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

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 (3)H 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.

• Authors: Debendranath Dey, Sunetra Chaskar, Nitin Athavale, Deepa Chitre
• Journal: BioMed research international (Biomed Res Int) Vol. 2015 Pg. 971982 ( 2015) ISSN: 2314-6141 [Electronic] United States
• PMID: 25893199 (Publication Type: Journal Article)

Chemical References

• Cytochrome P-450 Enzyme Inhibitors
• ERG1 Potassium Channel
• Ether-A-Go-Go Potassium Channels
• KCNH2 protein, human
• Lipopolysaccharides
• Plant Preparations
• Tumor Necrosis Factor-alpha
• Nitric Oxide
• Cytochrome P-450 Enzyme System

Topics

• Animals
• Cell Line
• Cytochrome P-450 Enzyme Inhibitors (chemistry, pharmacology)
• Cytochrome P-450 Enzyme System (metabolism)
• ERG1 Potassium Channel
• Ether-A-Go-Go Potassium Channels (antagonists & inhibitors, metabolism)
• Female
• Humans
• Inflammation (chemically induced, drug therapy, metabolism, pathology)
• Lipopolysaccharides (toxicity)
• Macrophages (metabolism, pathology)
• Male
• Mice
• Nitric Oxide (metabolism)
• Plant Preparations (chemistry, pharmacology)
• Plants, Medicinal (chemistry)
• Rats
• Tumor Necrosis Factor-alpha (metabolism)