Deciphering the Molecular Targets and Mechanisms of HGWD in the Treatment of Rheumatoid Arthritis Via Network Pharmacology and Molecular Docking

Overview

Journal Evid Based Complement Alternat Med

Specialty Rehabilitation Medicine

Date 2020 Sep 10

PMID 32908565

Citations 24

Authors

Wei Liu

Yihua Fan

Chunying Tian

Yue Jin

Shaopeng Du

Ping Zeng

Aihua Wang

Affiliations

Soon will be listed here.

Abstract

Background: Huangqi Guizhi Wuwu Decoction (HGWD) has been applied in the treatment of joint pain for more than 1000 years in China. Currently, most physicians use HGWD to treat rheumatoid arthritis (RA), and it has proved to have high efficacy. Therefore, it is necessary to explore the potential mechanism of action of HGWD in RA treatment based on network pharmacology and molecular docking methods.

Methods: The active compounds of HGWD were collected, and their targets were identified from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and DrugBank database, respectively. The RA-related targets were retrieved by analyzing the differentially expressed genes between RA patients and healthy individuals. Subsequently, the compound-target network of HGWD was constructed and visualized through Cytoscape 3.8.0 software. Protein-protein interaction (PPI) network was constructed to explore the potential mechanisms of HGWD on RA using the plugin BisoGenet of Cytoscape 3.8.0 software. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed in R software (Bioconductor, clusterProfiler). Afterward, molecular docking was used to analyze the binding force of the top 10 active compounds with target proteins of VCAM1, CTNNB1, and JUN.

Results: Cumulatively, 790 active compounds and 1006 targets of HGWD were identified. A total of 4570 differentially expressed genes of RA with a value <0.05 and |log 2(fold change)| > 0.5 were collected. Moreover, 739 GO entries of HGWD on RA were identified, and 79 pathways were screened based on GO and KEGG analysis. The core target gene of HGWD in RA treatment was JUN. Other key target genes included FOS, CCND1, IL6, E2F2, and ICAM1. It was confirmed that the TNF signaling pathway and IL-17 signaling pathway are important pathways of HGWD in the treatment of RA. The molecular docking results revealed that the top 10 active compounds of HGWD had a strong binding to the target proteins of VCAM1, CTNNB1, and JUN.

Conclusion: HGWD has important active compounds such as quercetin, kaempferol, and beta-sitosterol, which exert its therapeutic effect on multiple targets and multiple pathways.

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References

Bartok B, Firestein G . Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis. Immunol Rev. 2010; 233(1):233-55. PMC: 2913689. DOI: 10.1111/j.0105-2896.2009.00859.x. View

Tang Y, Li M, Wang J, Pan Y, Wu F . CytoNCA: a cytoscape plugin for centrality analysis and evaluation of protein interaction networks. Biosystems. 2014; 127:67-72. DOI: 10.1016/j.biosystems.2014.11.005. View

Fujii K, Tanaka Y, Hubscher S, Saito K, Ota T, Eto S . Cross-linking of CD44 on rheumatoid synovial cells up-regulates VCAM-1. J Immunol. 1999; 162(4):2391-8. View

Shannon P, Markiel A, Ozier O, Baliga N, Wang J, Ramage D . Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003; 13(11):2498-504. PMC: 403769. DOI: 10.1101/gr.1239303. View

Tanel A, Fonseca S, Yassine-Diab B, Bordi R, Zeidan J, Shi Y . Cellular and molecular mechanisms of memory T-cell survival. Expert Rev Vaccines. 2009; 8(3):299-312. PMC: 2680212. DOI: 10.1586/14760584.8.3.299. View

Wagner E, Nebreda A . Signal integration by JNK and p38 MAPK pathways in cancer development. Nat Rev Cancer. 2009; 9(8):537-49. DOI: 10.1038/nrc2694. View

Tsai M, Wang Y, Lai Y, Tsou H, Liou G, Ko J . Kaempferol protects against propacetamol-induced acute liver injury through CYP2E1 inactivation, UGT1A1 activation, and attenuation of oxidative stress, inflammation and apoptosis in mice. Toxicol Lett. 2018; 290:97-109. DOI: 10.1016/j.toxlet.2018.03.024. View

Fischer J, Hueber A, Wilson S, Galm M, Baum W, Kitson C . Combined inhibition of tumor necrosis factor α and interleukin-17 as a therapeutic opportunity in rheumatoid arthritis: development and characterization of a novel bispecific antibody. Arthritis Rheumatol. 2014; 67(1):51-62. DOI: 10.1002/art.38896. View

Li Y, Yao J, Han C, Yang J, Chaudhry M, Wang S . Quercetin, Inflammation and Immunity. Nutrients. 2016; 8(3):167. PMC: 4808895. DOI: 10.3390/nu8030167. View

10.

Gabriel S, Crowson C, OFallon W . The epidemiology of rheumatoid arthritis in Rochester, Minnesota, 1955-1985. Arthritis Rheum. 1999; 42(3):415-20. DOI: 10.1002/1529-0131(199904)42:3<415::AID-ANR4>3.0.CO;2-Z. View

11.

Lu W, Li L, Shen Y, Zhou R, Yang R, Pang X . [Network pharmacology study of Xiaoxuming Decoction based on vasodilatory and vasoconstrictory related GPCR targets]. Zhongguo Zhong Yao Za Zhi. 2019; 43(23):4698-4708. DOI: 10.19540/j.cnki.cjcmm.20181009.004. View

12.

Kong D, Kim Y, Kim M, Jang J, Lee S . Emerging Roles of Vascular Cell Adhesion Molecule-1 (VCAM-1) in Immunological Disorders and Cancer. Int J Mol Sci. 2018; 19(4). PMC: 5979609. DOI: 10.3390/ijms19041057. View

13.

Xu X, Zhang W, Huang C, Li Y, Yu H, Wang Y . A novel chemometric method for the prediction of human oral bioavailability. Int J Mol Sci. 2012; 13(6):6964-6982. PMC: 3397506. DOI: 10.3390/ijms13066964. View

14.

Schminke B, Trautmann S, Mai B, Miosge N, Blaschke S . Interleukin 17 inhibits progenitor cells in rheumatoid arthritis cartilage. Eur J Immunol. 2015; 46(2):440-5. PMC: 5064647. DOI: 10.1002/eji.201545910. View

15.

You J, Li C, Chen W, Wu X, Huang L, Li R . A network pharmacology-based study on Alzheimer disease prevention and treatment of Qiong Yu Gao. BioData Min. 2020; 13:2. PMC: 7183652. DOI: 10.1186/s13040-020-00212-z. View

16.

Xu M, Shi J, Min Z, Zhu H, Sun W . A Network Pharmacology Approach to Uncover the Molecular Mechanisms of Herbal Formula Kang-Bai-Ling for Treatment of Vitiligo. Evid Based Complement Alternat Med. 2019; 2019:3053458. PMC: 6875403. DOI: 10.1155/2019/3053458. View

17.

Wang W, Liu T, Yang L, Ma Y, Dou F, Shi L . Study on the multi-targets mechanism of triphala on cardio-cerebral vascular diseases based on network pharmacology. Biomed Pharmacother. 2019; 116:108994. DOI: 10.1016/j.biopha.2019.108994. View

18.

Jiang Y, Liu N, Zhu S, Hu X, Chang D, Liu J . Elucidation of the Mechanisms and Molecular Targets of Yiqi Shexue Formula for Treatment of Primary Immune Thrombocytopenia Based on Network Pharmacology. Front Pharmacol. 2019; 10:1136. PMC: 6780007. DOI: 10.3389/fphar.2019.01136. View

19.

Romao V, Lima A, Bernardes M, Canhao H, Fonseca J . Three decades of low-dose methotrexate in rheumatoid arthritis: can we predict toxicity?. Immunol Res. 2014; 60(2-3):289-310. DOI: 10.1007/s12026-014-8564-6. View

20.

Cross M, Smith E, Hoy D, Carmona L, Wolfe F, Vos T . The global burden of rheumatoid arthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 2014; 73(7):1316-22. DOI: 10.1136/annrheumdis-2013-204627. View