Mechanism investigation of Duhuo Jisheng pill against rheumatoid arthritis based on a strategy for the integration of network pharmacology, molecular docking and in vivo experimental verification.

CONTEXT: Duhuo Jisheng pill (DHJS) is a classic traditional Chinese medicine (TCM) formula for rheumatoid arthritis (RA). The effective components and therapeutic mechanisms of DHJS for treating RA are still unclear. OBJECTIVE: To explore the potential mechanism of DHJS against RA by means of network pharmacology and experimental verification. MATERIALS AND METHODS: A network pharmacology and molecular docking analysis based on phytochemistry was used to elucidate the mechanism of DHJS against RA. The targets of DHJS anti-RA active ingredient were obtained by searching TCMSP, ETCM and TCMSID. The RA model induced by collagen was established in Wistar rats. The rats in the DHJS group were administered doses of 0.5, 1.0 and 2.0 g/kg for a period of 10 d. The expression of targets was measured with Western blot. RESULTS: Network pharmacology analysis showed that the anti-RA effect of DHJS was mediated by targets involved in immunity, inflammation and apoptosis, as well as PI3K-Akt and NF-κB signalling pathways. Of 2.0 g/kg DHJS significantly alleviated the ankle inflammation (IL-6: 62.73 ± 8.39 pg/mL, IL-1ß: 50.49 ± 11.47 pg/mL, TNF-α: 16.88 ± 3.05 pg/mL, IL-17A: 12.55 ± 1.87 pg/mL, IL-10: 16.24 ± 3.00 pg/mL), comparing with the model group (IL-6: 92.02 ± 13.25 pg/mL, IL-1ß: 71.85 ± 4.12 pg/mL, TNF-α: 25.64 ± 3.69 pg/mL, IL-17A: 22.14 ± 4.56 pg/mL, IL-10: 9.51 ± 3.03 pg/mL) (p < 0.05). Moreover, the protein expression of p-PI3K, p-AKT and p-p65 significantly decreased after DHJS administration. CONCLUSIONS: DHJS could alleviate the collagen-induced arthritis (CIA) by the PI3K/AKT/NF-κB signalling pathway.

Recent advances on signaling pathways and their inhibitors in rheumatoid arthritis.

Rheumatoid arthritis (RA) is characterized by systemic synovitis leading to joint destruction in which imbalances in pro-inflammatory and anti-inflammatory cytokines promote the induction of autoimmunity. Some pro-inflammatory cytokines can trigger the signaling pathways which responsible for immune-mediated inflammation in RA, and the activated signaling pathways produce pro-inflammatory cytokines, resulting in aggravation of RA. Hence, understanding of the signaling pathways and their inhibitors might be advantageous in the development of therapeutic targets and new drugs for RA. In the current review, we summarize the signaling pathways involved in the pathogenesis of RA as well as the potential role of specific inhibitors in its management. We hope this paper may serve a reference for future studies on signaling pathways implicated in the pathogenesis of RA and benefit the treatment of RA.