Network Pharmacology and Experiments Reveal Kunxian Capsule's Anti-Inflammatory Mechanism via MAPK/Dopamine Pathways
Te Zheng, Kannan Maharajan, Huiwen Zhang, Ruijiao Ma, Qing Xia, Rostyslav Stoika, Yun ZhangIntroduction:
Kunxian capsule (KX) is a Traditional Chinese Medicine widely used for the treatment of rheumatoid arthritis (RA) and other inflammatory diseases. However, its anti-inflammatory mechanism was unclear.
Introduction:
Kunxian capsule (KX) is a Traditional Chinese Medicine widely used for the treatment of rheumatoid arthritis (RA) and other inflammatory diseases. However, its anti-inflammatory mechanism was unclear.
Methods:
A combination of network pharmacology, molecular docking, and a CuSO4-induced zebrafish inflammation model was used. RT-qPCR was performed to analyze gene expression related to inflammation and the MAPK/dopamine pathways.
Results:
Network pharmacology identified 122 intersecting targets between KX and RA, and KEGG enrichment analysis highlighted the MAPK and dopamine signaling pathways. KX alleviated inflammation in zebrafish and regulated the expression of inflammatory cytokines (cox2, ptges, il8, il1β, il6, inos, il10, tgf-β) and MAPK/dopamine pathway genes (nfκb2, ikbaα, mapk8b, mapk14a, gria2, drd1b, drd2, ppp3ca, ddc). Molecular docking demonstrated that four key components-triptolide, anhydroicaritin, epimedin B, and kaempferol-exhibited stable binding to core targets such as MAPK14 (binding energy: -8.35 kcal/mol), MAPK8 (-8.2 kcal/mol), COX2 (-8.34 kcal/mol), and DRD1B (-7.79 kcal/mol).
Discussion:
The study reflected the multi-component, multi-target nature of traditional Chinese medicine, and highlighted the potential of traditional Chinese medicine to treat inflammatory diseases through multiple signaling pathways.
Conclusion:
The present study confirmed that KX plays a therapeutic role in RA by inhibiting the inflammatory response through the MAPK/dopamine pathway in the zebrafish model.