S-allylcysteine inhibits chondrocyte inflammation to reduce human osteoarthritis via targeting RAGE, TLR4, JNK, and Nrf2 signaling: comparison with colchicine

Elmazoglu Z., AYDIN BEK Z. , Saribas S. G. , Ozogul C., GÖKER B. , Bitik B., ...More

BIOCHEMISTRY AND CELL BIOLOGY, vol.99, no.5, pp.645-654, 2021 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 99 Issue: 5
  • Publication Date: 2021
  • Doi Number: 10.1139/bcb-2021-0004
  • Page Numbers: pp.645-654
  • Keywords: osteoarthritis, chondrocytes, S-allylcysteine, colchicine, toll-like receptor-4, redox signaling, inflammation, nuclear factor erythroid 2-related factor 2, oxidative stress, ENDOPLASMIC-RETICULUM STRESS, INDUCED NEURONAL DEATH, KNEE OSTEOARTHRITIS, LIPID-PEROXIDATION, CARTILAGE, MATRIX, PHOSPHORYLATION, DEGRADATION, MANAGEMENT, CYSTEINE


The discovery of new pharmacological agents is needed to control the progression of osteoarthritis (OA), characterized by joint cartilage damage. Human OA chondrocyte (OAC) cultures were either applied to S-allylcysteine (SAC), a sulfur-containing amino acid derivative, or colchicine, an ancient anti-inflammatory therapeutic, for 24 h. SAC or colchicine did not change viability at 1 nM-10 mu M but inhibited p-JNK/pan-JNK. While SAC seems to be more effective, both agents inhibited reactive oxygen species (ROS), 3-nitrotyrosine (3-NT), lipid hydroperoxides (LPO), advanced lipoxidation end-products (ALEs as 4-hydroxy-2-nonenal, HNE), advanced glycation end-products (AGEs), and increased glutathione peroxidase (GPx) and type-II-collagen (COL2). IL-1 beta, IL-6, and osteopontin (OPN) were more strongly inhibited by SAC than by colchicine. In contrast, TNF-alpha was inhibited only by SAC, and COX2 was only inhibited by colchicine. Casp-1/ICE, GM-CSF, receptor for advanced glycation end-products (RAGE), and toll-like receptors (TLR4) were inhibited by both agents, but bone morphogenetic protein 7 (BMP7) was partially inhibited by SAC and induced by colchicine. Nuclear factor erythroid 2-related factor 2 (Nrf2) was induced by SAC; in contrast, it was inhibited by colchicine. Although they exert opposite effects on TNF-alpha, COX2, BMP7, andNrf2, SAC and colchicine exhibit anti-osteoarthritic properties in OAC by modulating redox-sensitive inflammatory signaling.