Exploring the Mechanism of Modified Zexie Decoction Against Metabolic Associated Fatty Liver Disease Based on Network Pharmacology and Experimental Validation.

IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS
Pengyan Shi, Xiaoying Chen, Jiangtao Cao, Zhe Feng, Boyu Xue
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Abstract

Introduction/objective: The incidence of metabolic-associated fatty liver disease (MAFLD) increases annually. Modified Zexie Decoction (MZXD) can treat this disease; however, their mechanisms of action are uncertain. This study evaluated the mechanisms of MZXD against MAFLD based on network pharmacology, molecular docking, and in vivo experiments.

Methods: The main active compounds, targets and signaling pathways of MZXD against MAFLD were obtained using network pharmacological analysis. Underlying mechanisms were validated by molecular docking and in vivo assays.

Results: Forty-one active ingredients and 197 intersection targets were identified. The main active ingredients include quercetin, luteolin, isorhamnetin, 3-methylhexane, and 3β- acetoxyatractylone. The main targets were TP53, JUN, HSP90AA1, MAPK1, MAPK3, AKT1, NF-κB p65, TNF, ESR1, FOS, and IL-6. The pathway enrichment analysis indicated that MZXD was related to the IL-17, TNF, and PI3K-AKT signaling pathways. Molecular docking suggested that these active ingredients bound strongly to TNF, IL-6, and NF-κB p65, which are integral components of the TNF pathway. In the rat MAFLD model, MZXD attenuated high-fat diet( HFD)-induced liver injury and lipid accumulation, decreased the serum levels of the inflammatory mediators TNF-α, IL6, and IL-1β, and inhibited the protein expression of TNF-α, IL6, p- IKB-α and p-NF-κB p65. Furthermore, immunohistochemistry results showed that MZXD attenuated the F4/80 staining intensity of the liver compared with the model group.

Conclusion: Collectively, our results suggested that MZXD could improve MAFLD by downregulating TNF/NF-κB signaling mediated macrophage activation.

基于网络药理学和实验验证的改良泽泻煎剂防治代谢相关性脂肪肝的机制探索
导言/目的:代谢相关性脂肪肝(MAFLD)的发病率逐年上升。改良泽泻煎剂(MZXD)可以治疗这种疾病,但其作用机制尚不确定。本研究基于网络药理学、分子对接和体内实验,评估了改良泽泻煎剂抗脂肪肝的作用机制:方法:通过网络药理学分析获得了MZXD抗MAFLD的主要活性化合物、靶点和信号通路。结果:41个有效成分和197个信号通路被发现:结果:确定了 41 种有效成分和 197 个交叉靶点。主要活性成分包括槲皮素、木犀草素、异鼠李素、3-甲基己烷和 3β- 乙酰氧基白术酮。主要靶标为 TP53、JUN、HSP90AA1、MAPK1、MAPK3、AKT1、NF-κB p65、TNF、ESR1、FOS 和 IL-6。通路富集分析表明,MZXD 与 IL-17、TNF 和 PI3K-AKT 信号通路有关。分子对接表明,这些有效成分与 TNF、IL-6 和 NF-κB p65 有很强的结合力,而 TNF、IL-6 和 NF-κB p65 是 TNF 通路的组成部分。在大鼠MAFLD模型中,MZXD减轻了高脂饮食(HFD)诱导的肝损伤和脂质蓄积,降低了血清中炎症介质TNF-α、IL6和IL-1β的水平,抑制了TNF-α、IL6、p-IKB-α和p-NF-κB p65的蛋白表达。此外,免疫组化结果显示,与模型组相比,MZXD可减轻肝脏中F4/80的染色强度:总之,我们的研究结果表明,MZXD可通过下调TNF/NF-κB信号介导的巨噬细胞活化改善MAFLD。
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来源期刊
CiteScore
3.10
自引率
5.60%
发文量
327
审稿时长
7.5 months
期刊介绍: Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews/mini-reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal: Target identification and validation Assay design, development, miniaturization and comparison High throughput/high content/in silico screening and associated technologies Label-free detection technologies and applications Stem cell technologies Biomarkers ADMET/PK/PD methodologies and screening Probe discovery and development, hit to lead optimization Combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries) Chemical library design and chemical diversity Chemo/bio-informatics, data mining Compound management Pharmacognosy Natural Products Research (Chemistry, Biology and Pharmacology of Natural Products) Natural Product Analytical Studies Bipharmaceutical studies of Natural products Drug repurposing Data management and statistical analysis Laboratory automation, robotics, microfluidics, signal detection technologies Current & Future Institutional Research Profile Technology transfer, legal and licensing issues Patents.
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