as compared to reference was also significant on day 3-4 (p < 0.01). Efficacy was judged good to excellent in 85.6% of cases with verum and in 65.7% of cases with reference on day 3-4. Overall tolerability was excellent.

Source: Kucera M, Barna M, Horcek O, Kovrikov J, Kucera A. Efficacy and safety of topically applied Symphytum herb extract cream in the treatment of ankle distortion: results of a randomized controlled clinical double blind study. Wien Med Wochenschr. 2004 Nov;154(21- 22):498-507.

11. Effects of Symphytum ointment on muscular symptoms and functional locomotor disturbances.

Abstract: In an open, uncontrolled study, 105 patients with locomotor system symptoms were treated twice daily with an ointment containing a Symphytum active substance complex. A clear therapeutic effect was noted on chronic and subacute symptoms that were accompanied mainly by functional disturbances and pain in the musculature. The preparation was most effective against muscle pain, swelling and overstrain, arthralgia/distortions, enthesopathy, and vertebral syndrome. Activity was weaker against degenerative conditions, for which the ointment may have an adjuvant role with the aim of improving muscular dysfunction and alleviating pain.

Source: Kucera M, Kalal J, Polesna Z. Effects of Symphytum ointment on muscular symptoms and functional locomotor disturbances. Adv Therapy. 2000;17(4):204-210.

12. The local treatment of acute supraspinatus tendon syndrome with a Symphytum active substance complex ointment.

Abstract: In a comparative study on patients suffering from acute supraspinatus tendon syndrome, the efficiency of a plant active substance complex was tested within the context of a conservative treatment in which the preparation was combined, as a percutaneous adjuvant treatment, with local infiltration therapy. The clinical criteria of “day pain”, “night pain”, and the abduction-provoked “painful arc” were used as assessment criteria. During the three-week study time period, the pain symptoms and the correlated functional disturbances decreased considerably more rapidly with local application of the Symphytum active substance complex than in the control group without the additional percutaneous treatment. The differences between the corresponding assessment criteria proved to be statistically significant.

Source: Mayer G. The local treatment of acute supraspinatus tendon syndrome with a Symphytum active substance complex ointment. Dtsch Z Sportmed [German J Sports Med]. 1993;44(3):121-124.

13. The local treatment of contusions and distortions of the knee joint with a Symphytum active substance complex ointment.

Abstract: The local efficacy of a phyto-antitraumatic (an ointment containing a Symphytum active substance complex) was investigated in 22 patients with acute contusions and distortions of the knee joint. During the course of treatment, the clinical symptoms (joint swelling, pain on active and passive movement, local rest pain) decreased rapidly and soon had completely subsided. All patients were completely free of pain after 10 to 14 days or even earlier. The tolerance of the Symphytum ointment was good. No systemic or allergic reactions were observed.

Source: Mayer G. The local treatment of contusions and distortions of the knee joint with a Symphytum active substance complex ointment. Orthopedic Clinic of the Medical Department of Ernst-Moritz-Arndt University of Greifswald. Original Article. 1992.

14. Effect of a Symphytum ointment with sports injuries of the knee joint.

Abstract: Treatment with a Symphytum peregrinum (synonymous with Symphytum x uplandicum NYMAN) ointment was carried out for an average of 8 days on 40 patients suffering from recent knee joint injuries, distortions, and contusions which did not require surgery. Except for physical measures such as compression bandages, ice packs, and directions for independent exercise therapy, no other additional treatment was carried out. Assessment criteria were pain, swelling, and restriction of movement. Of the patients, 34 (85%) rated the efficacy of the preparation as good to very good, and only 9 (15%) rated the therapeutic result as less satisfactory. All 40 patients assessed the tolerance of the ointment positively. No side effects occurred in any of the cases. It can be concluded from the results that the 10% Symphytum ointment is very suitable for the local treatment of knee joint injuries.

Source: Hess H. Effect of a Symphytum ointment with sports injuries of the knee joint. Dtsch Z Sportmed [German J Sports Med]. 1991;42(4):156-162.

