Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510000, China.
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China.
Chin J Nat Med. 2020 Mar;18(3):211-218. doi: 10.1016/S1875-5364(20)30023-6.
Cholestasis is caused by the obstacle of bile formation or secretion and can develop into severe liver diseases. We previously reported the ethanol extract of Schisandra sphenanthera (Wuzhi tablet, WZ) can significantly protect against lithocholic acid (LCA)-induced intrahepatic cholestasis in mice, partially due to the activation of PXR pathway and promotion of liver regeneration. However, the effect of WZ on the bile acids profile and gut microbiome in cholestastic mice remain unknown. In this study, the effect of WZ against LCA-induced liver injury was evaluated and its effect on the bile acids metabolome and gut microbiome profiles in cholestastic mice was further investigated. Targeted metabolomics analysis was performed to examine the change of bile acids in the serum, liver, intestine and feces. The change of intestinal flora were detected by the genomics method. Targeted metabolomics analysis revealed that WZ enhanced the excretion of bile acids from serum and liver to intestine and feces. Genomics analysis of gut microbiome showed that WZ can reverse LCA-induced gut microbiome disorder to the normal level. In conclusion, WZ protects against LCA-induced cholestastic liver injury by reversing abnormal bile acids profiles and alteration of gut microbiome.
胆汁淤积是由胆汁形成或分泌障碍引起的，并可发展为严重的肝脏疾病。我们之前报道过五味子醇提物（五酯片，WZ）可显著减轻胆酸（LCA）诱导的小鼠肝内胆汁淤积，部分原因是激活了 PXR 通路并促进了肝再生。然而，WZ 对胆汁淤积小鼠的胆汁酸谱和肠道微生物组的影响尚不清楚。在本研究中，评估了 WZ 对 LCA 诱导的肝损伤的作用，并进一步研究了其对胆汁淤积小鼠胆汁酸代谢组和肠道微生物组谱的影响。采用靶向代谢组学分析方法检测血清、肝脏、肠道和粪便中胆汁酸的变化。采用基因组学方法检测肠道菌群的变化。靶向代谢组学分析显示，WZ 增强了胆汁酸从血清和肝脏向肠道和粪便的排泄。肠道微生物组的基因组学分析表明，WZ 可以将 LCA 诱导的肠道微生物组紊乱逆转至正常水平。总之，WZ 通过逆转异常的胆汁酸谱和肠道微生物组的改变来保护 LCA 诱导的胆汁淤积性肝损伤。
