Drug Design, Development and Therapy (Dec 2023)

Integrated Network Pharmacology and Experimental Approach to Investigate the Protective Effect of Jin Gu Lian Capsule on Rheumatoid Arthritis by Inhibiting Inflammation via IL-17/NF-κB Pathway

  • Chen T,
  • Li S,
  • Lian D,
  • Hu Q,
  • Hou H,
  • Niu D,
  • Li H,
  • Song L,
  • Gao Y,
  • Chen Y,
  • Hu X,
  • Li J,
  • Ye Z,
  • Peng B,
  • Zhang G

Journal volume & issue
Vol. Volume 17
pp. 3723 – 3748

Abstract

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Tengfei Chen,1,* Sihan Li,1,* Dongyin Lian,1 Qin Hu,2 Hongping Hou,1 Delian Niu,1 Han Li,1 Ling Song,1 Yunhang Gao,1 Ying Chen,1 Xiaoru Hu,3 Jianrong Li,1 Zuguang Ye,1 Bo Peng,1 Guangping Zhang1 1Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2College of Life Sciences and Bio-Engineering, Beijing University of Technology, Beijing, People’s Republic of China; 3National Institute for Food and Drug Control, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bo Peng; Guangping Zhang, Tel +8610 64056575, Email [email protected]; [email protected]: This study aimed to investigate the main pharmacological action and underlying mechanisms of Jin Gu Lian Capsule (JGL) against rheumatoid arthritis (RA) based on network pharmacology and experimental verification.Methods: Network pharmacology approaches were performed to explore the core active compounds of JGL, key therapeutic targets, and signaling pathways. Molecular docking was used to predict the binding affinity of compounds with targets. In vivo experiments were undertaken to validate the findings from network analysis.Results: A total of 52 targets were identified as candidate JGL targets for RA. Sixteen ingredients were identified as the core active compounds, including, quercetin, myricetin, salidroside, etc. Interleukin-1 beta (IL1B), transcription factor AP-1 (JUN), growth-regulated alpha protein (CXCL1), C-X-C motif chemokine (CXCL)3, CXCL2, signal transducer and activator of transcription 1 (STAT1), prostaglandin G/H synthase 2 (PTGS2), matrix metalloproteinase (MMP)1, inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB) and transcription factor p65 (RELA) were obtained as the key therapeutic targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the efficacy of JGL was functionally involved in regulating immune-mediated inflammation, in which IL-17/NF-κB signaling was recommended as one of the main pathways. Molecular docking suggested that the core active compounds bound strongly to their respective targets. Experimentally, JGL treatment mitigated inflammation, showed analgesic activity, and ameliorated collagen-induced arthritis. Enzyme-linked immunosorbent assay showed that JGL effectively reduced the serum levels of cytokines, chemokines, and MMPs. Immunohistochemistry staining showed that JGL markedly reduced the expression of the targets in IL-17/NF-κB pathway including IL-17A, IL-17RA, NF-κB p65, C-X-C motif ligand 2, MMP1 and MMP13.Conclusion: This investigation provided evidence that JGL may alleviate RA symptoms by partially inhibiting the immune-mediated inflammation via IL-17/NF-κB pathway. Keywords: rheumatoid arthritis, Jin Gu Lian capsules, network pharmacology, experimental validation, immune-mediated inflammation

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