1.Effects of Ayurvedic Rasayana botanicals on CYP3A4 isoenzyme system.
Swapnil P BORSE ; Bhagyashree B KAMBLE
Journal of Integrative Medicine 2015;13(3):165-172
<b>OBJECTIVEb>Consuming botanical dietary supplements or herbal drugs along with prescription drugs may lead to potential pharmacokinetic-pharmacodynamic (PK-PD) herb-drug interactions (HDI). The present study focuses on the importance of and novel approach for assessing HDI in integrative medicine with case examples of two frequently-used Ayurvedic Rasayana botanicals.
<b>METHODSb>The aqueous extracts of Asparagus racemosus (ARE) and Gymnema sylvester (GSE) were prepared as per Ayurvedic Pharmacopoeia of India. Chemoprofiling of these extracts was done using high-performance liquid chromatography (HPLC). Additionally, ARE was characterized for the presence of shatavarins IV and I using HPLC & mass spectroscopy respectively. Effects of ARE and GSE were investigated on rat liver microsome using testosterone probe drug assay. The changes in formation of metabolite (6-β hydroxy testosterone) were monitored on incubation of testosterone alone, testosterone with ketoconazole, ARE and GSE using HPLC. Half inhibitory concentration (IC50) was used to predict plausible HDI.
<b>RESULTSb>ARE and GSE showed no inhibition with IC50 values >1 000 μg/mL while the standard inhibitor ketoconazole completely abolished CYP3A4-dependent activity at 0.531 μg/mL and IC50 was found to be 0.036 μg/mL.
<b>CONCLUSIONb>ARE and GSE prepared as per Ayurvedic Pharmacopoeia of India were found to be safe for CYP3A4-mediated inhibitory HDI in rats. Our in vitro study suggests the need of further in vivo investigation for HDI in order to provide clinical relevance.
Animals ; Asparagus Plant ; Chromatography, High Pressure Liquid ; Cytochrome P-450 CYP3A ; metabolism ; Cytochrome P-450 CYP3A Inhibitors ; pharmacology ; Gymnema sylvestre ; Herb-Drug Interactions ; Isoenzymes ; antagonists & inhibitors ; Plant Extracts ; pharmacology ; Rats ; Rats, Wistar