Acute and chronic toxicity, cytochrome p450 enzyme inhibition, and HERG channel blockade studies with a polyherbal, ayurvedic formulation for inflammation.

Debendranath Dey,Nitin Athavale,Sunetra Chaskar,Deepa Chitre

doi:10.1155/2015/971982

Abstract

Ayurvedic plants are known for thousands of years to have anti-inflammatory and antiarthritic effect. We have recently shown that BV-9238, a proprietary formulation of Withania somnifera, Boswellia serrata, Zingiber officinale, and Curcuma longa, inhibits LPS-induced TNF-alpha and nitric oxide production from mouse macrophage and reduces inflammation in different animal models. To evaluate the safety parameters of BV-9238, we conducted a cytotoxicity study in RAW 264.7 cells (0.005–1 mg/mL) by MTT/formazan method, an acute single dose (2–10 g/kg bodyweight) toxicity study and a 180-day chronic study with 1 g and 2 g/kg bodyweight in Sprague Dawley rats. Some sedation, ptosis, and ataxia were observed for first 15–20 min in very high acute doses and hence not used for further chronic studies. At the end of 180 days, gross and histopathology, blood cell counts, liver and renal functions were all at normal levels. Further, a modest attempt was made to assess the effects of BV-9238 (0.5 µg/mL) on six major human cytochrome P450 enzymes and 3H radioligand binding assay with human hERG receptors. BV-9238 did not show any significant inhibition of these enzymes at the tested dose. All these suggest that BV-9238 has potential as a safe and well tolerated anti-inflammatory formulation for future use.

Highlights

Modern medical pharmacotherapy is based on extensive testing and validation of efficacy and safety utilizing various methodologies
The traditional Ayurvedic science of medicine is known to use single or multiple plant combinations, especially for chronic conditions. These plant extracts usually consist of hundreds of active ingredients or molecules
There is a need to apply modern methodologies to study and validate the safety of traditional herbs or plants and their combinations by a more extensive approach. This was a modest effort to study a formulation consisting of multiple standardized Ayurvedic plant extracts, for safety in in vitro and in vivo testing methods by modern pharmaceutical standards

Summary

Introduction

Modern medical pharmacotherapy is based on extensive testing and validation of efficacy and safety utilizing various methodologies. Complementary and Alternative Medicine (CAM) is rapidly becoming a viable option to modern pharmacotherapy for a multitude of chronic ailments These include degenerative and inflammatory bone and joint conditions such as osteoarthritis and rheumatoid arthritis [3]. The traditional Ayurvedic science of medicine is known to use single or multiple plant combinations, especially for chronic conditions These plant extracts usually consist of hundreds of active ingredients or molecules. There is a need to apply modern methodologies to study and validate the safety of traditional herbs or plants and their combinations by a more extensive approach This was a modest effort to study a formulation consisting of multiple standardized Ayurvedic plant extracts, for safety in in vitro and in vivo testing methods by modern pharmaceutical standards

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Conclusion