5/25/2009

Boswellia Serrata AKBA

Nutra Specialities India March 2009

Boswellia Serrata AKBA

Rejuvenates Joint Cartilage by inhibiting the 5-lipoxygenase activity

5/25/2009

What is Boswellia Serrata

Boswellia has long been an Ayurvedic medicine. Boswellia Serrata contains boswellic acids which plays as a vital role for treatment of various anti-inflammatory conditions. Boswellia shows good improvements in curing Inflammation, Colitis, Cancer, Osteoarthritis, Bronchial Asthma, etc. Boswellia extract is considered as an alternative to NSAID due to less side effects.

Historical Boswellia
Boswellic acids are natural extracts of the plant Boswellia serrata which are biologically active pentacyclic triterpenes of Frankincense derived from the gum resin of the tree of the family Burseraceae. Frankincense is being used extensively all over the world in various clinical conditions, specifically employed to alleviate the signs and symptoms in chronic arthritis conditions. Frankincense that had been a compound in the European pharmacopeia till 1900, went into oblivion since then.

5/25/2009

Boswellia Composition
Boswellia consists of 6 Major acids
1. 2. 3. 4. 5. 6. - Boswellic Acid - Boswellic Acid 3 Acetyl - - Boswellic Acid 3 Acetyl - - Boswellic Acid 11-keto - - Boswellic Acid 3 Acetyl -11- keto Boswellic Acid - AKBA Research data suggests that of the various boswellic acids, 3 Acetyl 11 keto Boswellic Acid or AKBA, is considered the most active and powerful acid. AKBA helps preserve the structural integrity of joint cartilage, promotes gastrointestinal health and maintains a healthy immune mediator cascade at the cellular level.

The Frankincense extract contains beta-boswellic acids (BA) 10 to 21%, 3-O-acetyle--boswellic acids (ABA) 0.05 to 6%, 11-oxo-b-boswellic acids (KBA) 2.5 to 7.5% and 3-Oacetyle-11-oxo-b-boswellic acids (AKBA) 0.1 to 3%. In conventional Boswellia of these major 6 Boswellic acids AKBA is present in the range of 0.1 to 3% only. Nutra Specialities India introduces AKMAX standardized to contain minimum 35% of AKBA.

5/25/2009

Highest Quality Standards

Specifications AKMAX Nutra Specialities India Off White to pale Yellow free flowing powder with a characteristic resinous taste. >90% >30% 50-150 mg/day Conventional Boswellia Serrata Extract Off White to pale Yellow free flowing powder with a characteristic resinous taste. >70% 2-3% 500-1500 mg/day

Color and Appearance

Organic Acid (Titration Method) AKBA (HPLC Method) Recommended Dosage

We also follow Pharmaceutical Standards in Consistent Quality Management. o o o o Water by KF Loss on Drying Heavy Metal Microbial Analysis

Biological Actions
Joint Support: Boswellia AKBA helps preserve the structural integrity of joint cartilage, promotes gastrointestinal health and maintains a healthy immune mediator cascade at the cellular level. Boswellia maintain healthy 5lipoxygenase (5LO) activity, moderating leukotriene biosynthesis and AKBA inhibit the leukotriene biosynthesis by a non-redox, noncompetitive inhibition of 5-LO. Immune Support: In addition to maintaining healthy 5LO activity, exciting new research has revealed that 5LO may influence healthy gene expression of immune compounds. In studies, 5LO has demonstrated the potential to support joint motility and comfort, in part by promoting a healthy immune response. It may also play a role in maintaining healthy matrix metalloproteinase (MMP) activity, supporting connective tissue structural composition. Gastrointestinal Support: A randomized double blind study revealed that AKBA supports gastrointestinal health. AKBA has also maintained healthy immune activity in the endothelial lining of the digestive tract. AKBA supports healthy cell signaling and cell cycle function for high capacity cellular support. A series of chronic inflammatory diseases are thought to be perpetuated by leukotrienes.

5/25/2009

AKBA Inhibits 5-Lipoxygenase and stops biosynthesis of Leukotrienes.

