Xanthii fructus inhibits inflammatory responses in LPS-stimulated RAW 264.7 macrophages through suppressing NF-κB and JNK/p38 MAPK

Ethnopharmacological relevance: Xanthii fructus (XF) has long been used to treat a variety of inflammatory conditions in Korean traditional medicine, but the underlying mechanisms that could explain the anti-inflammatory actions of XF remain largely unknown. Aim of the study: This study aimed to elucidate the anti-inflammatory effects of X. fructus (XF) and to examine its underlying molecular mechanisms in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Materials and methods: The effect of XF on LPS-induced mRNA and protein expressions of inflammatory mediators and cytokines were determined. Moreover, the activation of the nuclear factor-kappa B (NF-kappa B) and mitogen-activated protein kinase (MAPK) signaling pathways and the expression of heme oxygenase-1 (HO-1) were explored to elucidate the anti-inflammatory mechanisms. Results: XF significantly inhibited LPS-induced production of inflammatory mediators, interleukin-6 (IL-6), nitric oxide (NO), and prostaglandin E-2 (PGE(2)), without any cytotoxicity. However, it did not affect tissue necrosis factor (TNF)-alpha or IL-1 beta production in LPS-stimulated RAW 264.7 cells. Expression levels of inducible nitric oxide synthase (iNOS) mRNA and protein were inhibited dose-dependently by XF in LPS-stimulated RAW 264.7 cells, but there were no changes in cyclooxygenase-2 (COX-2) mRNA and protein. XF significantly attenuated LPS-induced phospholylation and degradation of inhibitory kappa B alpha( (I kappa B alpha) and consequently reduced the nuclear translocation of p65 NF-kappa B. Pretreatment with XF also strongly inhibited the LPS-induced phosphorylation of p38 kinase and JNK, whereas the phosphoiylation of ERK1/2 was not affected. In addition, XF led to an increase in HO-1 expression. Conclusion: Taken together, our findings support that XF inhibits LPS-induced inflammatory responses by blocking NF-kappa B activation, inhibiting JNK/p38 MAPK phosphorylation, and enhancing HO-1 expression in macrophages, suggesting that it could be an attractive therapeutic candidate for various inflammatory diseases. (c) 2015 Elsevier Ireland Ltd. All rights reserved.