Effects of Kampo Medicines on CYP and P-gp Activity in Vitro

Abstract

The Kampo medicines are more and more often used in recent years, usually together with the Western drugs. The need for the investigation of drug interactions between Kampo medicines and Western drugs are, therefore, widely recognized. In the present study, the effects of 3 Kampo medicines (Rikkunshito, Yokukansan and Boiogito) on the activity of cytochrome P450 (CYP), a superfamily of drug-metabolizing enzymes, were investigated in an in vitro study using human CYP recombinants. Their effects on the P-glycoprotein (P-gp), one of the major drug transporters, were also evaluated by the ATPase assay using human P-gp membranes and verapamil as a substrate. The inhibition rate of Rikkunshito, Yokukansan and Boiogito on human CYP3A4, 2C9, 2C19, 2D6 and 2E1 was less than 50% at the concentrations below 0.1 mg/ml except for the inhibition of CYP2D6 by Boiogito. Furthermore, none of the Kampo medicines affected the ATPase activity at the concentrations lower than 0.1 mg/ml, either in the absence or presence of verapamil, indicating their low inhibitory potency against P-gp. These findings indicate that Rikkunshito, Yokukansan and Boiogito are unlikely to cause clinically relevant drug interactions involving the inhibition of major CYP isozymes and P-gp.

Cytochrome P450 inhibitory potential of Triphala—A Rasayana from Ayurveda

“…Several natural products have been studied for its activity on DME and have been reported by several researchers (Tepy et al, 2006). Further, several literature were also available on the effect of DME on several systems of medicines including traditional Chinese medicines (Foster et al, 2002), North American botanicals (Scott et al, 2006), Indonesian medicinal plants (Tepy et al, 2006), Japanese Kampo medicines (Ito et al, 2008) and Cuba/Mexican medicinal plants (Rodeiro et al, 2009). Large proportion of Indian population relies on the use of traditional medicines for their primary health care needs (Mukherjee and Wahile, 2006).…”

Inhibitory effects of wogonin on catalytic activity of cytochrome P450 enzyme in human liver microsomes

“…The majority of these interactions involve cytochrome P450 (CYP450). Several herbs and natural remedies have already been reported to induce or inhibit CYP450 enzymes (Ito et al 2008;Usia et al 2006;Madgula et al 2009;Oleson et al 2004;Sekiguchi et al 2008). CYP 450 enzymes are one of the major Phase I enzymes involved in the metabolism of drugs and other xenobiotics, as well as some endogenous substrates (Xu et al 2008).…”

Beneficial Effects of Rikkunshito, a Japanese Kampo Medicine, on Gastrointestinal Dysfunction and Anorexia in Combination with Western Drug: A Systematic Review

“…The effects of rikkunshito on the activity of cytochrome P450 (CYP), a superfamily of drug-metabolizing enzymes, and P-glycoprotein (P-gp), a major drug transporter, were investigated by Ito et al [60]. The inhibition rate of rikkunshito on human CYP3A4, 2C9, 2C19, 2D6, and 2E1 was less than 50% at concentrations below 0.1 mg/mL.…”