Evaluation of subacute toxicity and herb-drug interaction potential of an herbal Arishta formulation

Background Arishta technology is an age-old heritage and uses herbal decoctions to prepare self-generated alcoholic medicines. In Ayurveda, Arishta preparations are widely used as a remedy for metabolic disorders. However, their safety and influence on herb metabolism pathways were not yet explored. Aim: To study the subacute toxicity of a polyherbal Arishta formulation (coded as DB-07) in rats and to evaluate its potential for inhibition of the drug-metabolizing enzyme (Cytochrome P450 3A4). Methodology Experimentally naive rats were treated with graded oral doses of DB-07 (10 and 20 mL/kg/day) for 28 days. During the course of the experiment, all the animals were closely observed for apparent behavioural abnormalities and mortalities. Tissue histology was performed to assess any sign of toxicity. In addition, in vitro CYP3A4 inhibition assay was performed to study the effect on drug metabolism pathways. Results Animals did not show any change in body weight, organ toxicity and food consumption throughout the dosing period of 28 days. Pathophysiological, behavioural status and locomotor activity were not altered. DB-07 did not inhibit CYP3A4 enzyme and drug metabolism pathway in-vitro. Gallic acid and quercetin were identified as phytomarker from the formulation that may be responsible for its activity related safety issue. Conclusion These results indicate that use of DB-07 may be safe with no sign of toxicity for up to 28 days in rats. Further, CYP3A4 inhibition assay indicated that DB-07 is less likely to have herb-drug interactions when concomitantly administered with CYP3A4 inhibitors or inducer.