15. The local treatment of acute lateral distortions of the ankle joint with an ointment containing a Symphytum active substance complex.

Abstract: In a comparative study, the efficacy of an ointment containing a Symphytum active substance complex was tested with acute distortions of the ankle join in comparison to conventional cutaneous cryotherapy. The clinical criteria of resting pain pain on movement, and swelling in the region of the injured joint were used as assessment parameters. During the 14-day treatment period, the pain symptoms and post-traumatic swelling improved more rapidly with local application of the Symphytum ointment than with the control treatment. The differences between the assessment parameters for the two forms of topical treatment were statistically significant.

Source: Mayer G. The local treatment of acute lateral distortions of the ankle joint with an ointment containing a Symphytum active substance complex. Acta Therapeutica. 1991;17:89- 100.

Effect of an active substance complex from Symphytum on epithelialization. Abstract: The wound-healing efficacy of a 10% Symphytum peregrinum (synonymous with

Symphytum x uplandicum NYMAN) ointment was tested on experimentally produced open shallow wounds with an intact columnar layer in healthy volunteers. The ointment base and a polyacrylamide agar gel without active substances served as controls. After application of the Symphytum peregrinum ointment, the time taken for the wounds to heal completely was clearly reduced in comparison to the two control preparations, and the difference with respect to the active substance-free ointment vehicle was statistically significant (p < 0.05).

Source: Niedner R. Effect of an active substance complex from Symphytum on epithelialization.

Acta Therapeutica. 1989;15:289-297.

ADDITIONAL SCIENTIFIC PUBLICATIONS

Comfrey Herbal Extract in Phytotherapy (Beinwell-Herbaextrakt in der Phytotherapie).

Abstract: [Original article in German] A specifically selected comfrey herb extract for phytotherapy Comfrey (Symphytum officinale sensu lato) is an outstanding example for the rational use of medicinal plants against blunt traumas such as contusions, strains and sprains. The use against muscle and joint complaints, e.g. against muscle pain in the back, is newly added to these well-established indications. A high performance cultivar was specifically selected and cultivated for the use in medicinal products. It was registered at the European Plant Variety Office with the denomination Symphytum uplandicum Nyman >Harras<. In an exemplary way this variety fulfils the requirements for quality, efficacy and safety. Among other factors, quality is given by the reproducible cultivation, the - within narrow margins - constant phytochemical composition and the non-application of herbicides and pesticides. The efficacy against blunt traumas with and without abrasions has been demonstrated in clinical trials. It also

includes the application in children. Safety is concluded from the observation of an exceptionally good clinical tolerability and from the lack of potentially toxic pyrrolizidine alkaloids in the harvested plant material. From the point of view of phytotherapy the fact that all clinical trials with the preparation from the aboveground plant parts have been performed with exactly the same plant variety and quality is also unique: It allows a direct transferability between studies of clinical findings with respect to efficacy and safety.

Source: Schmidt M. Beinwell-Herbaextrakt in der Phytotherapie. Zeitschrift fur Phytotherapie. 2012;33(3):114-117.

18. Comfrey ointment- a topical analgesic (Beinwell-Salbe – ein topisches Analgetikum).

No abstract available.

Source: Guth A., Schmidt M. (HWS-Syndrom. Beinwell-Salbe – ein topisches Analgetikum) [Comfrey ointment – a topical analgesic]. Naturamed. 2010;25(3):26-28. [German]

19. Comfrey cream surpasses pure physical therapy (Beinwellcreme bertrifft rein physikalische Therapie).

No abstract available.

Source: Guth A., Schmidt M. Beinwellcreme bertrifft rein physikalische Therapie [Comfrey cream surpasses pure physical therapy]. Der Allgemeinarzt. 2010; 32(7):46. [German]

20. Comfrey cream increases the success of physical therapy (Beinwellcreme steigert den Erfolg der physikalischen Therapie).

No abstract available.

