Berberine inhibits the interleukin‐1 beta‐induced inflammatory response via MAPK downregulation in rat articular chondrocytes

Abstract

Osteoarthritis (OA) is one of the most chronic degenerative arthritic diseases, which gradually results in chondrocyte changes, articular cartilage degeneration, subchondral bone sclerosis, joint pain, swelling, and dysfunction. Berberine (BBR) has various confirmed biological activities, such as anti-inflammatory and antioxidant activities. However, the effect of BBR on the production of inflammation-associated proteins, including inducible nitric oxide synthase (iNOS), cyclooxygenase (Cox)-2, metalloproteinases (MMPs), Collagen II, TNF-α, and IL-6 via the MAPK (mitogenactivated protein kinases) pathway in IL-1β-stimulated rat chondrocytes, has not yet been studied. Thus, the purpose of this study was to evaluate whether BBR would decrease the production of inflammation-associated proteins through the MAPK signal pathway. Rat chondrocytes were cultured and pretreated with BBR at different concentrations (0, 25, 50, and 100 μM) and then stimulated with or without IL-1β (10 ng/mL). The mRNA expression of iNOS, COX-2, MMP-3, MMP-13, TNF-α, and IL-6 was measured by real-time polymerase chain reaction (RT-PCR), and the protein expression of iNOS, COX-2, Collagen II, MMP-3,MMP-13, and MAPKs were measured by Western blotting. The results showed that the expression of iNOS, COX-2, MMP-3, MMP-13, TNF-α, and IL-6 increased in the IL-1β-treated group and BBR showed an ability to inhibit the elevated expression under the pretreatment. Furthermore, the IL-1β-induced downregulation of Collagen II could be ameliorated by BBR.Moreover, the expression of MAPKs was significantly decreased by BBR. These results demonstrated that BBR had the anti-catabolic and anti-inflammation abilities that were through the MAPKs in IL-1β-induced rat chondrocytes. These findings may provide a novel therapeutic choice for treatment of OA using BBR. K E Y W O R D S berberine, chondrocyte, IL-1β, MAPKs, osteoarthritis Xing Li and Peiheng He contributed equally to this study.

Membrane-Free Stem Cell Components Inhibit Interleukin-1α-Stimulated Inflammation and Cartilage Degradation In Vitro and In Vivo: A Rat Model of Osteoarthritis

“…In addition, IL-1α is liberated in an active form upon cell damage and able to activate IL-1β and product other cytokines in progressive of OA [16]. Currently, studies focusing on stem cell-based therapy or developing alternative sources of stem cells for OA treatment, regenerate cartilage and attenuate on-going inflammation [17,18]. ADSC therapy is a stem cell-based approach with potential therapeutic application for chronic diseases and is mediated via anti-inflammatory, anti-apoptotic, pro-trophic, and pro-angiogenic effects [19].…”

Nutraceutical Activity in Osteoarthritis Biology: A Focus on the Nutrigenomic Role

“…Furthermore, PI3-kinase/Akt and p38 pathways were found to be involved in berberine regulation of cytoskeletal reorganization and dedifferentiation in rabbit articular chondrocytes, ameliorating OA progression [149]. Recently, berberine was also proven to exert important anticatabolic and anti-inflammatory properties by suppressing IL-1-induced inflammation, once again through the inhibition of MAPK signaling pathway [150]. As with other active plant compounds, berberine shows issues regarding its bioavailability.…”

Gaining Insights To Understand The Anti-Inflammatory Functions of Mesenchymal Stem Cell-Derived Conditioned Medium In Combination With Stigmasterol In IL-1β-Stimulated Rat Articular Chondrocytes – An In-Vitro Approach

“…Notably, IL-1β exerts its detrimental effects on the chondrocytes by compromising the chondrocyte viability, inhibiting the anabolic processes critical to cartilage homeostasis vis-à-vis production of ECM components, impairing their fate of differentiation and dysregulating their functions to induce pro-in ammatory and pro-catabolic responses (Charlier et al, 2016). Hence IL-1β induction in chondrocytes has been employed as a conventional way to generate an OA model in vitro (Li et al, 2019).…”