Metabolism-mediated interaction potential of standardized extract of Tinospora cordifolia through rat and human liver microsomes.
OBJECTIVE
Tinospora cordifolia is used for treatment of several diseases in Indian system of medicine. In the present study, the inhibition potential of T. cordifolia extracts and its constituent tinosporaside to cause herb-drug interactions through rat and human liver cytochrome enzymes was evaluated.


MATERIALS AND METHODS
Bioactive compound was quantified through reverse phase high-performance liquid chromatography, to standardize the plant extracts and interaction potential of standardized extract. Interaction potential of the test sample was evaluated through cytochrome P450-carbon monoxide complex (CYP450-CO) assay with pooled rat liver microsome. Influence on individual recombinant human liver microsomes such as CYP3A4, CYP2D6, CYP2C9, and CYP1A2 isozymes was analyzed through fluorescence microplate assay, and respective IC50 values were determined.


RESULTS
The content of tinosporaside was found to be 1.64% (w/w) in T. cordifolia extract. Concentration-dependent inhibition was observed through T. cordifolia extract. Observed IC50 (μg/ml) value was 136.45 (CYP3A4), 144.37 (CYP2D6), 127.55 (CYP2C9), and 141.82 (CYP1A2). Tinosporaside and extract showed higher IC50 (μg/ml) value than the known inhibitors. T. cordifolia extract showed significantly less interaction potential and indicates that the selected plant has not significant herb-drug interactions relating to the inhibition of major CYP450 isozymes.


CONCLUSIONS
Plant extract showed significantly higher IC50 value than respective positive inhibitors against CYP3A4, 2D6, 2C9, and 1A2 isozymes. Consumption of T. cordifolia may not cause any adverse effects when consumed along with other xenobiotics.
['Bahadur|Shiv|S|', 'Mukherjee|Pulok K|PK|', 'Milan Ahmmed|S K|SK|', 'Kar|Amit|A|', 'Harwansh|Ranjit K|RK|', 'Pandit|Subrata|S|']
D000818:Animals D002248:Carbon Monoxide D065607:Cytochrome P-450 Enzyme Inhibitors D003577:Cytochrome P-450 Enzyme System D041743:Herb-Drug Interactions D006801:Humans D008862:Microsomes, Liver D010936:Plant Extracts D051381:Rats D031610:Tinospora
Tinospora cordifolia human liver microsome tinosporaside reverse phase high-performance liquid chromatography Cytochrome P450