<p>S-Allylmercaptocysteine Targets Nrf2 in Osteoarthritis Treatment Through NOX4/NF-κB Pathway</p>

Abstract

Purpose This study aimed to explore the potential role and mechanism of garlic-derived S-allylmercaptocysteine (SAMC), the major water-soluble fraction of garlic, in osteoarthritis (OA) both in vivo and in vitro. Methods The effect of SAMC in a surgical-induced OA model was examined by X-ray, staining, ELISA, and immunoblotting. Then the key role of Nrf2 by SAMC treatment in IL-1β stimulated chondrocytes in vitro was determined by gene-knockdown technique. Results SAMC could stabilize the extracellular matrix (ECM) by decreasing metalloproteinase (MMPs) expression to suppress type II collagen degradation in OA rats. The inflammatory cytokines, such as IL-1β, TNF-α, and IL-6, were elevated in OA, which could be down-regulated by SAMC treatment. This effect was parallel with NF-κB signaling inhibition by SAMC. As oxidative stress has been shown to participate in the inflammatory pathways in OA conditions, the key regulator Nrf2 in redox-homeostasis was evaluated in SAMC-treated OA rats. Nrf2 and its down-stream gene NQO-1 were activated in the SAMC-treated group, accompanied by NAD(P)H oxidases 4 (NOX4) expression down-regulated. As a result, the toxic lipid peroxidation byproduct 4-hydroxynonenal (4HNE) was reduced in articular cartilage. In IL-1β-stimulated primary rat chondrocytes, which could mimic OA in vitro, SAMC could ameliorate collagen destruction, inhibit inflammation, and maintain redox-homeostasis. Interestingly, after Nrf2 gene knockdown by adenovirus, the protective effect of SAMC in IL-1β-stimulated chondrocytes disappeared. Conclusion Overall, our study demonstrated that SAMC targeted Nrf2 to protect OA both in vivo and in vitro, which would be a new pharmaceutical way for OA therapy.

Carnosine Alleviates Knee Osteoarthritis and Promotes Synoviocyte Protection via Activating the Nrf2/HO-1 Signaling Pathway: An In-Vivo and In-Vitro Study

“…The Nrf2 signaling pathway is involved in the regulation of oxidative stress, inflammation, immunity, bone metabolism, and cartilage [ 108 ]. In rodent pain models, activating the Nrf2 signaling pathway reduced inflammatory and neuropathic pain [ 109 ]. In a recent study, a sulforaphane-activated Nrf2 signaling pathway was found to reduce allodynia and hyperalgesia while augmenting morphine’s antinociception [ 110 ].…”

Association between Usual Dietary Intake of Food Groups and DNA Methylation and Effect Modification by Metabotype in the KORA FF4 Cohort

“…This gene is associated with different conditions, such as cartilage degradation [37], cardiac hypertrophy [38], and renal cell carcinoma [39]. The literature supports the idea that components of this food group can be connected to all of these conditions [40][41][42].…”

The Role Played by Ferroptosis in Osteoarthritis: Evidence Based on Iron Dyshomeostasis and Lipid Peroxidation

“…Karakurum et al [ 61 ] reported that serum MDA levels were positively correlated with degeneration severity in rabbit models of ACLT-induced OA. Yang et al [ 62 ] found increased MDA and GSSG levels and decreased GSH and GPX levels in the serum of ACLT-induced OA rat models compared to controls. Goranov et al [ 63 ] and Chang et al [ 64 ] found similar results in the same OA model of dogs and obese rats.…”