Source: Guth A. Beinwellcreme steigert den Erfolg der physikalischen Therapie [Comfrey cream increases the success of physical therapy]. Allgemeinarzt. 2010;32(Supple 8):2-4.

Tolerability of Traumaplant cream in young patients (4-12 years) with intact skin (TRACY-1). Harras Pharma. 2011. Data unpublished.

No abstract available.

Tolerability of Traumaplant cream in young patients (4-12 years) with non-intact skin (TRACY-2). Harras Pharma. 2011. Data unpublished.

No abstract available.

NON-CLINICAL RESEARCH

Topic: High-performance cultivar ‘Harras’ as a contribution to quality, efficacy and safety of comfrey (Symphytum x uplandicum Nyman).

Abstract: The cultivation of a high performance cultivar especially selected for the absence of pyrrolizidine alkaloids may therefore be considered an important contribution to efficacy and safety of comfrey preparations. Based on selection, the cultivar ‘Harras’ (Symphytum uplandicum Nyman) was introduced into cultivation. The cultivar excels in the absence of detectable quantities of pyrrolizidine alkaloids in the aerial plant organs.

Source: Schmidt M. Topic: High-performance cultivar ‘Harras’ as a contribution to quality, efficacy and safety of comfrey (Symphytum x uplandicum Nyman). [Thema: High-performance cultivar ‘Harras’ as a contribution to quality, efficacy and safety of comfrey (Symphytum x uplandicum Nyman]

Z Arznei-Gewurzpfla. 2008;13(4):182-183. [German].

Published Studies on Hintonia latiflora

1.Hintonia concentrate – for the dietary treatment of increased blood sugar values: results of a multicentric, prospective, non-interventional study with a defined dry concentrate of hintonia latiflora. [Translated from German] Preparations from the bark of hintonia latiflora are used to regulate the blood sugar levels. The objective of this study was to prove the nutritional benefit within the framework of a dietary treatment of increased blood sugar values with pre-diabetes and slight diabetes type 2 as well as the assessment of the tolerance and application safety. In an open, prospective, multicentric and non-interventional application study, the effects of a dry concentrate from the bark of hintonia latiflora in the form of capsules were examined for the laboratory parameters of the blood sugar levels (HbA1c, fasting and postprandial glucose) as well as for the development of diabetic accompanying symptoms (sweating, gastrointestinal symptoms, paraesthesiae, itching and neuropathies). Particular attention was also given to the tolerance and (if available) further clinical (laboratory) parameters (blood pressure, liver values and blood lipids). An eight-month treatment was documented in 178 test persons with type 2 diabetes / pre-diabetes, who were treated with oral antidiabetics and / or insulin or only with a diet. At the end of the study, 177 data records were available. The HbA1cvalues improved over the course of the study with a high level of clinical relevance and significance from 7.2 0.4% to 6.4 0.5%, in accordance with a relative improvement by 10.4% (p < 0.0001). In parallel, the values of fasting and postprandial glucose also improved by an average of 23.3 12.5% (from 152.1 27.4 mmol/l to 114.4 18.2 mmol/l) and 24.9 11.4% (from 189.5 34.1 mmol/l to 140.1 22.3 mmol/l). The sum score of the diabetic accompanying symptoms improved from initially 4.8 points to 1.3 points at the end of the study. Improvements were also determined in blood pressure, blood fats and liver values. The tolerance was excellent, no unwanted effects occurred, in particular no hypoglycaemic episodes. In 55 of 114 patients with antidiabetic medication (39.5%), the substance could be reduced (n = 45) or stopped entirely (n = 10). The study confirms the positive effects of the dry concentrate from the bark of hintonia latiflora on the main parameters of the blood sugar levels and the diabetic accompanying symptoms. In the event of pre-diabetes or minor cases of type 2 diabetes mellitus, this can contribute towards stabilizing the blood sugar homeostasis in particular, achieving a lower load from accompanying medication and deferring the necessity of using oral antidiabetic drugs and

/ or insulin. [Schmidt M, Hladikova M. Hintonia concentrate – for the dietary treatment of increased blood sugar values: Results of a multicentric, prospective, non-interventional study with a defined dry concentrate of hintonia latifloa. Naturheilpraxis mit Naturmedizin. February 2014.]

