Synergistic effects of rhubarb-gardenia herb pair in cholestatic rats at pharmacodynamic and pharmacokinetic levels

Ethnopharmacological relevanceHerb pair serves as the basic building block of a traditional Chinese medicine (TCM) formula. The rhubarb–gardenia herb pair (RGHP), composed of rhubarb and gardenia, has meaningful clinical effects to cure cholestasis diseases. This study was designed to confirm the expected synergistic effects of RGHP at pharmacodynamic and pharmacokinetic levels.Materials and methodsThirty male Sprague-Dawley rats were divided into control, model and drug-treated groups. After intragastrically administrated with α-naphthylisothiocyanate (ANIT) to induce cholestasis, rats were treated with rhubarb, gardenia or RGHP. For pharmacodynamic study, biochemical and histopathological tests were performed to assess the hepatoprotective effects. While for pharmacokinetic study, a LC–MS method was developed for determination of five main chemical markers, namely genipin, rhein, aloe emodin, emodin and chrysophanol in rat plasma.ResultsThe biochemical and histopathological tests suggested that RGHP exerted enhanced hepatoprotective effects against the ANIT-induced cholestasis compared with single herbs. The pharmacokinetic study indicated RGHP could significantly elevate systemic exposure level and prolong retention time of five markers in comparison with rhubarb or gardenia alone.ConclusionsThe present study demonstrated the synergistic effects of RGHP in ANIT-induced cholestatic rats at pharmacodynamic and pharmacokinetic levels, and has significant enlightenments for the rational use of the related TCM formulas containing RGHP.

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