基于网络药理学分析及分子对接技术探讨牛膝单药防治强直性脊柱炎的作用机制

摘要/Abstract

摘要： 目的应用网络药理学、分子对接技术解析牛膝单药治疗强直性脊柱炎（ankylosing spondylitis,AS）的潜在机制。方法利用中药系统药理学技术平台TCMSP得到牛膝的化学成分,通过Swiss Target Prediction数据库搜索得到牛膝活性成分相对应的靶点,再通过GeneCards数据库、Drugbank数据库和Disgenet数据库来收集AS相关靶点。借助Venny 2.1取得药物组分治疗疾病的交集靶点,即为牛膝治疗AS的潜在靶点。利用Cytoscape软件,生成牛膝治疗AS的蛋白互作（Protein-protein interaction,PPI）网络。将交集靶点导入DAVID网站进行GO富集分析和KEGG通路分析。再应用AutoDock Vina将Degree排名前三与牛膝成分进行分子对接。通过对接打分选取部分结合力较强的靶基因,利用Pymol软件进行可视化。结果基于数据库筛选牛膝潜在活性化合物有8个,去除重复项后药物靶点共计212个。包括IL6、TNF、IL1B、PTGS2、VEGFA、CXCL8蛋白等。筛选数据库共计得到疾病靶点2 624个。而药物成分靶点与疾病靶点取交集得交集靶点共91个。通过KEGG富集分析得到97条与AS相关的通路。这些通路主要涉及三个方面：第一类是免疫系统的调控,包括Toll样受体信号通路、NF-KB信号通路、NOD样受体信号通路等;第二类是炎症反应的调节,例如脂肪因子通路和AK/STAT通路;第三类是骨代谢的调控,如Wnt/β- catenin信号通路、TNF通路以及破骨细胞分化过程。结论牛膝可能在免疫炎症、骨代谢相关通路来治疗AS,实现多成分、多靶点、多通路发挥对AS的治疗作用,具有一定的临床应用价值。

关键词: 牛膝, 强直性脊柱炎, 网络药理学, 作用机制

Abstract: Objective To investigate the mechanism of action of hyssop alone in the treatment of ankylosing spondylitis (AS) on the basis of network pharmacology. Methods The chemical composition of hyssop was searched using TCMSP, a technical platform for systematic pharmacology of traditional Chinese medicine, and the active ingredient targets of hyssop were searched using Swiss Target Prediction database, and then the GeneCards database, Drugbank database and Disgenet database were used to collect AS-related targets, so as to map AS-related targets The GeneCards database, Drugbank database and Disgenet database were then used to collect AS-related targets, thus mapping the AS-related targets and the predicted targets of hyssop, and finally obtaining the predicted targets of hyssop for AS. Potential targets for drug components to treat the disease were obtained with the help of Venny 2.1. Cyto-scape software was used to generate a protein-protein interaction (PPI) network for AS treatment with bullseye. GO and KEGG pathway analysis was performed using the DAVID website, followed by molecular docking via AutoDock Vina. Finally some of the stronger binding results were selected for visualization using Pymol software. Results There were 8 potentially active compounds of Oxalis based on database screening, with a total of 212 drug targets after removing duplicate terms. These included IL6, TNF, IL1B, PTGS2, VEGFA, CXCL8 protein, etc. A total of 2 624 disease targets were obtained from the screening database. The drug component targets and disease targets were intersected to obtain a total of 91 intersecting targets. The KEGG pathway analysis yielded 97 relevant pathways, and combined with previous literature studies, 12 possible pathways were screened for the treatment of AS, mainly divided into the following 4 categories: ① immune-related pathways: Toll-like receptor signalling pathway, NF-kB, NOD-like receptor signalling pathway, intestinal immune pathway, T-cell receptor signalling pathway;② inflammation-related pathways: adipokine pathway, AK/ST pathway;③ bone metabolism-related pathways: adipokine pathway, AK/ST pathway, etc. STAT pathway; (iii) bone metabolism-related pathways: Wnt/β-catenin signaling pathway, TNF pathway, osteoclast differentiation, steroid hormone synthesis; (iv) delayed fibrosis-related pathways: HIF-1a pathway, HIF-2a pathway. Conclusion Oxalis knee may play a role in immune-related pathways, inflammation-related pathways, bone metabolism-related pathways, and delayed fibrosis-related pathways through multi-target and multi-pathway treatment of AS.

Key words: Cow knee, Ankylosing spondylitis, Network pharmacology, Mechanism of action

中图分类号:

倪角角, 张浩, 陈平, 王海东, 王爱华. 基于网络药理学分析及分子对接技术探讨牛膝单药防治强直性脊柱炎的作用机制[J]. 中华养生保健, 2024, 42(18): 74-77.

NI Jiao-jiao, ZHANG Hao, CHEN Ping, WANG Hai-dong, WANG Ai-hua. Study on the Mechanism of Achyranthes Bidentata Single Drug in the Prevention and Treatment of Ankylosing Spondylitis Based on Network Pharmacological Analysis and Molecular Docking Technology[J]. ZHONGHUA YANGSHENG BAOJIAN, 2024, 42(18): 74-77.

