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Abstract: Ethnopharmacological relevance: Rhizoma coptidis is used as an antidysenteric in clinics in China. However, patients suffering from dysentery are susceptible to the acute toxicity of Rhizoma coptidis. The current study investigates the effects of lipopolysaccharide (LPS), which are a key pathogenic factor in dysentery, on the acute toxicity of a Rhizoma coptidis extract in mice; possible mechanisms are proposed. Materials and methods: Acute toxicity and pharmacokinetic experiments in mice were conducted. The plasma concentration of Rhizoma coptidis alkaloids in mice was determined using liquid chromatography/tandem mass spectrometry. The activity of acetylcholinesterase (AChE) in the tissue homogenate was determined using an AChE determination kit. Results: Pretreatment with LPS for 16h increased the acute toxicity of the oral Rhizoma coptidis extract. Systemic exposure to Rhizoma coptidis alkaloids was also increased by LPS pretreatment. Neostigmine significantly increased whereas pyraloxime methylchloride reduced the acute toxicity of the Rhizoma coptidis extract. LPS pretreatment alone showed no significant effect on the activity of thoracoabdominal diaphragm AChE. However, it enhanced the inhibitory effect of the Rhizoma coptidis extract. LPS pretreatment did not affect the acute toxicity of various dosages of tail vein-injected berberine. Conclusions: LPS increased the acute toxicity of the oral Rhizoma coptidis extract in mice by increasing the systemic exposure to the Rhizoma coptidis alkaloids. [Copyright &y& Elsevier]

Abstract: Aim of the study: To ascertain the effective constituents in Xiexin Decoction for anti-inflammation and the interactions of these constituents at the pharmacodynamic level. Materials and Methods: Rats were administered oral Xiexin Decoction 1h before intraperitoneal lipopolysaccharide. Nitric oxide production and Xiexin Decoction constituents in venous serum samples were quantified and the correlation between nitric oxide production and each constituent in serum was calculated. Raw264.7 cells were stimulated with lipopolysaccharide and one or more Xiexin Decoction constituents; cell viability and nitric oxide production was quantified. Results: Xiexin Decoction significantly decreased nitric oxide production in vivo, which correlated well with rhein, baicalin, emodin and aloe-emodin. All the typical constituents of Xiexin Decoction, with the exception of physcione and chrysophanol, dose-dependently inhibited nitric oxide production in vitro. In an orthogonal designed in vitro study, rhein was the most powerful constituent, followed by baicalin then berberine and no synergy was found among these constituents. Conclusions: Rhein was the most effective anti-inflammatory constituent in Xiexin Decoction followed by baicalin; no synergy was observed between rhein, baicalin and berberine at the pharmacodynamic level in vitro. [Copyright &y& Elsevier]