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Inhibition of LPS-Induced TNF-{Alpha} and NO Production in Mouse Macrophage and Inflammatory Response in Rat Animal Models by a Novel Ayurvedic Formulation, BV-9238

Significant statement

Bone and joint disorders are the number one cause of disability in the world today. Conventional pharmacotherapy consists of NSAIDs, COX-2 inhibitors, steroids, and the biologics. Each of these has significant side effects. The biologics work primarily by inhibiting cytokines such as Tumor Necrosis Factor-Alpha, Interleukin-1beta and Interleukin-6. Today, the biologics are used widely in all inflammatory disorders including rheumatoid arthritis (RA), Crohns disease, psoriasis, COPD and others. However, these agents have significant and potentially life threatening side effects such as reactivation of tuberculosis and malignancies. Besides, the availability and cost of treatment; and logistics of injections and their potential hazards, make these a challenge to use all over the world. . ^BV-9238 was developed from the traditional science of Ayurveda. Native to India, Ayurveda describes the use of plants and sometimes minerals, to treat difficult to treat disorders in humans and animals. 4,000 year old textbooks have detailed descriptions of the part of the plant to be used, the way it is to be processed, combinations, metabolism and kinetics to the final effect at receptor level.

BV-9238 is a natural formulation of four specialized plant extracts that work synergistically for bone/joint and immune conditions. Each extraction is conducted by a proprietary US patented method that yields higher concentration of bio-active compounds, yet keeping them natural, effective and very safe. We have studied the product in double-blind placebo-controlled Phase-II clinical trials in osteoarthritis (Chopra et al, J Clin Rheumatol 2004; 10: 236–245) and in rheumatoid arthritis (Chopra et al, J Rheumatol 2000; 27:1365-72). The RA study showed sero-conversion of Rheumatoid factor, and significant improvement in C-Reactive protein and Interleukin-6.

The current work was an attempt to study the mechanism of action of this multi-herb natural product using modern parameters. We found that BV-9238 is a potent TNF-Alpha and Nitric-oxide inhibitor. We further studied in animal models of adjuvant induced arthritis and rat paw edema and found significant reduction of inflammation. Other validation studies using modern pharmaceutical guidelines such as acute and chronic toxicity, other in-vivo pharmacology, hERG channel and Cytochrome P450 studies have been conducted with documentation of efficacy and safety. BV-9238 shows promise as an alternate, safe and effective therapy in disorders where TNF-alpha and NO play a role.  The Company seeks licensing and partnership opportunities worldwide for commercialization of this product (ARTREX®) as a natural supplement or OTC healthcare.

 

Journal Reference

Dey D, Chaskar S, Athavale N, Chitre D.

Phytother Res. 2014 Oct;28(10):1479-85.

Bioved Pharmaceuticals Pvt. Ltd., BAIF Bhawan, Z Wing, Warje Malwadi, Pune, 411 052, India.

Abstract

Rheumatoid arthritis is a chronic crippling disease, where protein-based tumor necrosis factor-alpha (TNF-{Alpha}) inhibitors show significant relief, but with potentially fatal side effects. A need for a safe, oral, cost-effective small molecule or phyto-pharmaceutical is warranted. BV-9238 is an Ayurvedic poly-herbal formulation containing specialized standardized extracts of Withania somnifera, Boswellia serrata, Zingiber officinale and Curcuma longa. The anti-inflammatory and anti-arthritic effects of BV-9238 were evaluated for inhibition of TNF-{Alpha} and nitric oxide (NO) production, in lipopolysaccharide-stimulated, RAW 264.7, mouse macrophage cell line. BV-9238 reduced TNF-{Alpha} and NO production, without any cytotoxic effects. Subsequently, the formulation was tested in adjuvant-induced arthritis (AIA) and carrageenan-induced paw edema (CPE) rat animal models. AIA was induced in rats by injecting Freund’s complete adjuvant intra-dermally in the paw, and BV-9238 and controls were administered orally for 21 days. Arthritic scores in AIA study and inflamed paw volume in CPE study were significantly reduced upon treatment with BV-9238. These results suggest that the anti-inflammatory and anti-arthritic effects of BV-9238 are due to its inhibition of TNF-{Alpha}, and NO, and this formulation shows promise as an alternate therapy for inflammatory disorders where TNF-{Alpha} and NO play important roles. Copyright © 2014 John Wiley & Sons, Ltd.

Copyright © 2014 John Wiley & Sons, Ltd.

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Inhibition of LPS-Induced TNF-{Alpha} and NO Production in Mouse Macrophage and Inflammatory Response in Rat Animal Models by a Novel Ayurvedic Formulation, BV-9238