2.Treatment of mild and moderate type-2 diabetes: open prospective trial with Hintonia latiflora extract. Background: Extracts from the bark of Hintonia latiflora are used as dietetic measures to support the regulation of glucose metabolism and the stabilization of blood glucose values. Methods: A dry concentrated extract from the bark of Hintonia latiflora in capsule form was tested in an open, prospective clinical study in 41 dietetically stabilized subjects with type 2 diabetes. The effects on parameters of blood glucose control were documented over a period of six months. Results: Fasting and postprandial glucose and the HbA1c value declined significantly. In the case of HbA1c, this meant a reduction of the absolute value from 7.49 0.72% to 6.82 0.67% (from 58.4 to

51.0 mmol/mol Hb; intention to treat (ITT) population). Furthermore, cholesterol and triglycerides were slightly reduced and no negative effect on other laboratory parameters and no change of the liver values were observed. Tolerance was very good. In particular, no side effects and no hypoglycemic episodes or worsening of diabetic symptoms occurred. Conclusions: The study confirms the positive effect of extracts from the bark of Hintonia latiflora on blood glucose values suggesting a potential benefit in the management of glucose metabolism in cases of type 2 diabetes.[Korecova M, Hladikova M. Treatment of mild and moderate type-2 diabetes: open prospective trial with Hintonia latiflora extract. European Journal of Medical Research. 2014;19(1):16.]

3.Hintonia latiflora in patients with type 2 diabetes: A long-term study. [Hintonia latiflora bei Typ-2- Diabetes.] The antidiabetic efficacy and safety of an extract from Hintonia latiflora (drug-extract ratio 1:4.5, extraction solvent 32% ethanol) was tested in a monocenter open, uncontrolled study on 30 patients with type 2 diabetes. Patients were adjusted to a stable diet at least two months prior to therapy and during the entire duration of the study in order to rule out a dietary impact on the study outcome. After 12 months of treatment, fasting blood glucose was reduced by 20.6%, postprandial glucose by 19% and the mean HbA1c by 10.3% (p < 0.001). In the patients remaining in the study, these parameters were stable thereafter (up to 33 months of treatment). There were no hypoglycemic episodes or adverse events throughout the entire treatment period. [Korecova M, Hladicova M, Korec R. Hintonia latiflora bei Typ-2-Diabetes. Zeitschrift fr Phytotherapie. 2006;27:272-278.]

4.Natural treatment of Type II diabetes utilizing an herbal antidiabetic product. Case Report. [Naturheilkundliche Therapie des Typ-II-Diabetes mit Hilfe des Phyto-Antidiabetikums.] One female patient with diabetes mellitus received an 8-week course with 5x50 Hintonia drops daily. Fasting glucose decreased in a female patient after a three-week treatment with Hintonia after a prior exacerbation of glycaemic control, despite the use of metformin as an oral antidiabetic. She was initially considered for insulin treatment. During her 8-week course with 5x50 Hintonia drops daily, the fasting glucose level was reduced from 191 mg to 176 mg. No adverse reactions were observed. [Ploss O. Naturheilkundliche Therapie des Typ-II-Diabetes mit Hilfe des Phyto- Antidiabetikums. HP Naturheilkunde. 2002;25(1/2):40-44.

