Abstract
BackgroundLarge dose application of traditional Chinese medicines has attracted more and more attentions in recent years. However, the scientific connotation of large dose application has not been clarified so far. The present study was designed to investigate the protective effects of Chi-Dan-Tui-Huang decoction (CDTHD) against Alpha-naphthylisothiocyanate (ANIT) induced acute cholestatic hepatitis in rats and explore the dose-effect relationship of CDTHD as a reference for clinical application.MethodsThe administration of CDTHD at a series of doses was performed twice each day for 5 days. The acute cholestasic hepatitis models were induced by intragastric administration of ANIT on the third day of CDTHD administration. Then, the protective effects on cholestatic hepatitis were investigated by examining the following parameters: body weights of rats, morphological and histopathological liver changes, the levels of serum biomarkers including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, direct bilirubin and γ-glutamyltranspeptidase. Furthermore, the dose-effect relationship was investigated with the application of correspondence analysis.ResultIn the tested range of doses, CDTHD at the maximum tolerance dose did not show any toxicity as time went on. The efficacy result showed that CDTHD from 21.6 g/kg⋅d to 86.4 g/kg⋅d exhibited significant hepatoprotective effect against ANIT-induced acute cholestatic hepatitis. It alleviated liver injury and reversed adverse biochemical and histopathological changes in a dose-dependent manner. Correspondence analysis showed that Radix Paeoniae Rubra in CDTHD was the main effective component and CDTHD could enhance the integrated efficacy in dose-dependent manner.ConclusionsCDTHD is beneficial to liver protection in a dose-dependent manner. Especially large dose demonstrates potent efficacy and Radix Paeoniae Rubra in the formula contributes the main effect on ANIT-induced acute cholestatic hepatitis without toxicity.
Highlights
Large dose application of traditional Chinese medicines has attracted more and more attentions in recent years
Chi-Dan-Tui-Huang decoction (CDTHD) is beneficial to liver protection in a dose-dependent manner
Large dose demonstrates potent efficacy and Radix Paeoniae Rubra in the formula contributes the main effect on ANIT-induced acute cholestatic hepatitis without toxicity
Summary
Large dose application of traditional Chinese medicines has attracted more and more attentions in recent years. Chi-Dan-Tui-Huang decoction (CDTHD), serving as a famous decoction in cholestasis treatment, shows significant therapeutic effect in cholestasis [10,11]. It is composed of Radix Paeoniae Rubra, Salvia miltiorrhiza Bge, Trichosanthis Fructus and Puerariae Lobatae Radix. Radix Paeoniae Rubra has been frequently used at large dose for treatment of acute cholestatic hepatitis and a number of clinical cases have demonstrated the affirmative effectiveness of CDTHD [14,15,16]
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