Stachydrine attenuates IL-1β-induced inflammatory response in osteoarthritis chondrocytes through the NF-κB signaling pathway.

Osteoarthritis (OA) is a common degenerative joint disease that is closely associated with inflammation. Stachydrine (STA) is a bioactive alkaloid with anti-inflammatory activity. However, the role of STA in OA remains unknown. This study aimed to explore the effects of STA on OA chondrocytes in the presence of IL-1β. Primary human OA chondrocytes were pretreated with various concentrations of STA for 2 h and then stimulated with IL-1β for 24 h. Inflammatory mediators and cytokines including NO, PGE2, TNF-α and IL-6 in chondrocytes were detected to reflect inflammation status. Production of extracellular matrix (ECM) degrading enzymes including MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5 in chondrocytes was measured using ELISA. The expression levels of iNOS, COX-2, p65, p-p65, p-IκBα, and IκBα were detected by Western blot analysis. Our results showed that STA significantly suppressed IL-1β-induced inflammation with decreased levels of inflammatory mediators and cytokines including NO, PGE2, iNOS, COX-2, TNF-α and IL-6. Treatment with STA suppressed the production of ECM degrading enzymes including MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5 in IL-1β-induced chondrocytes. Furthermore, STA blocked the IL-1β-mediated potentiation of NF-κB pathway in chondrocytes. In conclusion, these findings demonstrated that STA protected chondrocytes from IL-1β-induced inflammation through the NF-κB signaling pathway.

Wu H ，Zhang M ，Li W ，Zhu S ，Zhang D ... -  《-》

Diosmetin ameliorates osteoarthritic inflammation in vivo and ECM macromolecules degradation in interleukin-1β-stimulated murine chondrocytes through the Nrf2/NF-κB pathway.

Qian L ，Li C ，Liu H ，Zhou H ，Tan T ... -  《-》

Chrysin Attenuates IL-1β-Induced Expression of Inflammatory Mediators by Suppressing NF-κB in Human Osteoarthritis Chondrocytes.

Zheng W ，Tao Z ，Cai L ，Chen C ，Zhang C ，Wang Q ，Ying X ，Hu W ，Chen H ... -  《-》

Cryptotanshinone protects against IL-1β-induced inflammation in human osteoarthritis chondrocytes and ameliorates the progression of osteoarthritis in mice.

Osteoarthritis (OA) is a common degenerative disease characterized by progressive erosion of articular cartilage, subchondral bone sclerosis and synovitis. Cryptotanshinone (CTS), an active component extracted from the root of Salvia miltiorrhiza Bunge, has been shown to have potent anti-inflammatory effects. However, its effects on OA have not been clearly elucidated. This study aimed to assess the effect of CTS on human OA chondrocytes and mice OA models. Human OA chondrocytes were pretreated with CTS (5, 10 and 20μM) for 2h and subsequently stimulated with IL-1β for 24h. Production of NO, PGE2, IL-6, TNF-α was evaluated by the Griess reaction and ELISA. The protein expression of COX-2, iNOs, MMP-3, MMP13, COX-2, ADAMTS-5, JNK, p-JNK, ERK, p-ERK, p38, p-p38, p-IKKα/β, p65, p-p65, IκB-α, and p-IκB-α was tested by Western blot. In vivo, the severity of OA was determined by histological analysis. We found that CTS significantly inhibited the IL-1β-induced production of NO and PGE2; expression of COX-2, iNOS, MMP-3, MMP-13, and ADAMTS-5. Furthermore, CTS in dramatically suppressed IL-1β-stimulated NF-κB and MAPK activation. Immunofluorescence staining demonstrated that CTS could suppress IL-1β-induced phosphorylation of p65 nuclear translocation. In vivo, treatment of CTS prevented the destruction of cartilage and the thickening of subchondral bone in mice OA models. These results indicate that the therapeutic effect of CTS on OA is accomplished through the inhibition of both NF-κB and MAPK signaling pathways. Our findings provide the evidence to develop CTS as a potential therapeutic agent f or patients with OA.

Feng Z ，Zheng W ，Li X ，Lin J ，Xie C ，Li H ，Cheng L ，Wu A ，Ni W ... -  《-》

Luteolin inhibits IL-1β-induced inflammation in rat chondrocytes and attenuates osteoarthritis progression in a rat model.

Osteoarthritis (OA) is a joint disease characterized by inflammation and cartilage degradation. Accumulating evidence has demonstrated that luteolin, a natural flavonoid, has anti-inflammatory and anticatabolic effects. The present study aimed to assess the protective effect of luteolin on interleukin (IL)-1β-stimulated rat chondrocytes and a monosodium iodoacetate (MIA)-induced model of OA. Rat chondrocytes were pretreated with luteolin (0, 25, 50, and 100 μM for 12 h) prior to stimulation with IL-1β (10 ng/ml for 24 h). Nitric oxide (NO) production was determined using the Griess method. Production of prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and matrix metalloproteinase-2, -8, and -9 (MMP-2, MMP-8 and MMP-9) was measured by an enzyme-linked immunosorbent assay (ELISA). Protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), MMP-1, MMP-3, MMP-13, p65, p-p65, IκB, and p-IκB were determined by Western blotting. The OA rats received luteolin (10 mg/kg/day) by gavage in vivo. Morphological and ultrastructural scanning electron microscopy (SEM) observations were performed to assess the severity of OA at 45 days following MIA injection. Collagen II protein expression was determined by immunohistochemistry. In this study, luteolin considerably reduced the IL-1β-induced production of NO, PGE2, TNF-α, MMP-2, MMP-8 and MMP-9 and the expression of COX-2, iNOS, MMP-1, MMP-3 and MMP-13. Luteolin reversed the degradation of collagen II induced by IL-1β. Luteolin also significantly inhibited IL-1β-induced phosphorylation of NF-κB in vitro. Luteolin treatment prevented cartilage destruction and enhanced collagen II expression in OA rats in vivo. Overall, our findings suggest that luteolin may be a useful therapeutic agent for patients with OA.

Fei J ，Liang B ，Jiang C ，Ni H ，Wang L ... -  《-》