The Inhibitory Effects of Herbal Components on CYP2C9 and CYP3A4 Catalytic Activities in Human Liver Microsomes

Abstract

Herbal medicines are widely consumed by patients in different clinical settings in the United States and all over the world. In this study, 7 herbal components ginsenosides Rb1, Rb2, Rc, and Rd (from ginseng quercetin) ginkgolides A and B (from ginkgo biloba) were investigated for their inhibitory effects on hepatic CYP2C9 and CYP3A4 catalytic activities in human liver microsomes. Tolbutamide 4-methylhydroxylation and testosterone 6beta-hydroxylation were used as index reactions of CYP2C9 or CYP3A4 catalytic activities, respectively. The metabolites of both reactions were measured by high-performance liquid chromatography and used as indicators of whether enzymes were inhibited or unaffected by these agents. Herbal components were studied at various concentrations (0.1, 1, 10, 100, 200 micromol/L). The herbal compounds investigated were capable of inhibiting CYP2C9 and CYP3A4 catalytic activities, but the potencies differed. Quercetin showed marked inhibitory effects on both tolbutamide 4-methylhydroxylation and testosterone 6beta-hydroxylation with IC(50) values of 35 and 38 micromol/L, respectively. Ginsenoside Rd also had significant inhibitory potency on both CYP2C9- and CYP3A4-mediated index reactions with IC(50) values of 105 and 62 micromol/L, respectively. Ginsenosides Rb1, Rb2, and Rc had limited inhibitory activities on both enzyme reaction systems, whereas the effects of ginkgolides A and B appeared negligible. It is concluded that the components of ginseng and ginkgo biloba screened are capable of inhibiting CYP2C9- and CYP3A4-mediated metabolic reactions. Our findings suggest that quercetin and ginsenoside Rd have the potential to interact with conventional medicines that are metabolized by CYP2C9 and CYP3A4 in vivo.

Herb — drug interaction of noni juice and Ginkgo biloba with phenytoin

“…Hence for each group. [60] and Numa et al, 2007 [61] proved that the active constituents of G. biloba have CYP2C9 inhibitory potential and the present results are in agreement with these reports. In contrast, our results are in contradictory to the results of Sugigyama et al, 2004 andUmegaki et al, 2002.…”

In Vitro Inhibition of Multiple Cytochrome P450 Isoforms by Xanthone Derivatives from Mangosteen Extract

“…The incidence of potential cytochrome P450 (P450)-mediated drug inhibition from herbal therapies has been noted for popular remedies such as St. John's wort, echinacea, ginseng, garlic, and saw palmetto (Obach, 2000;Foster et al, 2001;Chang et al, 2002;He and Edeki, 2004;Yale and Glurich, 2005;Liu et al, 2006;Modarai et al, 2007). Various herbal constituents have also been shown to induce P450 activity in vitro.…”

Effects of Herbal Extracts on the Function of Human Organic Anion-Transporting Polypeptide Oatp-B

“…For example, repetitive administration of St. John's wort decreases the blood concentrations of certain drugs, such as immunodepressants, by the induction of P450s (Piscitelli et al, 2000;Bauer et al, 2003). Some herbal extracts, such as ginkgo, echinacea, and soybean extracts, have been reported to inhibit P450s in vitro (He and Liu, 2002;Anderson et al, 2003;He and Edeki, 2004). We have reported that beverages such as green tea, which is processed into dietary supplements, inhibit the function of sulfotransferase (Nishimuta et al, 2005).…”