关键词: 肩周炎, 2型糖尿病, 葛根麻芪方, 网络药理学, 分子对接, 分子动力学, 炎症因子, 胰岛素, β-谷甾醇

Abstract: BACKGROUND: Gegenmaqi prescription has a good effect on periarthritis of shoulder combined with type 2 diabetes and has a good application prospect, but the specific mechanism is not clear. 
OBJECTIVE: To explore the action mechanism of Gegenmaqi prescription on periarthritis of shoulder and type 2 diabetes by network pharmacology, molecular docking, and molecular dynamics. 
METHODS: The active components and protein targets of Gegenmaqi prescription were retrieved from the Traditional Chinese Medicine System Pharmacology database and analysis platform, referred to as TCMSP jointly established by the Shanghai Institute of Materia Medica, Chinese Academy of Sciences and the Institute of Chinese Materia Medica, and China Academy of Chinese Medical Sciences in 2013. Genecards created by Professor Doron Lancet’s team at the Weizmann Institute of Science in Israel in 1997, Drugbank created by scientists at the University of Alberta in Canada in 2006, and the OMIM database established by Dr. Victor A. McKusick’s team at Johns Hopkins University in the United States in 1966 were used to search the disease protein targets of periarthritis of shoulder and type 2 diabetes, and the intersection targets were obtained based on the WeChat online tool. The protein-protein interaction network was constructed based on the STRING database created in 2000 by Peer Bork’s team at the European Bioinformatics Institute (EMBL), and the protein-protein interaction relationship was analyzed. The core targets were screened according to the degree value. The intersection targets were subjected to GO and KEGG enrichment analyses. Finally, molecular docking and molecular dynamics simulation were used to verify the binding of key components to key targets. 
RESULTS AND CONCLUSION: (1) One hundred and forty-two active ingredients of Gegenmaqi prescription were obtained, including 65 intersections between component targets and disease targets, 5 key active ingredients (β-sitosterol, stigmasterol, kaempferol, quercetin, and formononetin), and 5 key targets (AKT1, tumor necrosis factor, interleukin-10, JUN, and TP53). (2) GO function enrichment included 508 items, 390 biological process items, 77 molecular function items and 41 cell component items. KEGG pathway analysis showed 146 pathways, mainly involving advanced glycation end products receptor signaling pathway, lipid and atherosclerosis signaling pathway, tumor necrosis factor signaling pathway, and interleukin-17 signaling pathway. (3) Molecular docking showed that the key components and key targets had good binding activity. Molecular dynamics simulation showed that β-sitosterol had stable interactions with AKT1, tumor necrosis factor and interleukin 10. (4) Gegenmaqi prescription has been comprehensively studied, and the material basis of its pharmacological effect has been primarily clarified. It is predicted that Gegenmaqi prescription can treat periarthritis of shoulder combined with type 2 diabetes through multi-components, multi-targets, and multi-pathways to exert anti-inflammatory and regulate insulin secretion. 

Key words: periarthritis of shoulder, type 2 diabetes mellitus, Gegenmaqi prescription, network pharmacology, molecular docking, molecular dynamics, inflammatory factors, insulin, β-sitosterol