金合欢素对丝裂原蛋白激酶p38α活性抑制作用的研究

Study on the Inhibitory Activity of Acacetin on Mitogen-Activated Protein Kinase p38α

目的探讨金合欢素对丝裂原蛋白激酶p38α(p38αMAPK)的抑制作用。方法应用分子对接软件Autodock Vina将金合欢素与靶酶三维晶体结构1KV2的活性位点进行分子对接,而后利用脂多糖诱导的小鼠RAW 264.7细胞炎症模型验证金合欢素对p38αMAPK的抑制作用。结果金合欢素可结合于1KV2的活性位点处而阻碍底物三磷腺苷的进入,对p38αMAPK的生物学功能产生抑制作用。与模型组相比,阳性对照药地塞米松和金合欢素不同浓度干预后可明显下调小鼠RAW 264.7细胞炎症模型细胞上清液中一氧化氮和肿瘤坏死因子-α水平(P<0.05)。结论金合欢素可能是通过作用于p38αMAPK活性位点而发挥抗炎的药理活性。

Objective To investigate the inhibitory activity of acacetin on mitogen-activated protein kinase p38α(p38αMAPK).Methods The macromolecular docking software Autodock Vina was used for macromolecular docking between acacetin and the active site 1KV2 of the target enzyme 3D structure,and then the lipopolysaccharide(LPS)-induced mouse RAW264.7 cell inflammation model was used to validate the inhibitory activity of acacetin on p38αMAPK.Results Acacia can bind to the active site of 1KV2 and inhibit the entry of substrate adenosine triphosphate,thus inhibiting the biological function of p38αMAPK.Compared with the model group,the levels of nitric oxide and tumor necrosis factor-αin the supernatant of RAW 264.7 cell inflammatory model cells were significantly reduced after the intervention of Dexamethasone and acacillin at different concentrations and doses(P<0.05).Conclusion Acacetin can act on the active site of p38αMAPK to produce the anti-inflammatory activity.