Pro-apoptotic and anti-inflammatory effects of araloside A on human rheumatoid arthritis fibroblast-like synoviocytes

Chem Biol Interact. 2019 Jun 1:306:131-137. doi: 10.1016/j.cbi.2019.04.025. Epub 2019 Apr 18.

Abstract

Rheumatoid arthritis fibroblast-like synoviocytes play an essential role in the occurrence and progression of rheumatoid arthritis. As the main pharmacologically active components of Aralia taibaiensis, total saponins, particularly triterpenoid saponins, have been shown to possess multiple pharmacological activities including relieving rheumatism. However, the effect of araloside A, a triterpenoid saponin extracted from the root bark of Aralia taibaiensis, on rheumatoid arthritis remains unknown. Cell counting kit-8 assay was employed to determine cell viability. Flow cytometry analysis, caspase-3/7 activity assay and Western blot analysis of cytochrome c and B-cell lymphoma 2 were conducted to evaluate cell apoptosis. Inflammation was assessed by detecting the production of inflammatory cytokines including interleukin-6 and interleukin-8, as well as inflammatory mediators including nitric oxide and prostaglandin E2. The changes of the nuclear factor kappa B pathway were examined by Western blot. Results showed that araloside A concentration-dependently inhibited the proliferation of MH7A cells. Meanwhile, araloside A dose-dependently augmented the apoptotic rate and caspase-3/7 activity, increased cytochrome c level and decreased B-cell lymphoma 2 level in MH7A cells. Araloside A concentration-dependently curbed the production of interleukin-6, interleukin-8, prostaglandin E2 and nitric oxide in MH7A cells. In addition, we found that araloside A inhibited the nuclear factor kappa B pathway and inhibition of the nuclear factor kappa B pathway by BAY11-7082 and PDTC showed a similar role to araloside A in MH7A cells. Taken together, araloside A exerted pro-apoptotic and anti-inflammatory effects in rheumatoid arthritis fibroblast-like synoviocytes via inhibition of the nuclear factor kappa B pathway.

Keywords: Apoptosis; Araloside A; Inflammation; NF-κB pathway; Rheumatoid arthritis fibroblast-like synoviocytes.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / pathology*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Fibroblasts
  • Humans
  • Molecular Conformation
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / chemistry
  • Oleanolic Acid / pharmacology
  • Saponins / chemistry
  • Saponins / pharmacology*
  • Structure-Activity Relationship
  • Synoviocytes / drug effects*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Saponins
  • Oleanolic Acid
  • araloside A