查尔酮类似物清除DPPH自由基和保护H_(2)O_(2)诱导的PC12细胞损伤的抗氧化活性  

The antioxidant activity of chalcones analogues in scavenging DPPH free radical and protecting against H_(2)O_(2)-induced PC12 cell injury

作　　者：黄丽丽 陈婵婵 汪佳兵 张佳枫 吴建章 HUANG Lili;CHEN Chanchan;WANG Jiabing;ZHANG Jiafeng;WU Jianzhang(Department of Pharmacy,Ningbo Medical Centre Lihuili Hospital,Ningbo 315040,China;Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou 325035,China;Department of Pharmacy,Taizhou Municipal Hospital,Municipal Hospital Affiliated to Medical School of Taizhou University,Taizhou 318000,China)

机构地区：[1]宁波市医疗中心李惠利医院药剂科,浙江宁波315040 [2]温州医科大学药学院化学生物学研究中心,浙江温州325035 [3]台州市立医院台州学院附属市立医院药剂科,浙江台州318000

出　　处：《温州医科大学学报》2021年第7期542-547,553,共7页Journal of Wenzhou Medical University

基　　金：国家自然科学基金资助项目(82003755);宁波市医学科技计划项目(2019Y07);台州市科技计划项目(1901ky48)。

摘　　要：目的:探究合成的查尔酮类似物清除DPPH自由基和保护H_(2)O_(2)诱导PC12细胞损伤的抗氧化活性。方法:将PC12细胞分为对照组(DMSO组)、损伤组(H_(2)O_(2)组)、查尔酮类似物+H_(2)O_(2)组和阳性对照组(槲皮素+H_(2)O_(2)组)。设计合成16个查尔酮类似物,通过DPPH自由基清除实验检测自由基清除活性;MTT法检测细胞活性;MDA试剂盒检测脂质过氧化;Hoechst染色检测细胞凋亡;Western blot法检测cleaved-caspase-3、Bcl-2和Bax蛋白表达。结果:筛选得到活性佳、毒性小的抗氧化剂13。与DMSO组比较,H_(2)O_(2)组的细胞存活率、Bcl-2蛋白表达显著下降,而cleaved-caspase-3和Bax蛋白表达、MDA含量显著增加(P<0.05);与H_(2)O_(2)组比较,化合物13组呈剂量依赖性提高细胞存活率,增加Bcl-2蛋白的表达,减少cleaved-caspase-3和Bax蛋白的表达,降低MDA水平(P<0.05)。结论:新型查尔酮类似物13抑制H_(2)O_(2)诱导PC12的细胞凋亡,具有良好的抗氧化活性。Objective:To investigate the antioxidant activity of the synthesized chalcone analogues in scavenging DPPH free radical and protecting against H_(2)O_(2)-induced PC12 cell injury.Methods:PC12 cells were divided as control group(DMSO group),injury group(H_(2)O_(2) group),chalcone analogue+H_(2)O_(2) group and positive control group(quercetin+H_(2)O_(2) group).Sixteen chalcone analogues were designed and synthesized.DPPH assay was used to detect free radical scavenging activity;MTT assay was used to detect cell activity;MDA kit was used to detect lipid peroxidation;Hoechst staining was used to detect cell apoptosis;Western blot was used to detect cleaved-caspase-3,Bcl-2 and Bax protein expression.Results:Antioxidant 13 with excellent activity and low toxicity was obtained.Compared with DMSO group,the cell survival rate and Bcl-2 protein expression were decreased significantly,but cleaved-caspase-3 and Bax protein expression,MDA content were increased significantly in H_(2)O_(2) group(all P<0.05);Compared with H_(2)O_(2) group,cell survival rate was increased,Bcl-2 protein expression was up-regulated,cleaved-caspase-3 and Bax expression was down-regulated,MDA level were decreased in a dose-dependent manner by group 13 treatment(all P<0.05).Conclusion:The novel chalcone analogue 13 can inhibit H_(2)O_(2)-induced PC12 cells apoptosis,which has good antioxidant activity.

关 键 词：查尔酮类似物 DPPH自由基 过氧化氢 PC12细胞 细胞凋亡 

分 类 号：R914[医药卫生—药物化学]