Journal of Shandong University (Health Sciences) ›› 2022, Vol. 60 ›› Issue (3): 29-38.doi: 10.6040/j.issn.1671-7554.0.2021.0656

Previous Articles    

Exploration of Huangqi Guizhi Wuwutang in the treatment of ankylosing spondylitis based on network pharmacology

LI Mingbo1, HUANG Yanbo1, LIU Juncheng1, REN Dongcheng2, TAN Chengshuang3, XU Jixi4, DING Jinyong4   

  1. 1. The First Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Guangzhou 510405, Guangdong, China;
    2. Department of Orthopedics, The Third Peoples Hospital of Shenzhen, Shenzhen 518112, Guangdong, China;
    3. Department of Orthopedics, The Second Peoples Hospital of Panyu District, Guangzhou 511400, Guangdong, China;
    4. Department of Spine Orthopedic, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong, China
  • Published:2022-03-09

PDF (PC)

89

Abstract: Objective To investigate the molecular mechanism of Huangqi Guizhi Wuwutang in the treatment of ankylosing spondylitis(AS)by using network pharmacology and molecular docking technology. Methods The chemical components and targets of Huangqi Guizhi Wuwutang were searched in TCMSP database, and gene annotation of drug targets were carried out. AS disease-related targets were searched from Gene Cards, OMIM, PharmGkb, TTD, and DrugBank database. Then, a visual network of “traditional Chinese medicine-components-intersection target” was constructed by using Cytoscape 3.8.0 software among drugs, active chemical components and intersection target. The visual network result data were imported into the String database to construct the protein interaction network. R language software and R package were used to analyze GO and KEGG enrichment. Finally, molecular docking was conducted between the core active component and the core target. Results A total of 74 active compounds of Huangqi Guizhi Wuwutang were obtained. After the reverse screening of active ingredients of TCM decoction according to the common targets of diseases and TCM decoction, 32 active ingredients were reserved, and 997 corresponding targets were predicted. A total of 2,234 AS related targets and 78 genes were intersected. Eight core targets were selected after the second scoring using CytoNCA plug-in R software. A total of 1,990 and 135 enrichment terms were acquired by GO and KEGG enrichment analyses, respectively. The results of molecular docking showed that the target of the active component and the target of the core gene could be docked stably. Conclusion In the treatment of AS, Huangqi Guizhi Wuwutang acts on PTGS2, IL6, TNF, VEGFA, IL1B, ICAM1, STAT1, CXCL8 and other gene targets through quercetin, paeoniflorin, kaempferol and other components. Thus, it can affect the function of “lipid and atherosclerosis” “AGE-RAGE signaling pathway” “IL-17 signaling pathway” “TNF signaling pathway” “NF-kappa B signaling pathway” and other related pathways.

Key words: Ankylosing spondylitis, Huangqi Guizhi Wuwutang, Blood paralysis, Network pharmacology, Molecular docking

CLC Number: 

