穿心莲内酯对非酒精性脂肪性肝炎(NASH)的药理机制研究:基于网络药理学的生物信息学方法
Investigating pharmacological mechanisms of andrographolide on non-alcoholic steatohepatitis (NASH): A bioinformatics approach of network pharmacology.
作者信息
Li Lei, Li Sheng-He, Jiang Jin-Peng, Liu Chang, Ji Li-Li
机构信息
Key Laboratory of Quality & Safety Control for Pork, Ministry of Agriculture and Rural, Anhui Key Laboratory of Animal Nutritional Regulation and Health, College of Animal Science, Anhui Science and Technology University, Fengyang 233100, China.
Shanghai Key Laboratory of Compound Chinese Medicines, MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
出版信息
Chin Herb Med. 2021 May 13;13(3):342-350. doi: 10.1016/j.chmed.2021.05.001. eCollection 2021 Jul.
OBJECTIVE
To investigate the mechanisms of andrographolide against non-alcoholic steatohepatitis (NASH) based on network pharmacology, so as to provide a reference for further study of andrographolide in the treatment of NASH and other metabolic diseases.
METHODS
The methionine- and choline-deficient (MCD) diet-induced NASH mice were treated by administration of andrographolide, and serum transaminase and pathological changes were analyzed. The network pharmacology-based bioinformatic strategy was then used to search the potential targets, construct protein-protein interaction (PPI) network, analyze gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment, and conduct molecular docking to explore the molecular mechanisms.
RESULTS
The predicted core targets TNF, MAPK8, IL6, IL1B and AKT1 were enriched in non-alcoholic fatty liver disease (NAFLD) signaling pathway and against NASH by regulation of fatty acids synthesis, anti-inflammation and anti-oxidation.
CONCLUSION
This work provides a scientific basis for further demonstration of the anti-NASH mechanisms of andrographolide.
目的
基于网络药理学探讨穿心莲内酯抗非酒精性脂肪性肝炎(NASH)的作用机制,为穿心莲内酯治疗NASH及其他代谢性疾病的深入研究提供参考。
方法
采用蛋氨酸和胆碱缺乏(MCD)饮食诱导的NASH小鼠,给予穿心莲内酯进行治疗,分析血清转氨酶及病理变化。然后运用基于网络药理学的生物信息学策略查找潜在靶点,构建蛋白质-蛋白质相互作用(PPI)网络,分析基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集情况,并进行分子对接以探索分子机制。
结果
预测的核心靶点TNF、MAPK8、IL6、IL1B和AKT1富集于非酒精性脂肪性肝病(NAFLD)信号通路,通过调节脂肪酸合成、抗炎和抗氧化作用对抗NASH。
结论
本研究为进一步阐明穿心莲内酯抗NASH机制提供了科学依据。