Study of Anti-inflammatory effect by Cucurbitacin E via modulation of PI3K/Akt/NF-κB pathways.

Objective: Increasing studies indicate that Cucurbitacin E (CuE), a derivative isolated from Cucurbitaceae plants may exert anti-inflammatory effect. In this study we explore the effect of CuE on TNF-α-induced inflammatory cytokines production in human synoviocytes MH7A cells, and further explore the detailed molecular mechanism involved in its anti-inflammatory effect. Materials and method: MH7A cells were stimulated with TNF-α in the presence or absence of CuE, The expression of pro-inflammatory cytokines was determined by quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA). Signal-transduction protein expression was determined by Western blot. Nuclear translocation of NF-κB p65 was determined by a confocal fluorescence microscopy. Result: CuE suppresses TNF-α-induced interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8) mRNA and protein expression in MH7A cells in a dose-dependent manner with no apparent cytotoxicity. CuE also suppressed TNF-α-induced phosphorylation of NF-κB p65, IKKα/β, IκBα as well as NF-κB p65 nuclear translocation in a dose-and time-dependent manner. Furthermore, CuE suppresses the TNF-α-induced activiation of PI3K/Akt similarly as the PI3K inhibitor LY294002,which also decreases the activation of NF-κB as well as mRNA and protein expression of IL-1β, IL-6, and IL-8 in TNF-α-induced MH7A cells. Conclusion: These findings demonstrate that Cucurbitacin E as a potential therapeutic agent for Rheumatoid arthritis can inhibits TNF-α-induced inflammatory cytokine production in human synoviocyte MH7A cells via modulation of PI3K/Akt/NF- κB pathway.