Multi-omics joint analysis reveals that the Miao medicine Yindanxinnaotong formula attenuates non-alcoholic fatty liver disease

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2024-09-21 DOI:10.1016/j.phymed.2024.156026

Lei Huang , Qing Rao , Chaoyan Wang , Yu Mou , Xiuyan Zheng , Enming Hu , Jiang Zheng , Yanmei Li , Lin Liu

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Abstract

Backgroud

Non-alcoholic fatty liver disease (NAFLD) is a growing chronic liver disease worldwide, and no effective agent is approved yet for this condition. Traditional Chinese Medicine (TCM), which has been practiced for thousands of years in China and other Asian countries, is considered an important source for identifying novel medicines for various diseases. Miao medicine Yindanxinnaotong formula (YDX) is a classical TCM for the treatment of hyperlipidemia disease by reducing blood lipid content, while the role of YDX have not been clarified in NAFLD.

Purpose

To investigate the protective effect of YDX on NAFLD in mice induced by high fat diet (HFD) and clarify the potential mechanism.

Methods

NAFLD mice model was constructed by receiving HFD for 10-week period with or without YDX administration. Lipid profiles, biochemical indicators, and histopathological staining were performed to evaluate the extent of hepatic lipid accumulation and hepatic steatosis. 16S rRNA sequencing was used to determine the gut microbial composition. Serum metabolomics was further used to investigate the changes in plasma biomarkers for NAFLD-associated by UPLC-Q-TOF/MS analysis. Subsequently, liver transcriptomics was employed to identify differentially expressed genes and explore regulatory pathways. Then, lipid metabolism–related proteins and inflammation factors were examined by Western blot and ELISA.

Results

YDX reduced body weight gain, liver index and inflammatory cytokines levels, along with improved hepatic steatosis, serum lipid profile, sensitivity to insulin and also tolerance to glucose, and enhanced oxidative defense system in HFD-induced mice. Also, YDX remarkedly affected gut microbiota diversity and community richness and decreased the ratio of Firmicutes/Bacteroidetes. Meanwhile, YDX also reduced the production of harmful lipid metabolites in the sera of NAFLD mice, such as LPC(18:0), LPC(18:1) and carnitine. Notably, consistent with liver transcriptomics results, YDX downregulated the expression of proteins implicated in de novo lipid synthesis (Srebp-1c, Acaca, Fasn, Scd-1, and Cd36) and pro-inflammatory cytokines (IL-6 and TNF-α), and increased the expression of proteins-related fatty acid β-oxidation (Ampkα, Ppar-α, and Cpt-1) in the liver by activating Ampk pathway.

Conclusion

YDX is promisingly an effective therapy for preventing NAFLD by modulating the Ampk pathway, inhibiting gut microbiota disorder, and reducing the production of harmful lipid metabolites.

Abstract Image

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多组学联合分析发现，苗药银丹新诺通配方可减轻非酒精性脂肪肝。

背景介绍非酒精性脂肪肝（NAFLD）是全球范围内日益严重的慢性肝病，目前尚无有效药物获准用于治疗该病。中医在中国和其他亚洲国家已有数千年的历史，被认为是发现治疗各种疾病的新药的重要来源。目的：研究 YDX 对高脂饮食（HFD）诱导的小鼠非酒精性脂肪肝的保护作用，并阐明其潜在机制：方法：构建非酒精性脂肪肝小鼠模型。方法：对小鼠进行为期 10 周的高密度脂蛋白胆固醇饮食（HFD），同时给药或不给药 YDX，建立非酒精性脂肪肝小鼠模型，通过血脂谱、生化指标和组织病理学染色来评估肝脏脂质堆积和肝脏脂肪变性的程度。16S rRNA 测序用于确定肠道微生物组成。通过UPLC-Q-TOF/MS分析，进一步利用血清代谢组学研究非酒精性脂肪肝相关血浆生物标志物的变化。随后，利用肝脏转录组学鉴定差异表达基因并探索调控通路。然后，通过Western印迹和ELISA检测脂质代谢相关蛋白和炎症因子：结果：YDX 降低了高密度脂蛋白胆固醇诱导小鼠的体重增加、肝脏指数和炎症细胞因子水平，改善了肝脂肪变性、血清脂质状况、对胰岛素的敏感性和对葡萄糖的耐受性，并增强了氧化防御系统。此外，YDX 还显著影响了肠道微生物群的多样性和群落丰富度，降低了固醇菌/类杆菌的比例。同时，YDX 还能减少非酒精性脂肪肝小鼠血清中有害脂质代谢物的产生，如 LPC(18:0)、LPC(18:1) 和肉碱。值得注意的是，与肝脏转录组学结果一致，YDX通过激活Ampk通路，下调了肝脏中与脂质从头合成有关的蛋白（Srebp-1c、Acaca、Fasn、Scd-1和Cd36）和促炎细胞因子（IL-6和TNF-α）的表达，并增加了与脂肪酸β氧化有关的蛋白（Ampkα、Ppar-α和Cpt-1）的表达：结论：YDX 通过调节 Ampk 通路、抑制肠道微生物群紊乱和减少有害脂质代谢产物的产生，有望成为预防非酒精性脂肪肝的有效疗法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.