S-allylcysteine inhibits chondrocyte inflammation to reduce human osteoarthritis via targeting RAGE, TLR4, JNK, and Nrf2 signaling: comparison with colchicine
Autor: | Zubeyir Elmazoglu, Cem Nuri Aktekin, Berna Goker, Zehra Aydın Bek, Candan Ozogul, Sanem Saribas, B. Bitik, Çimen Karasu |
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Rok vydání: | 2021 |
Předmět: |
chemistry.chemical_classification
Reactive oxygen species business.industry Inflammation Cell Biology Osteoarthritis Pharmacology medicine.disease medicine.disease_cause Biochemistry Chondrocyte RAGE (receptor) chemistry.chemical_compound medicine.anatomical_structure chemistry medicine TLR4 Colchicine medicine.symptom business Molecular Biology Oxidative stress |
Zdroj: | Biochemistry and Cell Biology. 99:645-654 |
ISSN: | 1208-6002 0829-8211 |
Popis: | 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 µM 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-1β, IL-6, and osteopontin (OPN) were more strongly inhibited by SAC than by colchicine. In contrast, TNF-α 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-α, COX2, BMP7, and Nrf2, SAC and colchicine exhibit anti-osteoarthritic properties in OAC by modulating redox-sensitive inflammatory signaling. |
Databáze: | OpenAIRE |
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