5.Therapeutic trial with Copalchi [Hintonia latiflora] bark in patients with impaired glucose tolerance. [Therapieversuch mit Copalchi-Rinde bei pathologischer Glucosetoleranz.] The effect of 2 - 3x30 Hintonia drops on glucose tolerance was examined on a group of fourteen subjects with impaired glucose tolerance not treated with oral antidiabetics or insulin. Although an effect of an 8- week onwards intake of the investigational medicinal product exhibited no immediate effect on the glucose tolerance test, positive long-term effects were seen in at least 7 patients (treated for several years) because none of these cases developed full diabetes. Diabetes is a progressive disease and the necessity for the adjustment to antidiabetic drugs is merely a matter of time. The delaying of the time point of an antidiabetic therapy may be considered to be an important prophylactic factor. No

adverse reactions were recorded and reported [Machens R. Therapieversuch mit Copalchi-Rinde bei pathologischer Glucosetoleranz. Erfahrungsheilkunde. 1996;45(9):605-608.]

6.A long-term test with Copalchi fluid extract , a herbal anti-diabetic drug. [Eim Langzeitversuch mit Copalchi-Fluidextrakt, einem pflanzlichen Antidiabetikum.] Open long-term study. Fourteen patients with type 2 diabetes received approximately 10 drops of a copalchi (Hintonia latiflora) extract twice daily for a duration of 10 months. The patients were stabilized to glibenclamide and diet prior to the administration of copalchi drops. In 9 patients “good” to “very good” improvement of their HbA1c –values was found and in 4 of these patients glibenclamide could be discontinued within 10 months. With regard to safety, no pathologic changes in liver parameters during long-term application of copalchi drops in 16 subjects with diabetes mellitus were detected. [Machens R. Eim Langzeitversuch mit Copal chi-Fluidextrakt, einem pflanzlichen Antidiabetikum. Erfahrungsheilkunde. 1992;6:416-420.]

7.Two cases of spontaneous regression of diabetes mellitus Type 2 after treatment with a phytotherapeutic natural medicine. [Zwei Flle spontaner Regression des Diabetes mellitus Type 2 nach Behandlung mit einem Phytotherapeutikum.] The effects of copalchi drops (Hintonia latiflora) were assessed in eight patients with diabetes mellitus. An initial increase of HbA1c values on short- term intake of 20 drops 3 times daily for 4 weeks was found. A substantial decrease in the fasting glucose level was observed in 4 of the 8 cases, whereas HbA1c -values were unaltered or increased in 7/8 patients. With regard to the relatively long half-life of HbA1c it was concluded that a measurement after only 4 weeks of copalchi intake is not likely a meaningful result. No adverse reactions were observed. [Machens R. Zwei Flle spontaner Regression des Diabetes mellitus Type 2 nach Behandlung mit einem Phytotherapeutikum. Erfahrungsheilkunde. 1991;6:433-436.]

8.Oral diabetes therapy with a copalchi extract. [Orale Diabetestherapie mit einem Eupharbiazeenextrakt.] In order to determine the effects of a liquid copalchi (Hintonia latiflora) extract, a dose of 50 drops three times daily was evaluated in healthy volunteers and diabetic patients. The investigation was performed by the use of a cross-over design on three consecutive days. Baseline glucose levels were measured in 10 healthy volunteers, in 15 patients with mild forms of diabetes mellitus, especially in those suffering type 2 diabetes, in cases of moderately severe diabetes mellitus (as judged by a daily insulin requirement of 30-40 IU), and in severe and insulin- resistant cases of diabetes type 2 and in diabetes type 1 (n=6). Results: In the ten healthy volunteers the administration of insulin (5 IU) distinctly lowered blood glucose levels, whereas the application of the copalchi extract (50 drops) did not produce hypoglycaemia. In the fifteen patients with mild forms of diabetes mellitus (especially in type 2 diabetes) the effects were expressed in a reduced requirement of auxiliary insulin from 15-25 IU to 5-10 IU. Insulin was discontinued in cases where the administered dose was in the range of 10-15 IU. Two reports were presented in which up to 25 IU of insulin were replaced by copalchi 50 drops/ 3 times daily with even better effects on glucose control. In cases with moderately severe diabetes mellitus (as judged by a daily insulin requirement of 30-40 IU) the insulin sparing effect was less, reaching only 5 IU insulin reduction at its maximum. A reduction in renal urine excretion was also detected. The observed effects were dose-dependent:

two patients who accidentally reduced the ingested dose to 20 drops t.i.d. experienced a reoccurrence of diabetic symptoms such as thirst, diuresis and an increase of blood glucose within 1- 2 days. In both cases the resetting of the dose to the initially recommended quantity of 50 drops

t.i.d completely restored these effects. In severe and insulin-resistant cases of diabetes type 2 and in diabetes type 1 (n=6) the blood glucose-lowering effect was far less pronounced or missing, as demonstrated in two case reports. Co-symptoms of diabetes such as pruritus or thirst were effectively counteracted by the intake of the investigational extract. Adverse reactions were not recorded in any of the 31 cases. [Kuhr R. Orale diabetestherapie mit einem Eupharbiazeenextrakt. Landarzt. 1953;29(23):542-549.]

9.Clinical validation for an herbal Hintonia product. [Klinisches Gutachten ber das Hintonia latifloria Produkt.] The study was undertaken to compare the influence of Hintonia drops on blood glucose level, urinary glucose and acidosis, in mild to moderate cases of diabetes, especially in patients suffering type 2 diabetes. The dosages applied to patients with mild to moderate diabetes, (especially patients suffering type 2 diabetes) ranged between 3 x 30-50 drops/day. In order to avoid an influence of the diet, only patients were tested who were compliantly adjusted to a standard diet for a minimum of 4-5 days. In five of eight cases a distinct improvement in symptoms was observed. No adverse reactions were observed in any of the described cases. [Pellegrini A. Klinisches Gutachten ber das Hintonia latiflora Produkt. Sonderdruck Fa. Sippel, Konstanz. 1951:1-7.]

10.Clinical case reports: the effectiveness of the oral antidiabetic Hintonia latiflora. [Bericht ber die Behandlung mit dem peroralen Antidiabetikum Hintonia latiflora.] Severe cases did not satisfactorily respond to this treatment, whereas in mild to moderate cases a significant reduction of diabetic symptoms was achieved, as expressed in a distinct reduction of urinary glucose and of blood glucose. Co-morbidity caused by the diabetes, such as pruritus, nightly sweating, furunculosis and thirst resolved quickly. Even in cases of severe diabetes (in whom no noticeable reductions of blood glucose values were observed), complaints - related to early stages of acidosis such as headache, tiredness or dizziness - were reduced. No adverse effects were observed. The author concluded that especially mild and moderate cases or diabetes and type-2 diabetes can successfully be treated with Hintonia drops. In severe cases of juvenile diabetes the treatment can at least positively influence the general health condition of the patient, even though no amelioration of blood sugar values would be expected. [Schmid P. Bericht ber die Behandlung mit dem peroralen Antidiabetikum Hintonia latiflora. Sonderdruck Fa. Sippel, Konstanz. 1951: 1-4.

11.Review of the oral antidiabetic, Hintonia latiflora. [Erfahrungsbericht mit dem peroralen Antidiabetikum Hintonia latiflora.] Following a run-in period of at least 6 days with a standardized diet, a 6-day treatment phase with Hintonia, 30-50 drops 3-times daily was started. Thereafter, the drops were discontinued and during this post-treatment observation period insulin was replaced as needed. “Severe” cases of DM were defined as states with an acidosis and a regular excretion of >50 g of glucose with the urine. “Moderately severe” cases were defined as having no acidosis and 20-50 g of glucose in the urine, whereas “mild” cases exhibited a daily urinary excretion below 20 g glucose. None of the patients with severe diabetes responded to the treatment with Hintonia drops.

In contrast, a reduction of blood sugar and glucose excretion into the urine was achieved in 9/14 patients with moderate diabetes. The effect could be maintained over the whole treatment period and lasted up to 2-3 days after discontinuation. With the exception of diarrhea in one case during the treatment period (6 days), no adverse reactions were observed. [Vida F. Erfahrungsbericht mit dem peroralen Antidiabetikum Hintonia latiflora. Med Welt. 1951;20:1623-1624.]