Name Chemical Formula Molecular Weight Melting Point CAS Number

: : : : :

3 Acetyl -11- keto Boswellic Acid C32H48O5 512.73 271 C 67416-61-9

Pathway of Boswellia AKBA

5/25/2009

Properties
The new improved AKMAX from Nutra extracts is potent in antiinflammatory action for enhanced results. This unique extract shall be employed in; the treatment of chronic inflammatory conditions such as Rheumatoid Arthritis, Chronic Bronchitis, Asthma, Chronic inflammatory bowel diseases (Ulcerative Colitis, Crohns Disease) as well as Chronic inflammatory skin diseases (Atopic Dermatitis and Psoriasis). In addition to maintaining healthy 5-LO activity, exciting new research has revealed that AKBA may influence healthy gene expression of immune compounds. In OA patients, AKBA controls and inhibits degeneration of cartilage tissue caused by the MMPs such as MMP-3 which are over-expressed and abundant in fluids of the synovial cavity.

The 5-LOX Paradox

The key enzyme in the conversion of Arachidonic Acid into LTB5 is 5-Lipoxygenase (5-LOX). Inhibition of 5-LOX thus assumes special significance when it comes to the management of chronic inflammatory disorders. Boswellic acids also act as efficient inhibitors of MAP Kinases & Topoisomerises. New studies show conclusively that 5-LOX products directly stimulate prostate cancer cell proliferation via several welldefined mechanisms.

5/25/2009

How 5-LOX Paradox - Works

Saturated and Omega-6 fats convert to Arachidonic acid in the body. One way that the body rids itself of excess arachidonic acid is provoking a dangerous metabolizing pathway through 5-lipoxygenase (5-LOX). Arachidonic acid is metabolized by 5-LOX to 5-hydroxyeicosatetraeonic acid (5-HETE), a potent survival factor that prostate cancer cells use to escape destruction. In addition to 5-HETE, 5-LOX also metabolizes arachidonic acid to leukotriene B4, a potent proinflammatory agent that causes destructive reactions throughout the body and inflicts severe damage to the arterial wall. In response to arachidonic acid overload, the body increases its production of enzymes like 5-LOX to degrade arachidonic acid. Not only do 5-LOX products directly stimulate cancer cell propagation, but the breakdown products that 5-LOX produces from arachidonic acid (such as leukotriene B4, 5-HETE, and hydroxylated fatty acids) cause tissue destruction, chronic inflammation, and increased resistance of tumor cells to apoptosis (programmed cell destruction).

5/25/2009

Other Benefits
Arthritis Respiratory System Disorders Gastro-Intestinal Tract Anti-Cancer

-- Its actions are very targeted -- It promotes Bone and Joint health

Arthritis
In Indian Ayurvedic medicine Boswellia serrata has been used for hundreds of years for treating Arthritis. Osteoarthritis (OA) affects nearly 21 million people in the USA, accounting for 25% of visits to primary care physicians. Extracts of Boswellia serrata have been clinically studied for Osteoarthritis (OA) and joint function, particularly for osteoarthritis of the knee As an anti-arthritic, AKMAX with AKBA reduces the chipping off of lycosaminoglycans, the base substance for cartilage repair unlike the commonly used NSAIDs and COX-2 inhibitors. AKMAX helps to shrink inflamed tissues by improving the blood supply to the affected area and enhances the repair of damaged blood vessels.

5/25/2009

Arthritis
A human study on patients with osteoarthritis of the knee showed that boswellia decreased pain, increasing physical functioning significantly in range of motion and endurance. Patients receiving AKBA treatment reported decrease in knee pain, increased knee flexion and increased walking distance. The frequency of swelling in the knee joint was decreased.

An inflamed knee joint that occurs in osteoarthritis.

Respiratory System Disorders

AKMAX inhibits Human Leukocyte Elastase (HLE) that causes Emphysema and stimulates mucus secretion leading to Cystic Fibrosis, Chronic Bronchitis, Bronchial Asthma etc. Bronchial Asthma is a disease of the lungs in which an obstructive ventilation disturbance of the respiratory passages evokes a feeling of shortness of breath. Bosellia serrata extract induces the activation of calpain in HeLa human cervical carcinoma cells.

