Sinensetin attenuates IL-1β-induced cartilage damage and ameliorates osteoarthritis by regulating SERPINA3

Food Funct. 2022 Oct 3;13(19):9973-9987. doi: 10.1039/d2fo01304e.

Abstract

Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degeneration, subchondral bone sclerosis, synovial hyperplasia and osteophyte formation as the main pathological manifestations. Age, mechanical stress and inflammation are the main factors that induce joint degeneration in the pathogenesis of OA. Sinensetin (SIN) is a natural flavonoid with anti-inflammatory and antioxidant properties. This study aims to investigate the effect of SIN on OA. We have investigated the anti-inflammatory and chondroprotective effects of SIN on IL-1β-induced human OA chondrocytes and a rat OA model. In vitro, human chondrocytes were induced by 5 ng mL-1 IL-1β and treated with different concentrations of SIN. The results suggest that SIN can inhibit IL-1β-induced overproduction of pro-inflammatory mediators in human OA chondrocytes, including COX2, iNOS, TNF-α and IL-6, and also reduce the production of MMP13 and MMP9, thus protecting the degradation of the extracellular matrix. In addition, SIN can inhibit the activation of NF-κB by regulating the expression of SERPINA3. In an in vivo experiment, rats were randomly divided into 3 groups, namely the sham operation group, OA model group and SIN group, and were given normal saline or 20 mg kg-1 SIN, respectively. The knee cartilage tissue was removed 6 weeks after surgery for analysis and detection, and our studies have shown that SIN can effectively delay the progression of OA in rats and protect cartilage. In conclusion, our study shows that SIN has good application potential in the treatment of OA.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Antioxidants / pharmacology
  • Cartilage, Articular*
  • Cells, Cultured
  • Cyclooxygenase 2 / metabolism
  • Flavonoids / pharmacology
  • Humans
  • Inflammation Mediators / pharmacology
  • Interleukin-6
  • Matrix Metalloproteinase 13 / genetics
  • Matrix Metalloproteinase 13 / metabolism
  • Matrix Metalloproteinase 9
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Osteoarthritis* / drug therapy
  • Osteoarthritis* / genetics
  • Osteoarthritis* / metabolism
  • Rats
  • Saline Solution / pharmacology
  • Saline Solution / therapeutic use
  • Serpins
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Flavonoids
  • Inflammation Mediators
  • Interleukin-6
  • NF-kappa B
  • SERPINA3 protein, human
  • Saline Solution
  • Serpins
  • Tumor Necrosis Factor-alpha
  • sinensetin
  • Cyclooxygenase 2
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 9