A Study on the Therapeutic Efficacy of San Zi Yang Qin Decoction for Non-Alcoholic Fatty Liver Disease and the Underlying Mechanism Based on Network Pharmacology.
A Study on the Therapeutic Efficacy of San Zi Yang Qin Decoction for Non-Alcoholic Fatty Liver Disease and the Underlying Mechanism Based on Network Pharmacology.
复制标题
基于网络药理学的三子养秦汤治疗非酒精性脂肪肝的疗效及机制研究。
DOI：
10.1155/2021/8819245
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Song H
中科院分区：
文献类型：
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作者：
Li Y;Liu Y;Yang M;Wang Q;Zheng Y;Xu J;Zheng P;Song H
本研究以网络药理学为基础，结合体内实验，探讨三子养亲汤治疗非酒精性脂肪性肝病（NAFLD）的疗效及其可能机制。 根据化合物的药物相似性和靶点的二项分布，检索SZ的有效化学物质和靶点。使用通过GeneCards数据库、基因本体（GO）术语和京都基因和基因组百科全书（KEGG）途径筛选的NAFLD相关基因建立疾病-靶标-化学网络。并通过动物实验验证了网络药理学预测的SZ的疗效和作用机制。用高脂饲料喂养C57 BL/6 J小鼠22周建立NAFLD小鼠模型。对照组的小鼠用普通饲料喂养。从第23周开始，给NAFLD小鼠灌胃SZ或生理盐水8周。测定葡萄糖耐量后，处死小鼠，收集血清和肝组织。H&E染色观察肝组织病理变化。此外，检测丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、血清空腹血糖和胰岛素水平。ELISA法检测血清TNF-α水平，qRT-PCR法检测肝组织TNF-α水平。Western blot检测肝组织AKT的活化情况。 共筛选出SZ的27个有效成分和20个作用靶点。GO分析发现SZ和NAFLD的靶点之间存在显著相关性。KEGG分析显示SZ和NAFLD中富集的信号通路包括NAFLD、TNF-α和凋亡通路。主要GO和KEGG途径的曲线下面积表明SZ在改善NAFLD中的潜在作用。体内实验表明，SZ能显著减轻NAFLD小鼠肝脂肪变性和肝组织炎性细胞浸润，降低血清转氨酶，改善胰岛素抵抗和糖耐量。SZ可上调磷酸化AKT的蛋白水平。此外，SZ治疗明显降低了NAFLD小鼠血清和肝组织中TNF-α的水平。 根据网络药理学分析和体内实验，SZ对NALFD具有治疗作用。其机制主要涉及胰岛素抵抗、TNF-α和细胞凋亡等相关通路。本研究结果为SZ治疗NAFLD提供了科学依据。
This study aims to explore the therapeutic efficacy of San Zi Yang Qin Decoction (SZ) and its potential mechanism in the treatment of non-alcoholic fatty liver disease (NAFLD) based on network pharmacology and in vivo experiments. Effective chemicals and targets of SZ were searched in online databases, according to the drug-likeness of compounds and the binomial distribution of targets. A disease-target-chemical network was established using NAFLD-associated genes screened through GeneCards database, Gene Ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Furthermore, animal experiments were conducted to verify the efficacy and mechanism of SZ predicted by network pharmacology. The NAFLD mouse model was established with C57BL/6J mice fed with a high-fat diet for 22 weeks. The mice in the control group were fed with a chow diet. From the 23rd week, the NAFLD mice were treated with intragastric SZ or normal saline for 8 weeks. After the glucose tolerance was measured, the mice were sacrificed, followed by the collection of serum and liver tissues. Pathological changes in liver tissues were examined by H&E staining. Additionally, alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum fast blood glucose, and insulin levels were detected. Expression levels of TNF-α of serum and liver tissues were determined by ELISA and qRT-PCR, respectively. Western blot was used to detect the activation of AKT in liver tissues. A total of 27 effective compounds and 20 targets of SZ were screened. GO analysis uncovered a significant correlation between the targets of SZ and those of NAFLD. KEGG analysis presented the signaling pathways enriched in SZ and NAFLD, including NAFLD, TNF-α, and apoptosis pathways. The area under the curve of major GO and KEGG pathways indicated the potential role of SZ in improving NAFLD. In vivo experiments demonstrated that SZ significantly alleviated hepatosteatosis and inflammatory cell infiltration in liver tissues, reduced serum transaminases, and improved insulin resistance and glucose tolerance of NAFLD mice. The protein level of phospho-AKT was upregulated by SZ. Additionally, SZ treatment obviously impaired the TNF-α level in the serum and liver tissue of NAFLD mice. According to the network pharmacology analysis and in vivo experiments, SZ could have therapeutic efficacy for NALFD. The mechanism mainly involves pathways relative to insulin resistance, TNF-α, and apoptosis. Our results provide a scientific basis for SZ in the clinical treatment of NAFLD.
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DOI：
10.1016/j.bbalip.2018.08.004
发表时间：
2018-10
期刊：
Biochimica et biophysica acta. Molecular and cell biology of lipids
影响因子：
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作者：
Feng S;Dai Z;Liu AB;Huang J;Narsipur N;Guo G;Kong B;Reuhl K;Lu W;Luo Z;Yang CS
通讯作者：
Yang CS
影响因子：
5.6
作者：
Kanuri G;Bergheim I
通讯作者：
Bergheim I
影响因子：
82.9
作者：
Friedman SL;Neuschwander-Tetri BA;Rinella M;Sanyal AJ
通讯作者：
Sanyal AJ
非酒精性脂肪肝疾病（NAFLD） - 对药物代谢酶和转运蛋白的发病机理，分类和影响。
影响因子：
5.9
作者：
Cobbina E;Akhlaghi F
通讯作者：
Akhlaghi F
影响因子：
21.8
作者：
通讯作者：
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