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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.
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 and and novel approach for assessing HDI in integrative medicine The case studies 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. Ha lf 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