In vitro Inhibitory Effect of Gymnema sylvestre Extracts and Total Gymnemic Acids Fraction on Select Cytochrome P450 Activities in Rat Liver Microsomes.

BACKGROUND AND OBJECTIVES: Gymnema sylvestre R. Br. is a well-known Indian medicinal herb. Gymnemic acids are pentacyclic triterpenes saponins and active phytoconstituents of Gymnema sylvestre. The study aimed at evaluation of the in vitro rat liver cytochrome P450 (CYP) inhibition potential of extracts and total gymnemic acid (TA)-enriched fractions from G. sylvestre.

METHODS: Standardization of G. sylvestre [ethanolic (EL), hydroethanolic (HE), total acid of ethanolic (TAE), total acid of hydroethanolic (TAHE) and total acid of aqueous (TAAQ) extract] was done with respect to deacyl gymnemic acid (DAGA), using reverse phase-high performance liquid chromatography (RP-HPLC). Total triterpenoid content was determined by vanillin perchloric acid assay.

RESULTS: Total triterpene content was found to be the highest in TAAQ (59.86 ± 0.005% w/w) and TAE (49.77 ± 0.009% w/w). TAAQ showed IC50  ≤ 50 µg/ml for all selected CYP activities. Testosterone 6β-hydroxylation was strongly inhibited by TAE (IC50 : 15.48 ± 2.13 µg/ml) and was moderately by TAAQ and EL with IC50  ≥ 50 µg/ml. Flurbiprofen 4'-hydroxylation was subject to strong, weak and moderate inhibition by TAAQ (IC50 : 34.67 ± 1.38 µg/ml), TAE (IC50 : ≥ 50 µg/ml) and EL (IC50 : > 50 µg/ml), respectively. Dextromethorphan O-demethylation was inhibited by TAHE and TAAQ.

CONCLUSIONS: In vitro inhibition studies suggested that TA strongly inhibits activity of selected CYP. This inhibition may possibly be due to triterpenoids and gymnemic acids that have been reported to be present in it. Data also suggest a potential for possible in vivo herb-drug interactions involving G. sylvestre and other medications that are metabolized by the same CYP.