Echinocystic Acid Inhibits IL-1β-Induced COX-2 and iNOS Expression in Human Osteoarthritis Chondrocytes

Abstract

Echinocystic acid (EA), a pentacyclic triterpene isolated from the fruits of Gleditsia sinensis Lam, displays a range of pharmacological activities including anti-inflammatory and antioxidant effects. However, the effect of EA on IL-1β-stimulated osteoarthritis chondrocyte has not been reported. The purpose of this study was to assess the effects of EA on IL-1β-stimulated human osteoarthritis chondrocyte. Chondrocytes were stimulated with IL-1β in the absence or presence of EA. NO and PGE2 production were measured by Griess reagent and ELISA. The expression of COX-2, iNOS, nuclear factor-κB (NF-κB), inhibitory kappa B (IκBα), c-Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK) were detected by Western blot analysis. The results showed that EA suppressed IL-1β-induced collagenase-3 (MMP-13), NO, and PGE2 production in a dose-dependent manner. IL-1β up-regulated the expression of COX-2 and iNOS, and the increase was inhibited by EA. Furthermore, IL-1β-induced NF-κB and mitogen-activated protein kinase (MAPK) activation were inhibited by EA. In conclusion, EA effectively attenuated IL-1β-induced inflammatory response in osteoarthritis chondrocyte which suggesting that EA may be a potential agent in the treatment of osteoarthritis.

The triterpene echinocystic acid and its 3-O-glucoside derivative are revealed as potent and selective glucocorticoid receptor agonists

“…It is proposed that the anti-inflammatory action of EAs is mediated through NF-κB inactivation. Thus, echinocystic acid is shown to suppress the lipopolysaccharide-and the IL-1β-induced iNOS, and to inhibit pro-inflammatory cytokines expression, IL-6, IL-1β and TNF-α, via inhibition of IKKβ phosphorylation and/or NF-κB inactivation in several type of cells, particularly in macrophages (Ryu et al, 2013;Hyam et al, 2013;Joh et al, 2014, Ma et al, 2016. In addition, echinocystic acid is shown to inhibit the TPA-induced myeloperoxidase activity, (Joh et al, 2014) and to down-regulate the expression of nitric oxide synthase, cyclooxygenase-2, and that of the inflammatory mediators, nitric oxide and prostaglandin E2, (Gene et al, 1996;Joh et al, 2012, Ma et al, 2016.…”

Carboxymethyl‑chitosan attenuates inducible nitric oxide synthase and promotes interleukin‑10 production in rat chondrocytes

“…Inhibition of NO production is another potential strategy to treat OA as NO production is closely associated with inflammatory reactions (10). Chemical substances including echinocystic acid, selenomethionine and piperine have been identified in previous studies as inhibitors of iNOS production and therefore attenuators of inflammation (29)(30)(31). In the present study, it was revealed that CM-chitosan inhibits iNOS production and upregulates the anti-inflammatory cytokine IL-10 mRNA and protein production in LPS-induced chondrocytes.…”

Piperlongumine attenuates IL-1β-induced inflammatory response in chondrocytes

“…COX-2, known as the rating limiting enzyme, could produce the inflammatory mediator PGE2 in chondrocytes. In addition, IL-1β was found to up-regulate the expression of iNOS and COX-2, which lead to elevated production of NO and PGE2, respectively [21,22]. Besides, PLM has been reported to have anti-inflammatory properties.…”