Formononetin inhibits IL-1β-induced inflammation in human chondrocytes and slows the progression of osteoarthritis in rat model via the regulation of PTEN/AKT/NF-κB pathway

Int Immunopharmacol. 2022 Dec;113(Pt A):109309. doi: 10.1016/j.intimp.2022.109309. Epub 2022 Oct 25.

Abstract

Background/aim: Osteoarthritis (OA) is a common degenerative disease characterized by cartilage degradation and inflammation. This study aimed to investigate the anti-inflammatory properties of formononetin, an isoflavone extracted from astragalus membranaceus, on OA.

Methods: Human OA chondrocytes were pretreated in vitro with formononetin and subsequently stimulated with IL-1β. The production of inflammatory mediators, cytokines and the synthesis of catabolic factors were evaluated by ELISA and Western blot analysis. In addition, a rat model of OA was established and treated with formononetin.

Results: Formononetin attenuated the overproduction of inflammatory mediators and cytokines, suppressed the expression of cyclooxygenase-2 and inducible nitric oxide synthase, and inhibited the synthesis of catabolic factors such as MMPs and thrombospondin motifs 5. Furthermore, formononetin exerted protective effects in a rat model of OA. Mechanistically, we found that formononetin inhibited IL-1β induced activation of nuclear factor kappa B and AKT by activating the phosphatase and tensin homolog.

Conclusions: Formononetin could be used as a potential agent for OA treatment.

Keywords: AKT; Formononetin; Inflammation; NF-κB; Osteoarthritis; PTEN.

MeSH terms

  • Animals
  • Cells, Cultured
  • Chondrocytes
  • Humans
  • Inflammation / metabolism
  • Inflammation Mediators / metabolism
  • Interleukin-1beta / metabolism
  • Isoflavones* / pharmacology
  • Isoflavones* / therapeutic use
  • NF-kappa B / metabolism
  • Osteoarthritis* / drug therapy
  • Osteoarthritis* / metabolism
  • PTEN Phosphohydrolase / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats

Substances

  • NF-kappa B
  • formononetin
  • Proto-Oncogene Proteins c-akt
  • Interleukin-1beta
  • Isoflavones
  • Inflammation Mediators
  • PTEN protein, human
  • PTEN Phosphohydrolase
  • Pten protein, rat