Phytomedicine : international journal of phytotherapy and phytopharmacology · 2025
Yuzhuo Zhixiao pill can treat non-alcoholic steatohepatitis through modulation of gut microbiota, bile acid and short-chain fatty acid metabolism.
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Du Yuanqin, Xu Jian, Jia Juhong, Nong Yaobin, Lin Yong, Ye Yixian, Zhong Yuexue, Tan Qinwen, Wei Yanfei, Huang Guihua, Mao Dewen, Huang Guochu, Lu Lu, Peng Yujiao, Huang Hongna, Huang Jingjing
Аннотация
BACKGROUND: Yuzhuo Zhixiao Pill (YZZXP), a formulation in traditional Chinese medicine (TCM), exhibits therapeutic potential in non-alcoholic steatohepatitis (NASH). However, the mechanisms underlying its effects, particularly those involving gut microbiota-bile acid-short-chain fatty acid (GM-BA-SCFA) interactions, remain unclear. Current therapies present notable side effects and inadequately address the multifactorial etiology of NASH.
PURPOSE: To evaluate the anti-NASH efficacy of YZZXP and elucidate its mechanism, focusing on GM remodeling and BA/SCFA regulation.
STUDY DESIGN: This study established a NASH model in rats using a high-fat diet (HFD) and performed fecal microbiota transplantation (FMT) experiments.
METHODS: The therapeutic impacts of YZZXP on gut microbial structure (16S rDNA sequencing), SCFA concentrations, and BA profiles (analyzed by LC-MS and GC-MS) were assessed.
RESULTS: YZZXP administration alleviated HFD-induced obesity, hepatic steatosis, inflammatory responses, and disturbances in glycolipid metabolism. Microbial profiling via 16S rDNA sequencing revealed restored gut microbial diversity, marked by increased Akkermansia, Bacteroides, and Roseburia abundance. PROB and FMT interventions validated GM modulation as central to YZZXP 's effects. Targeted metabolomic analyses demonstrated elevated levels of SCFAs (notably butyrate and acetate) and substantial shifts in BA composition, accompanied by downregulation of intestinal FXR-FGF19 signaling and enhanced cholesterol excretion.
CONCLUSIONS: YZZXP exerts anti-NASH activity through a synergistic mechanism comprising GM restoration, BA metabolic reprogramming via FXR pathway inhibition, and SCFA-driven metabolic modulation. In contrast to monotherapy approaches, the multi-target strategy of YZZXP prevents compensatory dysbiosis and yields more durable metabolic benefits than PROB or FMT alone. By integrating microbiota-metabolite interplay into therapeutic design, YZZXP introduces a novel paradigm in traditional medicine for NASH management, addressing the limitations of synthetic agents while promoting metabolic homeostasis.
PURPOSE: To evaluate the anti-NASH efficacy of YZZXP and elucidate its mechanism, focusing on GM remodeling and BA/SCFA regulation.
STUDY DESIGN: This study established a NASH model in rats using a high-fat diet (HFD) and performed fecal microbiota transplantation (FMT) experiments.
METHODS: The therapeutic impacts of YZZXP on gut microbial structure (16S rDNA sequencing), SCFA concentrations, and BA profiles (analyzed by LC-MS and GC-MS) were assessed.
RESULTS: YZZXP administration alleviated HFD-induced obesity, hepatic steatosis, inflammatory responses, and disturbances in glycolipid metabolism. Microbial profiling via 16S rDNA sequencing revealed restored gut microbial diversity, marked by increased Akkermansia, Bacteroides, and Roseburia abundance. PROB and FMT interventions validated GM modulation as central to YZZXP 's effects. Targeted metabolomic analyses demonstrated elevated levels of SCFAs (notably butyrate and acetate) and substantial shifts in BA composition, accompanied by downregulation of intestinal FXR-FGF19 signaling and enhanced cholesterol excretion.
CONCLUSIONS: YZZXP exerts anti-NASH activity through a synergistic mechanism comprising GM restoration, BA metabolic reprogramming via FXR pathway inhibition, and SCFA-driven metabolic modulation. In contrast to monotherapy approaches, the multi-target strategy of YZZXP prevents compensatory dysbiosis and yields more durable metabolic benefits than PROB or FMT alone. By integrating microbiota-metabolite interplay into therapeutic design, YZZXP introduces a novel paradigm in traditional medicine for NASH management, addressing the limitations of synthetic agents while promoting metabolic homeostasis.