Cryptotanshinone inhibits prostaglandin E2 production and COX-2 expression via suppression of TLR4/NF-κB signaling pathway in LPS-stimulated Caco-2 cells

Crytotanshinone (CTN), one of the main constituents of Salvia miltiorrhiza, has been known to exhibit anti-oxdative, anti-inflammatory and other important therapeutic activities. The aim of this study was to evaluate the effect of CTN on prostaglandin E2 and COX-2 production in LPS-stimulated human intestinal cells (Caco-2 cells). Caco-2 cells were stimulated with LPS in the presence or absence of CTN. The production of prostaglandin E2 (PGE(2)) was detected by ELISA. The expression of COX-2 was detected by qRT-PCR and Western blot. The extent of phosphorylation of I kappa B-alpha, NF-kappa B p65 and the expression of TLR4 were detected by western blot. The results showed that CTN dose-dependently inhibited the expression of COX-2 both in mRNA and protein levels, resulting in a decreased production of PGE(2). We also found that CTN suppressed LPS-induced NF-kappa B activation and I kappa B alpha degradation. Furthermore, CTN inhibited the expression of TLR4 up-regulated by LPS. These results suggest that CTN exerts an anti-inflammatory property by inhibiting TLR4/NF-kappa B signaling pathway and the release of pro inflammatory mediators. These findings suggest that CTN may be a therapeutic agent against intestinal inflammatory diseases.