12.Contribution to diabetes treatment. [Beitrag zur Diabetes-Behandlung.] Diabetic patients were treated with Hintonia drops (average dose: 3x30 drops/day) within a period of 4 months. The author reported that mild to moderate cases responded best to the treatment. In patients previously (and unsuccessfully) treated with diet only diabetic symptoms reverted to normal within only 14 days of treatment with Hintonia drops. Glycaemia, glucosuria and the amount of urine within 24 hours were distinctly reduced. Accompanying diabetic-related diseases and damages such as furunculosis or pruritus were completely resolved, whereas the late occurring diabetic damages such as polyneuritis or retinopathy were not influenced. The author also noted that patients immediately felt a subjective amelioration of symptoms, as expressed in an amelioration of weakness, tiredness or nervous restlessness. No adverse effects were observed. [Ritzmann H. Beitrag zur Diabetes- Behandlung. Hippokrates. 1950;21(6):161-168.]

13.Experimental Animal Studies on the Hypoglycemic Effects of a Copalchi Extract. [Tierexperimentelle Untersuchungen zur hypoglykamischen Wirksamkeit eines Copalchi- Extraktes.] The hypoglycemic effects of a Copalchi extract was tested in 60 adults – male and female

– Wistar rats in the presenta randomized, placebo-controlled, parallel-comparative animal study. A control group receiving only an Altromin standard chow was compared to treatment groups which received an Altromin chow enriched with Copalchi dry substance at 0.028% m/m or at 0.28% m/m. The study period was 30 days. The distinctly significant blood glucose lowering effect of the Copalchi extract could be demonstrated in both treatment groups. No significant difference in the antidiabetic effect was seen between the two concentrations. The onset of action of the Copalchi extract was observed between treatment days 1 and 3. A 20-25% decrease in the blood glucose concentration was achieved between the 7th and 15th day of treatment and remained at this level thereafter. This plateau was reached in the female rats already between treatment day 3 and 5. The parallel observed increase in the mean body weight was not striking and generally was the same between the test animals and the control animals. [Pinto A, Capasso A, Sorrentino L. Tierexperimentelle Untersuchungen zur hypoglykamischen Wirksamkeit eines Copalchi-Extraktes.

Antidiabetika. 1997;47(7):829-833.]

Published Studies on BosPure Boswellia

1. Novel evidence for curcumin and boswellic acid induced chemoprevention through regulation of miR-34a and miR-27a in colorectal cancer. Colorectal cancer (CRC) is one of the most common causes of cancer-associated mortality worldwide, but it is truly a preventable disease. Both curcumin and boswellic acids are well-established dietary botanicals with potent anti-tumorigenic properties which have been shown to modulate multiple oncogenic pathways. Recent data suggest that the chemopreventive effects of these botanicals may in part be mediated through regulation of key cancer-related microRNAs (miRNAs) and their downstream gene targets. Here, we investigated the anti-tumorigenic effects of curcumin and 3 acetyl-11-keto-β- boswellic acid (AKBA) on modulation of specific cancer-related miRNAs in CRC cells and validated their protective effects in vivo using a xenograft mouse model. Both curcumin and AKBA inhibited cellular proliferation, induced apoptosis and cell cycle arrest in CRC cell lines, and these effects were significantly enhanced with combined treatment. Gene-expression arrays revealed that curcumin and AKBA regulated distinct cancer signaling pathways including key cell-cycle regulatory genes. Combined bioinformatics and in-silico analysis identified apoptosis, proliferation and cell-cycle regulatory signaling pathways as key modulators of curcumin and AKBA-induced anti-cancer effects. We discovered that curcumin and AKBA induced upregulation of tumor-suppressive miR-34a and downregulation of miR-27a in CRC cells. Furthermore, we demonstrated in a mouse xenograft model that both curcumin and AKBA treatments suppressed tumor growth, which corresponded with alterations in the expression of miR-34a and miR-27a, consistent with our in vitro findings. Herein we provide novel mechanistic evidence for the chemopreventive effects of curcumin and AKBA through regulation of specific miRNAs in colorectal cancer. [Toden S, Okugawa Y, Buhrmann C, Nattamai D, Anguiano E, Baldwin N, Shakibaei M, Boland CR, Goel A. Cancer Prev Res (Phila). 2015 Feb 23. (Epub ahead of print).]

