Theobromine mitigates IL-1β-induced oxidative stress, inflammatory response, and degradation of type II collagen in human chondrocytes

• Published in: International immunopharmacology 2020-05, Vol.82, p.106226-106226, Article 106226
• Main Authors: Gu, Ronghe, Shi, Yu, Huang, Weiguo, Lao, Chendeng, Zou, Zhuan, Pan, Songmu, Huang, Zonggui
• Format: Article
• Language: English
• Subjects: Arthritis; Biomedical materials; Cartilage; Cartilage (articular); Cartilage diseases; Cellular manufacture; Chondrocyte dysfunction; Chondrocytes; Collagen; Collagen (type II); Collagenase 3; Cyclooxygenase-2; Cytokines; Degradation; IL-1β; Inflammation; Inflammatory response; Interleukins; Matrix metalloproteinase; Matrix metalloproteinases; Monocyte chemoattractant protein; Monocyte chemoattractant protein 1; Monocytes; NF-κB; NF-κB protein; Nitric-oxide synthase; Osteoarthritis; Oxidative stress; Prostaglandin E2; Proteins; Reactive oxygen species; Theobromine; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2020.106226

•Theobromine attenuates IL-1β- induced oxidative stress in human chondrocytes.•Theobromine mitigates IL-1β- induced increase in COX-2, PGE2, iNOS, NO, TNF-α, and MCP-1.•Theobromine prevents the loss of type II collagen by inhibiting MMP-3 and MMP-13.•Theobromine inhibits IL-1β- induced activation of IκBα/NF-κB signaling. Osteoarthritis is one of the major causes of disability in elderly adults. Chondrocytes are responsible for the formation and remodeling of articular cartilage in joint tissue. The dysfunction of chondrocytes is a significant factor in the development of osteoarthritis. In the current study, we found that theobromine, a constituent of the cacao plant, possesses a preventive effect against interleukin (IL)-1β-induced chondrocyte dysfunction. Theobromine ameliorates IL-1β-induced production of cellular reactive oxygen species (ROS) and inflammatory mediators including cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2). The presence of theobromine suppresses IL-1β-induced inducible nitro oxide synthase (iNOS) expression and cellular nitro oxide (NO) production. Theobromine also suppresses IL-1β-induced production of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1), as well as matrix metalloproteinases (MMP)-3 and MMP-13. Additionally, theobromine mitigates IL-1β-induced type II collagen degradation. Mechanistically, we show that theobromine inhibits IL-1β-induced IκBα activation, nuclear factor-κB (NF-κB) protein p65 accumulation, and transfected NF-κB promoter activity, indicating that theobromine suppresses the NF-κB pathway in chondrocytes. Collectively, our study demonstrates that the natural molecule theobromine has a protective effect to counter cytokine-induced chondrocyte dysfunction, implying its beneficial effect in the prevention of osteoarthritis.