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Plumbagin inhibits LPS-induced inflammation through the inactivation of the nuclear factor-kappa B and mitogen activated protein kinase signaling pathways in RAW 264.7 cells
- Wang, Tingyu, Wu, Feihua, Jin, Zhigui, Zhai, Zanjing, Wang, Yugang, Tu, Bing, Yan, Wei, Tang, Tingting
- Food and chemical toxicology 2014 v.64 pp. 177-183
- analgesic effect, anti-inflammatory activity, cytotoxicity, inducible nitric oxide synthase, inflammation, interleukin-1beta, interleukin-6, luciferase, mechanism of action, mitogen-activated protein kinase, phosphorylation, plumbagin, secretion, signal transduction, toxicology, transcription factor NF-kappa B, tumor necrosis factor-alpha
- Plumbagin (PL) has been reported to exhibit anti-carcinogenic, anti-inflammatory and analgesic activities, but little is known about its mechanism. In this study, we investigated the anti-inflammatory property of PL and its mechanism of action. Although no significant cytotoxicity of PL was observed over the concentration range tested, PL (2.5–7.5μM) significantly and dose-dependently suppressed the secretion of pro-inflammatory mediators and inhibited the expression of TNF-α, IL-1β, IL-6 and iNOS in LPS-stimulated RAW 264.7 cells. Furthermore, PL consistently suppressed the activity of iNOS in LPS-induced RAW 264.7 cells. To elucidate the mechanism underlying the anti-inflammatory activity of PL, we assessed the effects of PL on the MAPK pathway and the activity and expression of NF-κB. These experiments demonstrated that PL significantly reduced the luciferase activity of an NF-κB promoter reporter and p65 nuclear translocation. The LPS-induced phosphorylation of MAP kinases was also attenuated by PL; significant changes were observed in the levels of phosphorylated ERK1/2, JNK and p38 MAPK. Additionally, MAPK inhibitors confirmed the inhibitory effect of PL on the MAPK pathway. Taken together, these data suggest that PL exerts its anti-inflammatory effects by down-regulating the expression of pro-inflammatory mediators through inhibition of NF-κB and MAPK signaling in LPS-stimulated RAW 264.7 cells.