Sauchinone inhibits IL-1β induced catabolism and hypertrophy in mouse chondrocytes to attenuate osteoarthritis via Nrf2/HO-1 and NF-κB pathways

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BackgroundOsteoarthritis (OA) is a common degenerative joint disease for which currently no anti-inflammatory therapy is available. Sauchinone (SAU), a key bioactive compound derived from Saururus chinensis, which has shown remarkable anti-inflammatory effects.MethodsTo evaluate the effect of SAU on OA progression, mouse chondrocytes were pretreated with SAU and subsequently stimulated with interleukin (IL)-1β. We found that SAU reduced the production of pro-inflammatory cytokines, such as nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), and IL-6. SAU also inhibited the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) at both the gene and protein level. Moreover, SAU promoted the expression of aggrecan, while inhibiting the expression of catabolic factors, such as matrix metalloproteinases (MMPs) and thrombospondin motifs 5 (ADAMTS-5) in mouse chondrocytes. Col X, vascular endothelial growth factor-A (VEGF)-A, and Runx2, major markers of hypertrophic chondrocytes, were markedly elevated following IL-1β stimulation, and were reduced by SAU treatment while having the opposite effect on Col II. Mechanistically, we found that SAU inhibited nuclear factor kappa B (NF-κB) and activated the Nrf2/HO-1 pathway. The beneficial effects of SAU were also observed in vivo using a mouse OA model.ConclusionsOur findings indicate that SAU may be a potential novel therapeutic for the treatment of OA.Graphical abstractHighlightsSauchinone suppressed the IL-1β-stimulated inflammation, hypertrophic shift and ECM degradation in mouse chondrocytes.Potential protective molecular mechanism of the sauchinone in IL-1β-induced mouse chondrocytes involved Nrf2/HO-1 pathway.Sauchinone attenuated progression of OA in a mouse model, and might be a promising therapeutic agent for the treatment of OA.

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