Astragaloside IV Regulates STAT1/Iκ/NF-κB Signaling Pathway to Inhibit Activation of BV-2 Cells
(2.Shanghai Key Laboratory of Complex Prescriptions, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai,China 201203)
【Abstract】Objective: The study was aimed to investigate the inhibitory effect and mechanism of astragaloside IV( ASI) on the activation of microglial cells. Method: After pre-incubated with ASI for 2 h,microglial cells BV-2 were stimulated with interferon-γ( IFN-γ) for 1. 5 h and 24 h,respectively. Secretion of nitric oxide( NO) in the medium was measured by Griess method. Production of tumor necrosis factor alpha( TNF-α) was detected by ELISA approach. Cellular gene expressions of CD11 b,TNF-α,interleukin 1β( IL-1β) and induced nitric oxide synthase( i NOS) were examined by quantitative-PCR analysis. Total and phosphorylation of STAT1,IκB and NF-κB was analyzed by Western blot method. Result: ASI could significantly inhibit the increased secretion of TNF-α and NO from BV-2 cells upon IFN-γ stimulation( P < 0. 001). Further study showed that ASI significantly down-regulated gene expression of IL-1β and TNF-α( P < 0. 01,P < 0. 05) and exhibited a trend to reduce that of i NOS. IFN-γ and ASI have no obvious effect on gene expression of CD11 b. Moreover,ASI inhibited the phosphorylation of STAT1,IκB and NF-κB elicited by IFN-γ stimulation.Conclusion: ASI could restrain microglial activation through interfering STAT1 / IκB / NF-κB signaling pathway,reducing gene expression of IL-1β and TNF-α,and thus inhibiting the production of proinflammatory mediators such as NO and TNF-α.
【Keywords】 astragaloside IV; microglia cells; neuroinflammation; STAT1; IκB; NF-κB;
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