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

BackgroundArishta 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).MethodologyExperimentally 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.ResultsAnimals 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.ConclusionThese 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.

Isolation, analysis and in vitro assessment of CYP3A4 inhibition by methylxanthines extracted from Pu-erh and Bancha tea leaves

Methylxanthines, purine alkaloids found in plants, are found in beverages (coffee, tea, cocoa) and foods (chocolate and other cocoa-containing foods) commonly consumed worldwide. Members of this family include caffeine, theophylline and theobromine. Methylxanthines have a variety of pharmacological effects, and caffeine and theophylline are used as pharmaceuticals. Methylxanthines are metabolized in the liver predominantly by the enzyme CYP1A2. Their co-administration with CYP1A2 inhibitors may lead to pharmacokinetic interactions. Little is known about the possible drug interactions between caffeine and substrates of other CYP450 enzymes. In our study, methylxanthine fractions inhibited CYP3A4 in a concentration-dependent manner. Concomitant consumption of green tea with CYP3A4 substrates could increase the possibility of interactions, and this requires further clarification. The inhibition of CYP3A4 is not only due to the presence of catechin derivatives but methylxanthines may also contribute to this effect.