Natural ingredients-derived antioxidants attenuate H2O2-induced oxidative stress and have chondroprotective effects on human osteoarthritic chondrocytes via Keap1/Nrf2 pathway

Free Radic Biol Med. 2020 May 20:152:854-864. doi: 10.1016/j.freeradbiomed.2020.01.185. Epub 2020 Jan 31.

Abstract

Osteoarthritis (OA) is the most common disabling joint disease and its pathological process is closely related to oxidative stress. Recent studies have shown that antioxidants allicin, sulforaphane, and lycopene derived from natural ingredients garlic, broccoli, and tomato can reduce the degree of oxidative stress and the expression of inflammatory markers, indicating that theses antioxidants might be helpful for OA treatment. In this study, we investigated the effects of allicin, sulforaphane, and lycopene on H2O2-stimulated human osteochondral samples and osteoarthritic chondrocytes. Our results revealed that allicin, sulforaphane, and lycopene effectively reduced the oxidative stress-induced cell apoptosis, and increased gene expression of antioxidant enzymes. Besides, these natural ingredients-derived antioxidants reduced the expression of inflammatory factors, enhanced the chondrogenic matrix synthesis, and reduced the hypertrophic differentiation of osteoarthritic chondrocytes. These regulations were mainly through the activation of Keap1/Nrf2 pathway. Our findings suggest that these antioxidants might be a potential therapeutic strategy for OA.

Keywords: Antioxidants; Keap1/Nrf2; Osteoarthritis; Oxidative stress.

MeSH terms

  • Antioxidants* / pharmacology
  • Chondrocytes / metabolism
  • Humans
  • Hydrogen Peroxide / toxicity
  • Kelch-Like ECH-Associated Protein 1 / genetics
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • NF-E2-Related Factor 2* / genetics
  • NF-E2-Related Factor 2* / metabolism
  • Oxidative Stress

Substances

  • Antioxidants
  • KEAP1 protein, human
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • Hydrogen Peroxide