Proteomics and network pharmacology of Ganshu Nuodan capsules in the prevention of alcoholic liver disease

Frontiers in Endocrinology

Endocrinology

Chen Dai¹  Guoliang Zhao²  Jing Zhang³  Lei Wang⁴  Yi Wu⁴  Kunhua Wei⁵  Xiaonan Yang⁵  Shuangshuang Qin⁵  Ying Liang⁵  Maobo Du⁶  Bingxue Zhou⁷  Zheng Jiang⁷  Zhaojing Luo⁷  Xuejie Cui⁸  Rachel Y. H. Yang⁹ 

[1] College of Life Sciences, Nanjing Agricultural University, Nanjing, China;Department of Gastroenterology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China;Department of Traditional Chinese Medicine, Shandong Mental Health Center, Shandong University, Jinan, Shandong, China;Department of Ultrasound, Shandong Provincial Hospital Affiliated To Shandong First Medical University, Jinan, China;Guangxi Key Laboratory of Medicinal Resources Protection and Genetic Improvement, National Engineering Research Center for Southwest Endangered Medicinal Resources Development, National Center for TCM Inheritance and Innovation, Guangxi Botanical Garden of Medicinal Plants, Nanning, China;Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China;Ministry of Education (MOE) Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China;Ministry of Education (MOE) Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China;College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China;Upper School, La Jolla Country Day School, La Jolla, CA, United States;

关键词: alcohol liver disease;    component identification;    molecular docking;    network pharmacology;    Proteomics;   

DOI  :  10.3389/fendo.2023.1229777

 received in 2023-05-27, accepted in 2023-07-25,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionGanshu Nuodan is a liver-protecting dietary supplement composed of Ganoderma lucidum (G. lucidum) spore powder, Pueraria montana (Lour.) Merr. (P. montana), Salvia miltiorrhiza Bunge (S. miltiorrhiza) and Astragalus membranaceus (Fisch.) Bunge. (A. membranaceus). However, its pharmacodynamic material basis and mechanism of action remain unknown.MethodsA mouse model of acute alcohol liver disease (ALD) induced by intragastric administration of 50% alcohol was used to evaluate the hepatoprotective effect of Ganshu Nuodan. The chemical constituents of Ganshu Nuodan were comprehensively identified by UPLC-QTOF/MS, and then its pharmacodynamic material basis and potential mechanism of action were explored by proteomics and network pharmacology.ResultsGanshu Nuodan could ameliorate acute ALD, which is mainly manifested in the significant reduction of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and malondialdehyde (MDA) content in liver and the remarkably increase of glutathione (GSH) content and superoxide dismutase (SOD) activity in liver. Totally 76 chemical constituents were identified from Ganshu Nuodan by UPLC-QTOF/MS, including 21 quinones, 18 flavonoids, 11 organic acids, 7 terpenoids, 5 ketones, 4 sterols, 3 coumarins and 7 others. Three key signaling pathways were identified via proteomics studies, namely Arachidonic acid metabolism, Retinol metabolism, and HIF-1 signaling pathway respectively. Combined with network pharmacology and molecular docking, six key targets were subsequently obtained, including Ephx2, Lta4h, Map2k1, Stat3, Mtor and Dgat1. Finally, these six key targets and their related components were verified by molecular docking, which could explain the material basis of the hepatoprotective effect of Ganshu Nuodan.ConclusionGanshu Nuodan can protect acute alcohol-induced liver injury in mice by inhibiting oxidative stress, lipid accumulation and apoptosis. Our study provides a scientific basis for the hepatoprotective effect of Ganshu Nuodan in acute ALD mice and supports its traditional application.

【 授权许可】

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Copyright © 2023 Yang, Wang, Cui, Zhang, Liang, Luo, Zhou, Jiang, Yang, Wu, Wei, Du, Qin, Dai and Zhao