  • R681.5
[1] Voruganti A, Bowness P. New developments in our understanding of ankylosing spondylitis pathogenesis[J]. Immunology, 2020, 161(2): 94-102.
[2] Daikh DI, Chen PP. Advances in managing ankylosing spondylitis[J]. F1000Prime Rep, 2014, 6: 78. doi: 10.12703/P6-78.
[3] Hanson A, Brown MA. Genetics and the causes of ankylosing spondylitis[J]. Rheum Dis Clin North Am, 2017, 43(3): 401-414.
[4] Berg IJ, Semb AG, van der Heijde D, et al. CRP and ASDAS are associated with future elevated arterial stiffness, a risk marker of cardiovascular disease, in patients with ankylosing spondylitis: results after 5-year follow-up[J]. Ann Rheum Dis, 2015, 74(8): 1562-1566.
[5] Reveille JD, Witter JP, Weisman MH. Prevalence of axial spondylarthritis in the United States: estimates from a cross-sectional survey[J]. Arthritis Care Res(Hoboken), 2012, 64(6): 905-910.
[6] Taurog JD, Chhabra A, Colbert RA. Ankylosing spondylitis and axial spondyloarthritis[J]. N Engl J Med, 2016, 374(26): 2563-2574.
[7] Blair HA. Secukinumab: a review in ankylosing spondylitis [J]. Drugs, 2019, 79(4): 433-443.
[8] 李满意,娄玉钤.骨痹的源流及相关历史文献复习[J].风湿病与关节炎, 2014, 3(12): 59-68.
[9] 李满意,刘红艳,陈传榜,等.骨痹的证治[J].风湿病与关节炎, 2020, 9(12): 53-56.
[10] 雷艳,王新昌.黄芪桂枝五物汤在风湿病中的临床应用[J].黑龙江中医药, 2014(6): 39-41. doi: CNKI:SUN:HLZY.0.2014-06-028.
[11] 时文才,聂晨旭,胡晓龙,等.黄芪桂枝五物汤合血府逐瘀汤联合针灸治疗早期强直性脊柱炎临床研究[J].陕西中医, 2020, 41(3): 315-317.
[12] 彭智平,周强.仝小林辨治强直性脊柱炎经验[J].河南中医, 2013, 33(7): 1040-1041.
[13] 黄仰模,黄奕蕾,刘丽娟,等. 运用金匮要略方治疗强直性脊柱炎的体会[A]. 中国中西医结合学会风湿病专业委员会.全国第十二届中西医结合风湿病学术会议论文汇编[C].北京:中国中西医结合学会, 2014: 3.
[14] 李鑫,曹建中,满荣勇,等.黄芪桂枝五物汤治疗类风湿关节炎的研究进展[J].中国实验方剂学杂志, 2021, 27(6): 176-181. LI Xin, CAO Jianzhong, MAN Rongyong, et al. Research progress of rheumatoid arthritis with Huangqi Guizhi Wuwutang[J]. Chinese Journal of Experimental Traditional Medical Formulae, 2021, 27(6): 176-181.
[15] Granato M, Rizzello C, Gilardini Montani MS, et al. Quercetin induces apoptosis and autophagy in primary effusion lymphoma cells by inhibiting PI3K/AKT/mTOR and STAT3 signaling pathways[J]. J Nutr Biochem, 2017, 41: 124-136. doi: 10.1016/j.jnutbio.2016.12.011.
[16] 于维汉,何耀华.槲皮素在治疗骨关节炎中作用机制的研究进展[J].中华骨与关节外科杂志, 2019, 12(6): 477-480. YU Weihan, HE Yaohua. Advance in the mechanism of quercetin in the treatment of osteoarthritis[J]. Chinese Journal of Bone and Joint Surgery, 2019, 12(6): 477-480.
[17] 裘世杰,罗淦,汤样华,等.芍药苷及芍药苷-6-氧-苯磺酸酯在骨伤科疾病中的应用进展[J].中国中医药科技, 2021, 28(5): 864-867.
[18] 雷晓青,陈鳌,刘毅,等.山萘酚药理作用的研究进展[J].微量元素与健康研究, 2017, 34(2): 61-62.
[19] Wong SK, Chin KY, 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. doi: 10.2147/DDDT.S227738.
[20] Song IH, Poddubnyy D. New treatment targets in ankylosing spondylitis and other spondyloarthritides [J]. Curr Opin Rheumatol, 2011, 23(4): 346-351.
[21] 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.
[22] Li DH, He CR, Liu FP, 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. doi: 10.1016/j.biopha.2016.09.091.
[23] Ma S, Wang DD, Ma CY, et al. microRNA-96 promotes osteoblast differentiation and bone formation in ankylosing spondylitis mice through activating the Wnt signaling pathway by binding to SOST[J]. J Cell Biochem, 2019, 120(9): 15429-15442.
[24] Bleil J, Maier R, Syrbe U, et al. In situ analysis of interleukin-6 expression at different sites of zygapophyseal joints from patients with ankylosing spondylitis in comparison to controls[J]. Scand J Rheumatol, 2015, 44(4): 296-301.
[25] Coksevim NH, Durmus D, Kuru O. Effects of global postural reeducation exercise and anti-TNF treatments on disease activity, function, fatigue, mobility, sleep quality and depression in patients with active Ankylosing spondylitis: a prospective follow-up study[J]. J Back Musculoskelet Rehabil, 2018, 31(6): 1005-1012.