5/25/2009

Inflammatory Bowel Diseases

Group of conditions which are inflammatory, affecting the tissue that lines the gastrointestinal system (the large and small intestine) is classed as an inflammatory bowel disease (IBD).

Animal studies shows significantly reduced macroscopic and microscopic inflammation.

Gastro-Intestinal Tract
AKMAX due to their inhibitory effects on 5-LOX exerts an antiinflammatory activity and is found to be useful in the treatment of Ulcerative Colitis and Crohns disease. Boswellia extracts cause immuno modulation by simultaneously inhibiting TH1 and promoting TH2 cytokine production. They regulate vascular responses to inflammation and stabilize mast cells. In cases of intestinal inflammation, boswellic acids may modulate the adhesive interactions between leukocytes and endothelial cells, by countering the activation of leukocytes and/or down-regulating the expression of endothelial cell adhesion molecules.

10

5/25/2009

Chronic Colitis
Colitis is a chronic digestive disease characterized by inflammation of the colon. The inflammatory process in colitis is associated with increased formation of leukotrienes. General signs and symptoms of colitis - Pain, depression, - Aches and pains within the joints, changes in bowel habits - Fever; swelling of the colon tissue, ulcers on the colon, - Diarrhea.

Anti-Cancer
All Boswellic acids have been shown to inhibit the growth of leukaemia cells in human leukaemia HL-60 in culture, in a dose dependent manner. Boswellic acids induce antiproliferation, differentiation and apoptosis in leukemia cell lines. They exert cytotoxic effects on established human glioblastoma and leukemia cell lines, as well as on primary human meningioma cells. Boswellic acids may help reduce cerebral edema in patients with brain tumors, helping reduce the need for steroids and their significant adverse side effects. Research show AKBA inhibited cellular growth in colon cancer cells. AKBA has also been found to inhibit tumor cell growth and induce Apoptosis.

11

5/25/2009

Anti-Cancer
AKBA can suppress STAT3 activation and has potential cancer therapeutic use. Cancer is a class of diseases in which a group of cells display uncontrolled growth.

A large invasive ductal carcinoma in a mastectomy specimen

Tissue can be organized in a continuous spectrum from normal to cancer.

Toxicity & Side Effects

Showed no pathological changes in haematological, biochemical or histological parameters at doses up to 1000 mg per kg. The LD-50 is > more than 2gm per kg. Another study showed that combining certain boswellic acid extracts with ethanol produced significant cellular toxicity, which was not observed in a sesame oil preparation. This finding underscores the importance of pursuing further research in phytopharmaceuticals to ensure their safe administration. Although veterinary patients are unlikely to imbibe ethanol voluntarily, they may encounter ethanol in other herbal extracts they are taking. Side effects of boswellic acids include abdominal discomfort nausea, epigastric pain, hyperacidity and diarrhea.

12

5/25/2009

Human Studies - Arthritis

Kimmatkar N, Thawani V, Hingorani L, Khiyani R.MS Orthopedics, Indira Gandhi Medical College, Nagpur, India. Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee--a randomized double blind placebo controlled trial. Phytomedicine. 2003 Jan;10(1):3-7 Trial:
To assess the efficacy, safety and tolerability of Boswellia Serratta Extract 30 Patients 250mg of Boswellia - decrease in knee pain, - increased knee flexion and - increased walking distance. - the frequency of swelling in the knee joint was decreased

Subject: Treatments: Outcome:

Human Studies - Arthritis

Sengupta K, Alluri KV, Satish AR, Mishra S, Golakoti T, Sarma KV, Dey D, Raychaudhuri SP., India., A double blind, randomized, placebo controlled study of the efficacy and safety of 30% AKBA for treatment of osteoarthritis of the knee. Arthritis Res Ther. 2008;10(4):R85. Epub 2008 Jul 30

Trial:

To evaluate the efficacy and safety of 30% AKBA in the treatment of osteoarthritis (OA) of the knee 75 Patients; 90 Day double-blind, randomized, placebocontrolled 100mg of Boswellia AKBA Significant improvements in pain score and functional ability in the AKBA admitted patients

Subject:

Treatments: Outcome:

13

5/25/2009

Animal Studies - Inflammatory

Krieglstein CF, Anthoni C, Rijcken EJ, Lauktter M, Spiegel HU, Boden SE,et al.Department of General Surgery, Westfalian Wilhelm's University, Waldeyerstrasse 1, 48149 Mnster, Germany. Acetyl-11-keto-beta-boswellic acid, a constituent of a herbal medicine from Boswellia serrata resin, attenuates experimental ileitis. Int J Colorectal Dis. 2001 Apr;16(2):88-95

Trial: Subject: Treatments: Outcome:

Leukocyte-endothelial cell interactions in inflammatory bowel disease on rats To determine the efficacy of Boswellia extract and AKBA Boswellia AKBA Both Boswellia extract and AKBA decreased rolling (up to 90%) and adherent leukocytes (up to 98%), attenuated tissue injury scores, and significantly reduced macroscopic and microscopic inflammation of the gut mucosa.

Human Studies - Inflammatory

Gupta I, Parihar A, Malhotra P, Gupta S, Ldtke R, Safayhi H, Ammon HP.Department of Medicine, Medical College Jammu, J&K, India. Effects of gum resin of Boswellia serrata in patients with chronic colitis. Planta Med. 2001 Jul;67(5):391-5

Trial:

The gum resin of Boswellia serrata and control for the treatment of chronic colitis disease. 20 for BSE and 10 for Control; 3 *300mg 6 weeks 900mg of Boswellia/daily 14 of 20 from BSE and 4 of 10 from control shown improvement in colitis

Subject: Treatments: Outcome:

14

5/25/2009

Human Studies - Inflammatory

Gupta I, Gupta V, Parihar A, Gupta S, Ldtke R, Safayhi H, Ammon HP.Pharmakologie fr Naturwissenschaftler, Pharmazeutisches Institut der Universitt Tbingen, Auf der Morgenstelle 8, D-72076 Tbingen, Germany. Effects of Boswellia serrata gum resin in patients with bronchial asthma: results of a double-blind, placebo-controlled, 6week clinical study. Eur J Med Res. 1998 Nov 17;3(11):511-4
Trial: Subject: Treatments: Outcome:
To treat Bronchial Asthma disease 40 for BSE 18-75 years; 3 *300mg 6 weeks and 40 for Control 14-58 years; 3 *300mg 6 weeks 900mg of Boswellia/daily; Double Blinded In BSE group shows 70% improvement in Asthma conditions and in control group only 27% showed improvements

Human Studies Anti-Cancer

Lu M, Xia L, Hua H, Jing Y. Division of Hematology/Oncology, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029-6547, USA. Acetyl-keto-beta-boswellic acid induces apoptosis through a death receptor 5-mediated pathway in prostate cancer cells. Cancer Res. 2008 Feb 15;68(4):1180-6

Trial:

The apoptotic effects and the mechanisms of action of AKBA to Induce Apoptosis in human prostate cancer cells.

Subject: Treatments: Outcome:

Human Prostate Cancer Cells

Boswellia AKBA/twice daily AKBA induces apoptosis in prostate cancer cells through a DR5-mediated pathway. AKBA resulted as a novel inhibitor in treatment of cancer cells.

15

5/25/2009

Boswellia Serrata AKBA

Corporate Office:
Nutra Specialities India No: 5, Vivekananda Street, Spurtank Road, Chetpet, Chennai 600 031,Tamil Nadu, India. Phone: +91 44 4284 9552 / 9553 Fax: +91 44 4284 9856 Email: marketing@nutraforlife.com

US Office:
Nutra for Life LLC 5100 Highlands Parkway, SE Smyrna, GA 30082 Dir: 1-770-373-5333 Phone: 1-770.916.1722 ext. 101 www.nutraforlife.com

16