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Abstract: Ethnopharmacological relevance: Rhizoma coptidis is a traditional Chinese medicine with pharmacological properties. It is usually prescribed with Fructus evodiae as traditional Chinese medicine (TCM) formulas. Here we report the influences of Fructus evodiae on the pharmacokinetics of the Rhizoma coptidis alkaloids and propose possible mechanisms. Materials and methods: Pharmacokinetic experiments were performed in rats. In vitro absorption experiments were performed in everted rat gut sacs, while in vitro metabolism experiments and determination of hepatic UDP-glucuronosyltransferase (UGT) 1A1 mRNA expression were performed in rat liver microsomes. Results: Pretreatment with Fructus evodiae extract for two weeks decreased the systemic exposure of the Rhizoma coptidis alkaloids. This effect was not due to inhibition of absorption or enhanced hepatic phase I metabolism of the Rhizoma coptidis alkaloids. However, Fructus evodiae pretreatment enhanced both the activity and expression of hepatic UGT1A1. Conclusions: The results showed that Fructus evodiae pretreatment decreased the systemic exposure of the Rhizoma coptidis alkaloids by inducing hepatic UGT1A1. [Copyright &y& Elsevier]

Aim of the study: Rhizoma Coptidis (Huanglian) is a widely used Traditional Chinese Medicine. However, it causes human as well as animal toxicities. In this study, we aimed to ascertain the toxic constituents in Rhizoma Coptidis. Materials and methods: The acute toxicity of both the total extract and the alkaloid-rich extract of Rhizoma Coptidis were tested in mice. The dose related tissue concentration of the Rhizoma Coptidis alkaloids in mice was determined using high performance liquid chromatography with ultraviolet detection. The influence of phenobarbital sodium [a non-selective hepatic enzyme (P450) inducer] on the acute toxicity of Rhizoma Coptidis as well as the tissue concentration of the alkaloids was investigated. The cytotoxicity of the Rhizoma Coptidis alkaloids was tested in six cell lines using the MTT assay. Results: The median acute oral lethal dose of the total extract of Rhizoma Coptidis was 2.95g/kg in mice. The alkaloid-rich extract was much more toxic than the total extract of Rhizoma Coptidis. Four Rhizoma Coptidis alkaloids were detected in brain, heart, and lung tissues of mice that received the oral total extract of Rhizoma Coptidis. Tissue concentration increased nonlinearly with higher doses. Phenobarbital sodium decreased the tissue concentration of every alkaloid as well as the toxicity of Rhizoma Coptidis. All alkaloids, especially berberine, showed dose and time dependent cytotoxicity. Conclusions: The toxic constituents of Rhizoma Coptidis were the alkaloids, mainly berberine. [Copyright &y& Elsevier]