红藤中sargentol对PC12细胞的神经保护作用和分子对接研究  

Neuroprotective effect and molecular docking of sargentol isolated from Sargentodoxa cuneata on PC12 cells

作　　者：汤建 孙惠芳[2] 张腾腾 安凤霞 耿春叶 闻崇炜[2] TANG Jian;SUN Hui-fang;ZHANG Teng-teng;AN Feng-xia;GENG Chun-ye;WEN Chong-wei(School of Chinese Medicine,Bozhou University,Bozhou 236800,China;School of Pharmacy,Jiangsu University,Zhenjiang 212013,China)

机构地区：[1]亳州学院中药学院,亳州236800 [2]江苏大学药学院,镇江212013

出　　处：《天然产物研究与开发》2021年第12期2067-2072,共6页Natural Product Research and Development

基　　金：安徽省科技重大专项(18030701163);安徽省高等学校自然科学研究项目(KJ2019ZD80);安徽省高校学科(专业)拔尖人才学术资助项目(gxbjZD50);亳州市重大专项(BKJZD201801)。

摘　　要：红藤提取物具有抗炎、抗氧化和神经保护活性,从中分离得到苯丙素类化合物sargentol。为研究其神经保护活性和潜在的作用机制,本文中采用过氧化氢(H_(2)O_(2))、鱼藤酮(rotenone)、叠氮钠(NaN_(3))致PC12细胞损伤模型评价该化合物对细胞存活率的影响,采用DCFH-DA探针法检测损伤细胞内氧化应激(ROS)水平。进一步采用AutoDock Vina软件与14种蛋白进行分子对接,根据打分值虚拟筛选sargentol可能的结合靶点蛋白和活性机制。发现sargentol(0.1、1、10μmol/L)对0.5 mmol/L的H_(2)O_(2)致PC12细胞损伤具有良好的保护作用(P<0.05),且明显抑制PC12细胞内ROS水平;Sargentol对鱼藤酮(10μmol/L)损伤的PC12细胞有中等强度的保护作用(P>0.05);对NaN_(3)致损的PC12细胞仅有微弱保护作用(P>0.05)。分子对接显示,sargentol与5D3I、2Y37、1E7V、4L7B和3RZF等5种靶点蛋白有良好的结合能力,其中与5D3I(Toll样受体2)和2Y37(诱导性一氧化氮合酶)的结合能最高,均为-7.7 kcal/mol。这意味着sargentol可能通过抗氧化和抗炎机制发挥神经保护作用。Sargentodoxa cuneata extracts possessed anti-inflammatory,antioxidant,and neuroprotective effects.Herein,a phenylpropanoid sargentol from this plant was studied to evaluate its neuroprotective effect using hydrogen peroxide(H_(2)O_(2)),rotenone,sodium azide(NaN_(3))induced damage in PC12 cell,and the cell viability was detected by MTT method.DCFH-DA probe was used to test the intracellular reactive oxygen species(ROS)level.AutoDock Vina was used to dock sargentol with 14 selected target proteins,to virtually screen the potential target according to the docking scores.The pretreatment of PC12 cell with sargentol(0.1,1,10μmol/L)obviously increased cell viability damaged by H_(2)O_(2) (P<0.05)and inhibited the ROS level.While sargentol had moderate protective effect against rotenone injured PC12 cell(P>0.05),only had slight effect on NaN_(3) injured PC12 cell(P>0.05).Sargentol had higher binding affinity with proteins 5D3I,2Y37,1E7V,4L7B and 3RZF,and possessed highest affinity of-7.7 kcal/mol with 5D3I(TLR2)and 2Y37(iNOS).These findings suggested that sargentol might be serving as a novel potential resource for neuroprotection,which could be associated with ROS and inflammation.

关 键 词：sargentol 神经保护 氧化应激 炎症 分子对接 

分 类 号：R93[医药卫生—生药学]