Effects of Ayurvedic Rasayana botanicals on CYP3A4 isoenzyme system

• Published in: Journal of integrative medicine Vol. 13; no. 3; pp. 165 - 172
• Main Authors: Borse, Swapnil P., Kamble, Bhagyashree B.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-05-2015
• Subjects: Animals; Asparagus Plant; Asparagus racemosus; Ayurveda; Chromatography, High Pressure Liquid; cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A - metabolism; Cytochrome P-450 CYP3A Inhibitors - pharmacology; drugs, Chinese herbal; Gymnema sylvester; Gymnema sylvestre; Herb-Drug Interactions; IC50; Isoenzymes - antagonists & inhibitors; plant extracts; Plant Extracts - pharmacology; Rats; Rats, Wistar; 半数抑制浓度; 植物药; 水提取物; 草药植物; 药物相互作用; 酶系统; 高效液相色谱法; Ayurveda; cytochrome P-450 CYP3A; Asparagus racemosus; plant extracts; drugs, Chinese herbal; Gymnema sylvester; herb-drug interactions
• ISSN: 2095-4964
• DOI: 10.1016/S2095-4964(15)60173-X

OBJECTIVE： 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.METHODS： 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.RESULTS： ARE and GSE showed no inhibition with IC50 values 〉1 000 μg/m L while the standard inhibitor ketoconazole completely abolished CYP3A4-dependent activity at 0.531 μg/m L and IC50 was found to be 0.036 μg/m L.CONCLUSION： 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.