sauchinone and Osteoarthritis

Sauchinone is one of the active lignan isolated from Saururus chinensis, which has been considered to possess various pharmacological activities, such as antitumor, hepatoprotective, antioxidant, and anti-inflammatory effects. However, the functional roles of sauchinone in interleukin-1 beta (IL-1β)-stimulated human osteoarthritis (OA) chondrocytes are still unknown. Thus, in this study, we investigated the anti-inflammatory effects of sauchinone in IL-1β-stimulated chondrocytes. Our results demonstrated that sauchinone significantly attenuated NO and PGE2 production, as well as inhibited iNOS and COX-2 expression in IL-1β-stimulated OA chondrocytes. In addition, sauchinone efficiently inhibited IL-1β-induced MMP-3 and MMP-13 release in human OA chondrocytes. Furthermore, sauchinone significantly attenuated the activation of NF-κB in human OA chondrocytes. In conclusion, we showed for the first time that sauchinone inhibited inflammatory response in IL-1β-stimulated human chondrocytes probably through inhibiting the activation of NF-κB signaling pathway. These data suggest that sauchinone may be a potential agent in the treatment of OA.

Topics: Aged; Benzopyrans; Cells, Cultured; Chondrocytes; Cyclooxygenase 2; Dinoprostone; Dioxoles; Female; Humans; Inflammation; Interleukin-1beta; Matrix Metalloproteinase 13; Matrix Metalloproteinase 3; Middle Aged; Nitric Oxide; Nitric Oxide Synthase Type II; Osteoarthritis

Osteoarthritis (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.. To 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.. Our findings indicate that SAU may be a potential novel therapeutic for the treatment of OA.

Topics: Animals; Anti-Inflammatory Agents; Benzopyrans; Cell Survival; Cells, Cultured; Chondrocytes; Dioxoles; Disease Models, Animal; Extracellular Matrix; Female; Heme Oxygenase-1; Interleukin-1beta; Male; Membrane Proteins; Mice, Inbred C57BL; NF-E2-Related Factor 2; NF-kappa B; Osteoarthritis; Signal Transduction