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

Pharm Biol. 2023 Dec;61(1):1431-1445. doi: 10.1080/13880209.2023.2252854.

Abstract

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-1β: 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-1β: 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.

Keywords: PI3K/AKT/NF-κB pathway; Traditional Chinese medicine; bioinformation technology; molecular mechanism.

MeSH terms

  • Animals
  • Arthritis, Rheumatoid* / drug therapy
  • Inflammation
  • Interleukin-10
  • Interleukin-17
  • Interleukin-6
  • Molecular Docking Simulation
  • NF-kappa B*
  • Network Pharmacology
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Rats
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha

Substances

  • duhuo jisheng
  • NF-kappa B
  • Interleukin-10
  • Interleukin-17
  • Interleukin-6
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Tumor Necrosis Factor-alpha

Grants and funding

This study was supported by the Natural Science Foundation of Heilongjiang Province [No. YQ2019H005], the National Natural Science Foundation of China [No. 81903763], the China Postdoctoral Science Foundation [No. 2019M661312], the Fundamental Research Funds for the Provincial Universities [No.2018XN-25, JFWLD201904], the Nanjing medical science and technology development fund [No. YKK20179], the Initial Scientific Research Fund of the Talents Introduced in Nanjing Lishui People’s Hospital [No. 2021YJ01] and Guiding Science and Technology Plan Project of Daqing City [szd-2015-12].