Ginkgolide C slows the progression of osteoarthritis by activating Nrf2/HO-1 and blocking the NF-κB pathway

Abstract

Osteoarthritis (OA) is driven by chronic low-grade inflammation and subsequent cartilage degradation. OA is the most prevalent degenerative joint disease worldwide, and its treatment remains a challenge. The aim of this study was to explore the potential effects and mechanism underlying the anti-OA properties of ginkgolide C (GC). Protective effects of GC on hydrogen peroxide (H2O2)-treated rat chondrocytes were evaluated using ELISA, qPCR, western blot analysis, flow cytometry, ROS detection and immunofluorescence in vitro. Ameliorating effects of GC on cartilage degeneration in rats were evaluated through behavioral assays, microcomputed tomography, histopathological analysis, western blot analysis and ELISA in vivo. In vitro, GC treatment inhibited the release of pro-apoptotic factors induced by H2O2 and promoted the release of the anti-apoptotic proteins. In addition, GC decreased the expression of matrix metalloproteinase (MMP3 and MMP13), thrombospondin motifs 4 (ADAMTS4), and inflammatory mediators inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and SOX9 thereby inhibiting extracellular matrix (ECM) degradation. Mechanistically, GC exerts its anti-apoptotic and anti-inflammatory effects by upregulating the oxidative stress signaling Nrf2/HO-1 pathway and preventing p65 from binding to DNA. Similarly, In a rat model with post-traumatic OA (PTOA) induced by anterior cruciate ligament transection (ACLT), GC inhibited joint pain, cartilage destruction, and abnormal bone remodeling of subchondral bone. GC inhibited H2O2-induced chondrocyte apoptosis through Nrf2/HO-1 and NF-κB axis, exerted anti-inflammatory effects, and inhibited cartilage degeneration in rat OA. Our findings advanced the concept that GC may contribute to cartilage metabolism through anti-inflammatory and anti-apoptotic effects, and the identified GC is a potential therapeutic agent for the treatment of OA.

Asiatic acid inhibits rheumatoid arthritis fibroblast‐like synoviocyte growth through the Nrf2/HO‐1/NF‐κB signaling pathway

“…Our results showed that Nrf2 and HO-1 expressions were activated whereas NF-κB expression was suppressed in the cells with increasing AA drug concentration. Ma et al also demonstrated that Nrf2/HO-1 negatively regulated the activation of the proinflammatory signaling molecule NF-κB (Ma et al, 2022), thus inhibiting RA-FLS proliferation as well as promoting RA-FLS apoptosis (Nejatbakhsh Samimi et al, 2020). Nrf2 is an important intracellular transcription factor that is sensitive to redox reaction (Yan et al, 2017).…”

Augmenting mesenchymal stem cell therapy for osteoarthritis via inflammatory priming: a comparative study on mesenchymal stem cells derived from various perinatal tissue sources

“…For the in vitro model of OA-like ACs, H 2 O 2 (Jing Rui, China) was added to the ACs medium to induce ACs expressing an OA-like phenotype (ACs + H 2 O 2 ) ( Ma et al, 2022 ; Chen et al, 2023 ; Yagi et al, 2023 ). Briefly, the ACs were treated with the conditioned medium for 24 h. Then, the OA-like ACs were co-cultured with different MSCs before and after IL-1β treatment (UC-MSCs, UC-MSCs + IL-1β, FP-MSCs, FP-MSCs + IL-1β, CPJ-MSCs, CPJ-MSCs + IL-1β).…”

Oleanolic acid, a small-molecule natural product, inhibits ECM degeneration in osteoarthritis by regulating the Hippo/YAP and Wnt/β-catenin pathways

“…In addition, the extraction of rat cartilage tissue proteins was performed by referring to a previous study. 41,42 At the end of 8 weeks of OLA intervention, the dissected cartilages were removed from the right knee joint of the rat (use a scalpel [11#] to cut the cartilage multiple times) and homogenized in 1 mL PBS ( pH 7.4) containing protease inhibitors by shaking with 1.5 mm glass beads in a Mini-BeadBeater (BioSpec, USA) at 4800 oscillations min −1 for 3 min. The tissue homogenates were immediately centrifuged twice at 12 000g for 15 min at 4 °C to isolate the supernatant.…”