灯盏乙素
神经炎症
PI3K/AKT/mTOR通路
小胶质细胞
神经保护
药理学
蛋白激酶B
医学
细胞凋亡
炎症
化学
免疫学
生物化学
作者
Zhao-Da Duan,Haolun Chen,Wei Miao,Junlin He,Dongsheng Xu,Zhi Qi,Li Yang,Jia Wang,Cheng-Shong Wu
摘要
Abstract Microglia are resident immune cells in the central nervous system that are rapidly activated to mediate neuroinflammation and apoptosis, thereby aggravating brain tissue damage after ischemic stroke (IS). Although scutellarin has a specific therapeutic effect on IS, the potential target mechanism of its treatment has not been fully elucidated. In this study, we explored the potential mechanism of scutellarin in treating IS using network pharmacology. Lipopolysaccharide (LPS) was used to induce an in vitro BV‐2 microglial cell model, while middle cerebral artery occlusion (MCAO) was used to induce an in vivo animal model. Our findings indicated that scutellarin promoted the recovery of cerebral blood flow in MCAO rats at 3 days, significantly different from that in the MCAO group. Western blotting and immunofluorescence revealed that scutellarin treatment of BV‐2 microglial cells resulted in a significant reduction in the protein expression levels and incidence of cells immunopositive for p‐NF‐ κ B, TNF‐ α , IL‐1 β , Bax, and C‐caspase‐3. In contrast, the expression levels of p‐PI3K, p‐AKT, p‐GSK3 β , and Bcl‐2 were further increased, significantly different from those in the LPS group. The PI3K inhibitor LY294002 had similar effects to scutellarin by inhibiting neuroinflammation and apoptosis in activated microglia. The results of the PI3K/AKT/GSK3 β signaling pathway and NF‐ κ B pathway in vivo in MCAO models induced microglia at 3 days were consistent with those obtained from in vitro cells. These findings indicate that scutellarin plays a neuroprotective role by reducing microglial neuroinflammation and apoptosis mediated by the activated PI3K/AKT/GSK3 β /NF‐ κ B signaling pathway.
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