ETHNOPHARMACOLOGICAL RELEVANCE: 'Triphala' is one of the age-old, most commonly used polyherbal preparation from Ayurveda as Rasayana drug. AIM OF THE STUDY: This study was aimed at evaluating the effect of 'Triphala' on drug modulating enzymes to assess its safety through its potential to interact with co-administered drugs. MATERIALS AND METHODS: The cytochrome P450 inhibitory effect of 'triphala' formulation was investigated on rat liver microsomes using CYP450-CO complex assay and on individual isoform such as CYP3A4 and 2D6 using fluorescence screening. RP-HPLC method was developed to standardize 'triphala' and its individual components using gallic acid as analytical marker compound. RESULTS: RP-HPLC analysis demonstrated the presence of gallic acid (4.30±2.09 mg/g) in the formulation. The formulation showed 23% inhibition of the rat liver microsomes through CYP450-CO complex assay which is comparatively less when compared with the individual components. Further, the effect of standardized formulation dissolved in ethanol showed CYP3A4 and CYP2D6 inhibitory activity at the IC(50) values of 119.65±1.91 μg/ml and 105.03±0.98 μg/ml respectively. Gallic acid was also found to inhibit both the isoforms at the IC(50) values of 87.24±1.11 μg/ml and 92.03±0.38 μg/ml respectively. CONCLUSIONS: Various concentrations of the formulation and its individual components showed significantly less inhibitory activity (p<0.001) on individual isoforms when compared with the positive control. Assessment on the in vitro effect of 'triphala' on drug modulating enzymes has important implications for predicting the likelihood of herb-drug interactions if these are administered concomitantly.
ETHNOPHARMACOLOGICAL RELEVANCE: 'Triphala' is one of the age-old, most commonly used polyherbal preparation from Ayurveda as Rasayana drug. AIM OF THE STUDY: This study was aimed at evaluating the effect of 'Triphala' on drug modulating enzymes to assess its safety through its potential to interact with co-administered drugs. MATERIALS AND METHODS: The cytochrome P450 inhibitory effect of 'triphala' formulation was investigated on rat liver microsomes using CYP450-CO complex assay and on individual isoform such as CYP3A4 and 2D6 using fluorescence screening. RP-HPLC method was developed to standardize 'triphala' and its individual components using gallic acid as analytical marker compound. RESULTS: RP-HPLC analysis demonstrated the presence of gallic acid (4.30±2.09 mg/g) in the formulation. The formulation showed 23% inhibition of the rat liver microsomes through CYP450-CO complex assay which is comparatively less when compared with the individual components. Further, the effect of standardized formulation dissolved in ethanol showed CYP3A4 and CYP2D6 inhibitory activity at the IC(50) values of 119.65±1.91 μg/ml and 105.03±0.98 μg/ml respectively. Gallic acid was also found to inhibit both the isoforms at the IC(50) values of 87.24±1.11 μg/ml and 92.03±0.38 μg/ml respectively. CONCLUSIONS: Various concentrations of the formulation and its individual components showed significantly less inhibitory activity (p<0.001) on individual isoforms when compared with the positive control. Assessment on the in vitro effect of 'triphala' on drug modulating enzymes has important implications for predicting the likelihood of herb-drug interactions if these are administered concomitantly.