Protective Effect of Modified Suanmei-Tang on Metabolic-Associated Fatty Liver Disease: An Integrated Strategy of Network Pharmacology, Metabolomics, and Transcriptomics.

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL Drug Design, Development and Therapy Pub Date : 2024-11-13 eCollection Date: 2024-01-01 DOI:10.2147/DDDT.S478072

Chao Wang, Mei Zhao, Yuanyuan Yue, Chao Hu, Chunqiu Zhou, Zhongyi Zhang, Yunliang He, Yaqi Luo, Tao Shen, Sijie Dang, Yang Yang, Yong Zhang

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Abstract

Background: Modified Suanmei-Tang (MST) comprises four plants common to both traditional Chinese medicine and culinary applications, and it can potentially alleviate metabolic-associated fatty liver disease (MAFLD) triggered by a high-fat diet (HFD).

Purpose: This research aims to investigate the impact and underlying mechanisms of MST in ameliorating MAFLD caused by an HFD.

Methods: UHPLC-Q-Orbitrap-MS/MS was used to determine the constituents of MST and to evaluate its effects on MAFLD mouse models. Transcriptomics, network pharmacology, and bioinformatics analysis (including Kyoto Encyclopedia of Genes and Genomes and Gene Set Enrichment Analysis) were utilized to further clarify the mechanisms by which MST acts on MAFLD. The experimental methods included ELISA, real time quantitative PCR (RT-qPCR), Western blot, immunohistochemistry, molecular docking, and metabolomics. Transcriptomics was integrated with metabolomics to find correlations between differentially expressed genes and metabolites, and crucial genes were validated through RT-qPCR.

Results: A total of 23 components of MST were identified. The formulation was found to alleviate metabolic disorders, obesity, insulin resistance, inflammation, and oxidative stress in mice with MAFLD. The findings indicate that MST promoted autophagy by suppressing phosphorylation in the PI3K/AKT/mTOR pathway and enhancing lipid management in the livers of MAFLD mice.

Conclusion: MST could effectively improve lipid metabolism disorders and liver lipid deposition in MAFLD mice, and its mechanism might be related to regulating the PI3K/AKT/mTOR pathway to improve autophagy.

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改良川梅汤对代谢相关性脂肪肝的保护作用：网络药理学、代谢组学和转录组学的综合策略。

背景：目的：本研究旨在探讨改良川味汤（MST）在改善由高脂饮食（HFD）引起的代谢相关性脂肪肝（MAFLD）方面的影响及其潜在机制：方法：采用 UHPLC-Q-Orbitrap-MS/MS 测定 MST 的成分，并评估其对 MAFLD 小鼠模型的影响。利用转录组学、网络药理学和生物信息学分析（包括京都基因与基因组百科全书和基因组富集分析）进一步阐明了 MST 对 MAFLD 的作用机制。实验方法包括ELISA、实时定量PCR（RT-qPCR）、Western印迹、免疫组化、分子对接和代谢组学。转录组学与代谢组学相结合，寻找差异表达基因与代谢物之间的相关性，并通过 RT-qPCR 验证关键基因：结果：共鉴定出 23 种 MST 成分。结果：共鉴定出 23 种 MST 成分，发现该配方能缓解 MAFLD 小鼠的代谢紊乱、肥胖、胰岛素抵抗、炎症和氧化应激。研究结果表明，MST 通过抑制 PI3K/AKT/mTOR 通路中的磷酸化促进自噬，并增强 MAFLD 小鼠肝脏中的脂质管理：结论：MST能有效改善MAFLD小鼠的脂质代谢紊乱和肝脏脂质沉积，其机制可能与调节PI3K/AKT/mTOR通路改善自噬有关。

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.