A synergistic effect of triptolide and curcumin on rheumatoid arthritis by improving cell proliferation and inducing cell apoptosis via inhibition of the IL-17/NF-κB signaling pathway

Int Immunopharmacol. 2024 Dec 5;142(Pt A):112953. doi: 10.1016/j.intimp.2024.112953. Epub 2024 Sep 2.

Abstract

Rheumatoid arthritis (RA) is a chronic, progressive, systemic autoimmune disease. While triptolide (TPL) and curcumin (CUR) are known to have multiple beneficial effects on RA, the combined effect of TPL and CUR remains unexplored. This study aimed to investigate their synergistic effect on cell proliferation and apoptosis via the IL-17/NF-κB signaling pathway. The collagen-induced arthritis (CIA) rat model was established, showing severe joint and synovial damage compared to normal rats. Treatment with TPL and CUR reduced the severity of RA in the CIA rat model and alleviated serum inflammatory cytokines, such as rheumatoid factor, IL-17, TNF-α, IL-1β, and IL-6. The elevated levels of IL-17 and NF-κB in CIA rats were also inhibited, and the resistant apoptosis was aggravated by TPL and CUR. In vitro, the improvement of cell proliferation and induction of apoptosis were observed in LPS-stimulated MH7A cells treated with TPL and CUR, associated with the inhibition of the IL-17/NF-κB signaling pathway. Taken together, a synergistic effect of TPL and CUR on RA may involve relieving symptoms, improving excessive proliferation, inducing apoptosis resistance, and inhibiting the IL-17/NF-κB signaling pathway.

Keywords: Apoptosis; Cell proliferation; Curcumin; IL-17/NF-κB Signaling Pathway; Rheumatoid Arthritis; Triptolide.

MeSH terms

  • Animals
  • Apoptosis* / drug effects
  • Arthritis, Experimental* / drug therapy
  • Arthritis, Experimental* / pathology
  • Arthritis, Rheumatoid* / drug therapy
  • Arthritis, Rheumatoid* / pathology
  • Cell Line
  • Cell Proliferation* / drug effects
  • Curcumin* / pharmacology
  • Curcumin* / therapeutic use
  • Diterpenes* / pharmacology
  • Diterpenes* / therapeutic use
  • Drug Synergism*
  • Epoxy Compounds* / pharmacology
  • Epoxy Compounds* / therapeutic use
  • Humans
  • Interleukin-17* / metabolism
  • Male
  • Mice
  • NF-kappa B* / metabolism
  • Phenanthrenes* / pharmacology
  • Phenanthrenes* / therapeutic use
  • Rats
  • Signal Transduction* / drug effects

Substances

  • triptolide
  • Diterpenes
  • Phenanthrenes
  • Epoxy Compounds
  • Curcumin
  • NF-kappa B
  • Interleukin-17