Yuzhuo Zhixiao pill can treat non-alcoholic steatohepatitis through modulation of gut microbiota, bile acid and short-chain fatty acid metabolism

IF 8.3 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-09-28 DOI:10.1016/j.phymed.2025.157348

Yuanqin Du , Jian Xu , Juhong Jia , Yaobin Nong , Yong Lin , Yixian Ye , Yuexue Zhong , Qinwen Tan , Yanfei Wei , Guihua Huang , Dewen Mao , Guochu Huang , Lu Lu , Yujiao Peng , Hongna Huang , Jingjing Huang

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引用次数: 0

Abstract

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.

Abstract Image

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玉炙止消丸可通过调节肠道菌群、胆酸和短链脂肪酸代谢来治疗非酒精性脂肪性肝炎。

背景：玉炙止消丸（YZZXP）是一种中药制剂，具有治疗非酒精性脂肪性肝炎（NASH）的潜力。然而，其作用机制，特别是涉及肠道微生物-胆汁酸-短链脂肪酸（GM-BA-SCFA）相互作用的机制仍不清楚。目前的治疗方法存在明显的副作用，并且不能充分解决NASH的多因素病因。目的：评价YZZXP抗nash的疗效并阐明其作用机制，重点探讨其对GM重塑和BA/SCFA的调控作用。研究设计：本研究采用高脂肪饮食（HFD）大鼠建立NASH模型，并进行粪便微生物群移植（FMT）实验。方法：评估YZZXP对肠道微生物结构（16S rDNA测序）、SCFA浓度和BA谱（LC-MS和GC-MS分析）的治疗作用。结果：YZZXP可减轻hfd诱导的肥胖、肝脂肪变性、炎症反应和糖脂代谢紊乱。16S rDNA测序显示肠道微生物多样性恢复，Akkermansia、Bacteroides和Roseburia丰度增加。PROB和FMT干预验证了转基因调节是YZZXP效果的核心。有针对性的代谢组学分析表明，SCFAs（尤其是丁酸盐和醋酸盐）水平升高，BA组成发生实质性变化，伴随着肠道FXR-FGF19信号的下调和胆固醇排泄的增强。结论：YZZXP发挥抗nash活性的协同机制包括GM恢复、通过FXR通路抑制BA代谢重编程和scfa驱动的代谢调节。与单药治疗方法相比，YZZXP的多靶点策略可防止代偿性生态失调，并比单独使用PROB或FMT产生更持久的代谢益处。通过将微生物群-代谢物相互作用整合到治疗设计中，YZZXP为NASH治疗引入了传统医学的新范式，解决了合成药物的局限性，同时促进了代谢稳态。

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.