Increased involvement of Panax notoginseng in the mechanism of decreased hepatotoxicity induced by Tripterygium wilfordii in rats

Ethnopharmacological relevanceThe key problem with toxic Chinese herbs in clinical applications is how to find the most effective method to reduce toxicity. This study focuses on discussing the mechanism of decreased hepatotoxicity by the usage compatibility of two commonly used traditional Chinese drugs that are used clinically: Tripterygium wilfordii Hook. f. (TW) and Panax notoginseng (Burkill) F.H. Chen (PN). Additionally, based on the results from using metabonomics technology, the usage compatibility with these two herbs that was originated from clinical experience is the first to clarify the rationality of the drug combination.Materials and methodsThrough a fast and effective HPLC method, plasma concentration–time profiles and triptolide distribution characteristics in liver, heart, spleen, lung and kidney tissues were simultaneously determined in rats after oral administration of the aqueous extract of TW and TW-PN. The reduced hepatotoxicity data of the usage compatibility with TW and PN were also investigated, and then a UHPLC-QTOF/MS method was developed and validated for the explanation of the reduced hepatotoxicity mechanism.ResultsIt was indicated that nine endogenous metabolites might be potential biomarkers for hepatotoxicity induced by TW. In addition, the plasma concentration–time profiles and the distribution characteristics of TP in rats were changed after oral administration of the aqueous extract of TW-PN, and simultaneously, the hepatotoxicity was obviously decreased.ConclusionsThe results indicated that usage compatibility with TW and PN was reasonable in clinical use. To the best of our knowledge, this is the first report to describe the mechanism of reducing hepatotoxicity with the combined use of TW and PN from clinical experience.

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