标题：Anti-neuroinflammation activity of acetylpuerarin mediated by a PKC-delta-dependent caspase signaling pathway: in vivo and in vitro studies
作者：Cai, Q. Y.; Liu, X. L.; Zhang, X. Q.; Liu, Y. X.; Li, M.; Zhao, C. Z.; Zhang, X. M.; Meng, Q. H.
作者机构：[Cai, Q. Y.; Liu, Y. X.; Li, M.; Meng, Q. H.] Weifang Med Univ, Coll Nursing, 7166 Bao Tong Xi St, Weifang 261053, Shandong, Peoples R China.; [Liu, 更多
通讯作者地址：[Meng, QH]Weifang Med Univ, Coll Nursing, 7166 Bao Tong Xi St, Weifang 261053, Shandong, Peoples R China.
摘要：Objective: This study was performed to evaluate the regulating effects of acetylpuerarin on inflammation in an Alzheimer's disease (AD) rat model and an inflammatory cell model. Methods: Healthy female Wistar rats and mouse BV2 microglia cells were selected. AD rat models were established with the method of bilateral intrahippocampal amyloid-beta (A beta)1-42 injections and the inflammatory cell models were established using A beta(25-35)-induced mouse BV2 microglia cells. The cytotoxicity of acetylpuerarin on BV2 microglial cells was detected by MTT assay and the morphological changes of BV2 microglia cells were observed under inverted phase contrast microscope. As inflammatory parameters, the expressions of IL-1 beta, iNOS, IL-6 and TNF-alpha were examined by Elisa, Immunohistochemistry, Quantitative real-time PCR (qRT-PCR), Western blot and Immunofluorescence analyses. We also examined the acetylpuerarin's effect on the activity of PKC-delta, IKK beta and caspase-8/caspase-3 pathway. Results: Acetylpuerarin exerted no significant cytotoxicity on BV2 microglia cells and was applied in all subsequent experiments. Acetylpuerarin treatment mitigated A beta(25-35)-induced morphological changes associated with microglia activation. Moreover, the expressions of caspase-8, cleaved caspase-3, PKC-delta, IKK beta,.iNOS, IL-1 beta and TNF-alpha in A beta(25-35) stimulated BV2 microglia cells were significantly suppressed by acetylpuerarin and in a dose-dependent manner. Additionally, the expression of IL-1 beta in hippocampus and the level of IL-6 in serum of A beta(1-42) treated rat were reduced by acetylpuerarin and in a concentration-dependent manner. Conclusion: Our results suggest that acetylpuerarin's anti-inflammation mechanism on AD may be mediated through the PKC-delta-dependent caspase signalling pathway.