参考文献

[1] 姜平,李念虎,魏传付,等.后路长节段经皮置钉内固定术治疗强直性脊柱炎并胸腰椎骨折的临床效果[J].中国脊柱脊髓杂志,2019,29(4):303-309.
[2] WARD M M, DEODHAR A, AKL E A, et al.American College of Rheumatology/SpondylitisAssociation of America/Spondyloarthritis Research and Treatment Network 2015 Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis[J]. Arthritis Rheumatol,2016,68(2):282-298.
[3] WANG Y, YI X D, LU H L.Influence of CYP2C9 and COX-2 genetic polymorphisms on clinical efficacy of non-steroidal anti-inflammatory drugs in treatment of ankylosing spondylitis[J]. Med Sci Monit,2017,23: 1775-1782.
[4] 翟佳羽,吕青,赵敏菁,等甲氨蝶呤和柳氮磺吡啶治疗强直性脊柱炎安全性和有效性的meta分析[J]中山大学学报(医学科学版),2015,36(1):42-54.
[5] 国家药典委员会.中华人民共和国药典:一部[S]北京:中国医药科技出版社,2015:38.
[6] 廖彭莹,王东,杨崇仁,等.苋科牛膝资源植物的化学成分研究进展[J]中草药, 2013,44(14):2019-2026.
[7] 吴珊珊,段振华,潘发明.强直性脊柱炎流行病学研究进展[J].安徽医科大学学报,2013,48(8):988-992.
[8] MACALUSO F, GUGGINO G, MAURO D, et al.Safety and efficacy of secukinumab treatment in a patient with ankylosing spondylitis and concomitant multiple sclerosis[J]. Clin Exp Rheumatol,2019,37(6):1096.
[9] MIGLIORE A, BIZZI E, BERNARDI M, et al.Indirect comparison be-tween subcutaneous biologic agents in ankylosing spondylitis[J]. Clin Drug Investig,2015,35(1):23-29.
[10] 黄永宾,胡培森.中医辨证治疗强直性脊柱炎[J].河南中医,2020,40(3):411-414.
[11] 刘美燕,刘维,杨会军.中药外治法治疗强直性脊柱炎的用药分析[J].中国实验方剂学杂志,2016,22(3):201-205.
[12] RAJENDRAN P, RENGARAJAN T, NANDAKUMAR N, et al.Kaempferol, a potential cytostatic and cure for inflammatory disorders[J]. Eur J Med Chem,2014,86:103-112.
[13] WONG S K, CHIN K Y, IMA-NIRWANA S.The osteoprotective effects of kaempferol: the evidence from in vivo and in vitro studies[J]. Drug Des Devel Ther,2019,13:3497-3514.
[14] DAMIANO F, GIANNOTTI L, GNONI G V, et al.Quercetin inhibition of SREBPs and ChREBP expression results in reduced cholesterol and fatty acid synthesis in C6 glioma cells[J]. Int J Biochem Cell Biol,2019,117:105618.
[15] DE OLIVEIRA M R, NABAVI S M, BRAIDY N, et al. Quercetin and the mitochondria: A mechanistic view[J]. Biotechnol Adv,2016,34(5):532-549.
[16] 肖嘉聪,麦嘉乐,张罡瑜,等.槲皮素调控关节炎软骨细胞胆固醇代谢的机制研究[J].中国骨质疏松杂志,2022,28(9):1336-1341.
[17] FAN L, QIU D, HUANG G, et al.Wogonin suppresses IL-10 production in B cells via STAT3 and ERK signaling pathway[J]. Journal of Immunology Research2020,2020:3032425.
[18] LI Y, ZENG C, TU M, et al.MicroRNA-200b acts as a tumor suppressor in osteosarcoma via targeting ZEB1[J]. Onco Targets Ther,2016,9:3101-3111.
[19] KILINC A A, ONAL P, OZTOSUN B, et al.Determination of tuberculin skin test for isoniazid prophylaxis in BCG vaccinated children who are using anti-TNF agents for rheumatologic diseases[J]. Pediatr Pulmonol,2020,55(10):2689-2696.
[20] KILINC A A, ONAL P, OZTOSUN B, et al.Radiologic parameters of ankylosing spondylitis patients treated with anti-TNF-α versus nonsteroidal anti-inflammatory drugs and sulfasalazine[J]. Eur Spine J,2019,28(4):649-657.
[21] 赵嘉英,赵阴环.强直性脊柱炎患者血浆IL-1水平变化[J].山东医药,2011, 51(2):85.
[22] LI D H, HE C R, LIU F P, et al.Annexin A2, up-regulated by IL-6, promotes the ossification of ligament fibroblasts from ankylosing spondylitis patients[J]. Biomed Pharmacother,2016,84:674-679.
[23] ZHANG Y, NING C, ZHOU H, et al.Interleukin-1β, interleukin-6, and interleukin-17A as indicators reflecting clinical response to celecoxib in ankylosing spondylitis patients[J]. Ir J Med Sci,2021,190(2):631-638.