[26] Atzeni F, Nucera V, Galloway J, et al. Cardiovascular risk in ankylosing spondylitis and the effect of anti-TNF drugs: a narrative review[J]. Expert Opin Biol Ther, 2020, 20(5): 517-524.
[27] Molnar C, Scherer A, Baraliakos X, et al. TNF blockers inhibit spinal radiographic progression in ankylosing spondylitis by reducing disease activity: results from the Swiss Clinical Quality Management cohort[J]. Ann Rheum Dis, 2018, 77(1): 63-69.
[28] Son SM, Choi SH, Shin JK, 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.
[29] Kucuk A, Ugur Uslu A, Icli A, et al. The LDL/HDL ratio and atherosclerosis in ankylosing spondylitis [J]. Z Rheumatol, 2017, 76(1): 58-63.
[30] Fotoh DS, Serag DM, Badr IT, et al. Prevalence of subclinical carotid atherosclerosis and vitamin D deficiency in Egyptian ankylosing spondylitis patients[J]. Arch Rheumatol, 2020, 35(3): 335-342.
[31] Stanek A, Cholewka A, Wielkoszyński T, et al. Increased levels of oxidative stress markers, soluble CD40 ligand, and carotid intima-media thickness reflect acceleration of atherosclerosis in male patients with ankylosing spondylitis in active phase and without the classical cardiovascular risk factors[J]. Oxid Med Cell Longev, 2017, 2017: 9712536. doi: 10.1155/2017/9712536.
[32] Stanek A, Cholewka A, Wielkoszyński T, et al. Whole-body cryotherapy decreases the levels of inflammatory, oxidative stress, and atherosclerosis plaque aarkers in male patients with active-phase ankylosing spondylitis in the absence of classical cardiovascular risk factors[J]. Mediators Inflamm, 2018, 2018: 8592532. doi: 10.1155/2018/8592532.
[33] Zardi EM, Pipita ME, Giorgi C, et al. Differences in carotid atherosclerosis between patients with ankylosing spondylitis treated with tumor necrosis factor-α antagonists and healthy matched controls[J]. Medicine(Baltimore), 2018, 97(27): e11250.
[34] Pusztai A, Hamar A, Horváth á, et al. Soluble vascular biomarkers in rheumatoid arthritis and ankylosing spondylitis: effects of 1-year antitumor necrosis factor-α therapy [J]. J Rheumatol, 2020, 48(6): 821-828.
[35] 裴超,邵霖霖,刘晶,等.基于网络药理学与分子对接技术探讨红花治疗视网膜静脉阻塞的作用机制研究[J].天然产物研究与开发, 2020, 32(11): 1844-1851, 1865. PEI Chao, SHAO Linlin, LIU Jing, et al. Study on the mechanism of Carthami Flos in treating retinal vein occlusion based on network pharmacology and molecular docking technology[J]. Natural Product Research and Development, 2020, 32(11): 1844-1851, 1865.
[1] YU Ying, ZHANG Gong, LIU Jing, YAN Shitong, HAN Tao, HUANG Hailiang. Potential mechanism of Astragalus membranaceus in the prevention of COVID-19 based on network pharmacology and molecular docking [J]. Journal of Shandong University (Health Sciences), 2021, 59(4): 6-16.
[2] WANG Liya, MA Zhenzhen, YANG Qingrui. Association between PTGER4 gene polymorphism and susceptibility of ankylosing spondylitis in Han population in Shandong Province [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(6): 31-34.
[3] ZHANG Peiyi, ZHOU Shufen, WANG Meiying, LEI Zhenhua, WENG Junxiong, TIAN Ye, PENG Xin, FU Biling, DENG Liuxia, ZOU Shihai, GUO Chengshan. Expression of chemokine CXCL16 and its receptor CXCR6 can be suppressed by rcombinant human TNF receptor α Ⅱ-Ig fusion protein in ankylosing spondylitis [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(12): 51-56.
[4] XIA Yu1， WANG Lai-cheng1， SUN Hui1， TANG Hong-wei2， MA Chun-yan1， CUI Bin1， ZHAO Yue-ran1. Association of polymorphisms in the ERAP1 gene with ankylosing spondylitis in the Han Chinese population [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2011, 49(10): 127-130.
[5] LIU Wen-guang,WANG Shao-jin,WANG Xing-shan,DUAN Yuan-tao,LIU Sheng-hou. Effect of total hip arthroplasty in ankylosing spondylitis with tetanic deformity of the hip [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2008, 46(2): 192-195.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd