Network Pharmacology and Experimental Validation Explore the Pharmacological Mechanisms of Herb Pair for Treating Rheumatoid Arthritis

Comb Chem High Throughput Screen. 2024;27(12):1808-1822. doi: 10.2174/0113862073263839231129163200.

Abstract

Objective: This study aimed to elucidate the multitarget mechanism of the Mori Ramulus - Taxilli Herba (MT) herb pair in treating rheumatoid arthritis (RA).

Methods: The targets of the herb pair and RA were predicted from databases and screened through cross-analysis. The core targets were obtained using protein-protein interaction (PPI) network analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Finally, animal experiments were conducted to validate the anti-RA effect and mechanism of this herb pair.

Results: This approach successfully identified 9 active compounds of MT that interacted with 6 core targets (AKT1, TNF, IL6, TP53, VEGFA, and IL1β). Pathway and functional enrichment analyses revealed that MT had significant effects on the TNF and IL-17 signaling pathways. The consistency of interactions between active components and targets in these pathways was confirmed through molecular docking. Moreover, the potential therapeutic effect of MT was verified in vivo, demonstrating its ability to effectively relieve inflammation by regulating these targeted genes and pathways.

Conclusion: The present work suggests that the therapeutic effect of MT herb pair on RA may be attributed to its ability to regulate the TNF signaling pathway and IL-17 signaling pathway.

Keywords: IL-17 signaling pathway; TNF signaling pathway.; Traditional chinese medicine; herb pair; molecular docking; network pharmacology; rheumatoid arthritis.

MeSH terms

  • Animals
  • Antirheumatic Agents / chemistry
  • Antirheumatic Agents / pharmacology
  • Arthritis, Rheumatoid* / drug therapy
  • Arthritis, Rheumatoid* / metabolism
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / pharmacology
  • Humans
  • Mice
  • Molecular Docking Simulation*
  • Network Pharmacology*
  • Protein Interaction Maps / drug effects
  • Signal Transduction / drug effects

Substances

  • Drugs, Chinese Herbal
  • Antirheumatic Agents