Involvement of herb–herb interactions in the influences of Radix Scutellaria and Coptis Chinensis on the bioavailability of the anthraquinones form Rhei Rhizoma in rats

Xiexin decoction (XXD) is composed of Rhei Rhizoma (DH), Radix Scutellaria (HQ), and Coptis Chinensis (HL). Free anthraquinones in DH are the basic effective constituents in XXD. Reportedly, HL decreases the bioavailability of the anthraquinones, while HQ antagonizes the effect of HL. In this study, we aimed to determine the underlying mechanisms. The metabolisms of anthraquinones by intestinal flora were studied using rat fecal suspension (RFS); the metabolisms of rhein (a typical anthraquinone in DH) by rat intestine and liver were studied using rat intestine microsomes (RIMs) and rat liver microsomes (RLMs), respectively; the intestinal transport of rhein was studied using everted gut sacs. The results showed that HL decreased the amount of the free anthraquinones after incubation in RFS and inhibited the intestinal transport of rhein, but HQ antagonized the effect of HL. On the other hand, HQ strongly inhibited the glucuronidation of rhein in both RIMs and RLMs. The results suggested that HL decreased the oral bioavailability of the anthraquinones due to inhibiting the conversion of conjugated anthraquinones to free anthraquinones by intestinal flora and decreasing the intestinal transport of the anthraquinones; HQ confronted the effect of HL by inhibiting the glucuronidation of the anthraquinones in intestine and weakening the inhibitory effects of HL.