Efficacy of Zhuyu Pill Intervention in a Cholestasis Rat Model: Mutual Effects on Fecal Metabolism and Microbial Diversity

ABSTRACT:

Cholestasis is a clinical condition resulting from the impairment of bile flow. Currently, patients with cholestasis still face several barriers in seeking diagnosis and treatment. Zhuyu Pill (ZYP) is an ancient classic formula of the Coptis-Evodia herb couples (CEHC), and has been used for cholestasis treatment in the clinic, however, its underlying biological mechanism in cholestasis remain to be clarified. In this study, a cholestasis rat model, induced by α-naphthyl-isothiocyanate (ANIT, 50mg/kg) and treated with ZYP (0.6g/kg or 1.2g/kg), was adopted. Serum biochemical indices and histopathological evaluation was performed, in addition to metabolomics analyses of fecal and 16S rDNA sequencing of the gut microbiota. We evaluated the anticholestatic activity of ZYP and investigated the mechanism underlying its correlation with gut microbiota and fecal metabolite regulation. The relationships between biochemical indices, fecal metabolites, and gut microbiota were analyzed. The results showed that both high and low doses of ZYP can effectively improve the blood biochemical parameters of cholestasis rats, and the intervention effect of high dose ZYP is superior to that that of lower dose. Based on a metabolomics test of fecal samples, significantly altered metabolites in the ANIT and ZYP treatment group were identified. In total, 734 metabolites were differentially expressed, and whose biological functions were mainly associated with amino acid metabolism, steroid hormone biosynthesis, and bile secretion. In addition, sequencing of the 16S rDNA unit in fecal samples revealed that the ZYP could improve the gut microbiota dysbiosis that ANIT had induced. Therefore, we conclude that ANIT altering of blood biochemical and metabolic profiles and gut microbiota can be effectively alleviated using ZYP treatment, this study contributes “TCM wisdom” to clinical diagnosis and treatment of cholestasis.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

SUBMITTER: Han Yu 

PROVIDER: MTBLS2721 | MetaboLights | 2022-05-30

REPOSITORIES: MetaboLights