2. The Effect of Exercise and Nutritional Supplementation on Proinflammatory Cytokine Expression in Young Racehorses During Training. The inflammatory response to vigorous exercise ranges from the mild symptoms of delayed-onset muscle soreness to debilitating injuries affecting soft tissue, joint, and bone. Although there is a great deal of information available on the inflammatory response to exercise in human athletes, less information is available regarding the inflammatory response to exercise in young horses undergoing training for racing careers. Here, we assessed the cytokine response to exercise in a group of young Thoroughbred racehorses during their initial training. Because there is interest in nonpharcacologic approaches to control or ameliorate exercise-induced inflammation, we also examined the anti-inflammatory effect of a nutritional supplement fed to half of the horses undergoing training. Twenty-five Thoroughbred horses aged 2 years were followed through their initial race training. Peripheral blood samples were collected at various times during the exercise for the quantitation of lactic acid, oxidative stress, and inflammatory cytokine gene expression. There was an intensity- dependent effect of exercise on lactate, malondialdehyde, and proinflammatory cytokine gene expression. Although training itself was associated with an overall reduction in inflammatory markers, horses receiving the supplement exhibited further reduction in their indicators of

inflammation. As such, this study provides novel evidence of nutritional supplementation reducing postexercise inflammation. [Horohov D, Sinatra S, Chopra R, Jankowitz S, Betancourt A, Bloomer R. The Effect of Exercise and Nutritional Supplementation on Proinflammatory Cytokine Expression in Young Racehorses During Training. Journal of Equine Veterinary Science (2012) 1-11.]

3. Clinical Evaluation of an Herbal Formulation, Rhulief, in the management of knee osteoarthritis. 54 subjects were screened, 30 got enrolled and 28 completed the study. The demographics and baseline characteristics of the two treatment groups were comparable.

Joint pain is measured by querying the patient and scoring it as no/mild/moderate/severe during each visit. There was significant improvement in pain scores within the groups I and II over a period of 12 weeks, but there was no significant difference between the groups. At baseline 85.71% of the subjects were in moderate/severe category group I and 78.57% in group II. At the end of the study, only 21.43% subjects in group I were in moderate/severe category, whereas 50% in group II were still in the moderate/severe category.

Walking distance refers to the maximum distance a person is able to walk at a stretch without limiting pain and was recorded at each visit. Statistically significant improvement in % individuals scoring walking distance more than 1000 meters was seen within both groups over a period of 12 weeks. In group I, 92.86% of subjects could walk >1000m compared to 85.71% in group II after treatment.

Joint line tenderness was elicited by palpating along the joint line and was measured by querying the patient and recording the response as no/mild/moderate/severe. Significant improvements were seen in both groups. The % of patients in category moderate/severe decreased from 85.71 to 7.14 in group I over a period of 12 weeks, whereas in group II, it came down from 78.57 to

21.43. It showed that 92.85% of the patients in group I had improvement or has no joint line tenderness as compared to 78.57% in group II.

Significant improvement in crepitus and range of movements were seen within both groups. The other parameters studied, namely, joint swelling, warmth of joint, gait and thigh measurements were not affected by any of the drugs. The safety of the test drug was evaluated by measuring vital signs (systolic and diastolic blood pressure, pulse rate, respiratory rate), haemogram (TC, DC, ESR), liver function tests (blood urea, serum creatinine). None of these parameters were adversely modified by Rhulief. [Kizhakkedath R, Antony B, Benny M, Kuruvilla BT. Clinical Evaluation of an Herbal Formulation, Rhulief, in the management of knee osteoarthritis. Osteoarthritis and Cartilage Vol. 19 Supplement 1, Pages S145-S