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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.