Tormentic acid, a triterpenoid saponin, isolated from Rosa rugosa, inhibited LPS-induced iNOS, COX-2, and TNF-x3b1; expression through inactivation of the nuclear factor-x3ba;b pathway in RAW 264.7 macrophages
文摘
We previously reported that extract of Rosa rugosa root and its active triterpenoids constituents exhibit anti-nociceptive and anti-inflammatory effects in animal models. However, little is known about the effects and the molecular mechanism of the 19x3b1;-hydroxyursane-type triterpenoids. Among the tested 19x3b1;-hydroxyursane-type triterpenoids (kaji-ichigoside F1, rosamultin, euscaphic acid, tormentic acid (TA)), TA was found to most potently inhibit the production of nitric oxide (NO) in RAW 264.7 cells. We investigated the anti-inflammatory effects and its underlying molecular mechanisms of TA in lipopolysaccaride (LPS)-stimulated RAW 264.7 cells. TA dose-dependently reduced the productions of NO, prostaglandin E2 (PGE2), and tumor necrosis factor-x3b1; (TNF-x3b1;) induced by LPS. In addition, TA significantly suppressed the LPS-induced expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-x3b1; at the mRNA and protein levels. Moreover, treatment with TA decreased LPS-induced DNA binding of nuclear factor-kappa B (NF-x3ba;B) and nuclear translocation of p65 and p50 subunits of NF-x3ba;B. Consistent with these findings, TA also suppressed the LPS-stimulated degradation and phosphorylation of inhibitor of kappa B-x3b1; (Ix3ba;B-x3b1;). Taken together, these results suggest that the anti-inflammatory activity of TA is associated with the down-regulation of iNOS, COX-2, and TNF-x3b1; through the negative regulation of the NF-x3ba;B pathway in RAW 264.7 cells.