Tormentic acid, a triterpenoid saponin, isolated from Rosa rugosa, inhibited LPS-induced iNOS, COX-2, and TNF-α expression through inactivation of the nuclear factor-κb pathway in RAW 264.7 macrophages.

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 19α-hydroxyursane-type triterpenoids. Among the tested 19α-hydroxyursane-type triterpenoids (kaji-ichigoside F(1), 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 E(2) (PGE(2)), and tumor necrosis factor-α (TNF-α) induced by LPS. In addition, TA significantly suppressed the LPS-induced expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-α at the mRNA and protein levels. Moreover, treatment with TA decreased LPS-induced DNA binding of nuclear factor-kappa B (NF-κB) and nuclear translocation of p65 and p50 subunits of NF-κB. Consistent with these findings, TA also suppressed the LPS-stimulated degradation and phosphorylation of inhibitor of kappa B-α (IκB-α). Taken together, these results suggest that the anti-inflammatory activity of TA is associated with the down-regulation of iNOS, COX-2, and TNF-α through the negative regulation of the NF-κB pathway in RAW 264.7 cells.

An HJ ，Kim IT ，Park HJ ，Kim HM ，Choi JH ，Lee KT ... -  《-》

Anti-inflammatory activities of ent-16alphaH,17-hydroxy-kauran-19-oic acid isolated from the roots of Siegesbeckia pubescens are due to the inhibition of iNOS and COX-2 expression in RAW 264.7 macrophages via NF-kappaB inactivation.

Park HJ ，Kim IT ，Won JH ，Jeong SH ，Park EY ，Nam JH ，Choi J ，Lee KT ... -  《EUROPEAN JOURNAL OF PHARMACOLOGY》

Zedoarondiol isolated from the rhizoma of Curcuma heyneana is involved in the inhibition of iNOS, COX-2 and pro-inflammatory cytokines via the downregulation of NF-kappaB pathway in LPS-stimulated murine macrophages.

Cho W ，Nam JW ，Kang HJ ，Windono T ，Seo EK ，Lee KT ... -  《-》

Euscaphic acid isolated from roots of Rosa rugosa inhibits LPS-induced inflammatory responses via TLR4-mediated NF-κB inactivation in RAW 264.7 macrophages.

As an attempt to search for bioactive natural products exerting anti-inflammatory activity, we have evaluated the anti-inflammatory effects of euscaphic acid (19α-hydroxyursane-type triterpenoids, EA) isolated from roots of Rosa rugosa and its underlying molecular mechanisms in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. EA concentration-dependently reduced the production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) induced by LPS in RAW 264.7 macgophages. Consistent with these data, expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein and iNOS, COX-2, TNF-α, and IL-1β mRNA were inhibited by EA in a concentration-dependent manner. In addition, EA attenuated LPS-induced DNA binding and transcriptional activity of nuclear factor-kappa B (NF-κB), which was accompanied by a parallel reduction of degradation and phosphorylation of inhibitory kappa Bα (IκBα) and consequently by decreased nuclear translocation of p65 subunit of NF-κB. Pretreatment with EA significantly inhibited the LPS-induced phosphorylation of IκB kinase β (IKKβ), p38, and JNK, whereas the phosphorylation of ERK1/2 was unaffected. Furthermore, EA interfered with the LPS-induced clustering of TNF receptor-associated factor 6 (TRAF6) with interleukin receptor associated kinase 1 (IRAK1) and transforming growth factor-β-activated kinase 1 (TAK1). Taken together, these results suggest that EA inhibits LPS-induced inflammatory responses by interference with the clustering of TRAF6 with IRAK1 and TAK1, resulting in blocking the activation of IKK and MAPKs signal transduction to downregulate NF-κB activations.

Kim IT ，Ryu S ，Shin JS ，Choi JH ，Park HJ ，Lee KT ... -  《-》

Anti-inflammatory effect of allylpyrocatechol in LPS-induced macrophages is mediated by suppression of iNOS and COX-2 via the NF-kappaB pathway.

Sarkar D ，Saha P ，Gamre S ，Bhattacharjee S ，Hariharan C ，Ganguly S ，Sen R ，Mandal G ，Chattopadhyay S ，Majumdar S ，Chatterjee M ... -  《INTERNATIONAL IMMUNOPHARMACOLOGY》