摘要
本实验以金边桑叶为研究对象,通过水提法制得粗提物AWE,后经大孔树脂分离纯化制得金边桑叶多酚提取物AWF,在探讨AWE和AWF体外抗氧化(清除自由基)能力的基础上,进一步探究了AWF对乙酰氨基酚(APAP)诱导的小鼠急性肝损伤的保护作用及其作用机制。AWE和AWF多酚含量分别为224.9±1.5和608.7±16.4μg GAE/mg extract,且AWF对DPPH和ABTS自由基具有较强的清除能力,其IC50值分别为4.46和41.25μg/m L。中、高剂量AWF(200和400 mg/kg·bw)灌胃处理能显著改善APAP诱导的小鼠急性肝损伤,使肝损伤小鼠血清中ALT、AST和LDH活性及MDA含量降低(P<0.05或P<0.001),血清中SOD和CAT及肝脏中GSH-Px活性升高(P<0.01或P<0.001),免疫组化结果也显示肝脏组织损伤情况明显减轻。此外AWF可显著抑制损伤肝脏组织中MAPKs及促凋亡蛋白caspase-3/9的活化,下调促凋亡蛋白Bax并上调抗凋亡蛋白Bcl2的表达量。实验结果表明,AWF可改善APAP诱导的小鼠急性肝损伤,其作用可能是通过调控MAPKs/apoptosis级联反应,发挥抗氧化和抗凋亡作用来实现的。
In this experiment,a crude extract named as AWE was extracted by water extraction from Acalypha wilkesiana leaves,and then a polyphenol-enriched fraction was prepared by macroporous resin,designated as AWF. Based on the results of free radical scavenging activities of AWE and AWF in vitro,the hepatoprotective effects of AWF and the underlying mechanisms were further investigated by APAP-induced acute liver injury mice model. Results showed that the polyphenol contents in AWE and AWF reached 224. 9 ± 1. 5 and 608. 7 ± 16. 4 μg GAE/mg extract,respectively. AWF exhibited strong scavenging abilities on DPPH and ABTS free radicals,the IC50 s were 4. 46 and 41. 25 μg/m L,respectively. AWF( 200 and 400 mg/kg·bw) pretreatment significantly alleviated APAP-induced acute liver injury,as evidenced by the decreased serum levels of ALT,AST,LDH,and MDA( P 〈 0. 05 or P 〈 0. 001),and the elevated activities of SOD,CAT,and GSH-Px( P 〈 0. 01 or P 〈 0. 001),the results of which were further confirmed by the histopathological analysis. Moreover,AWF remarkably inhibited the activation of MAPKs and proapoptotic protein caspase-3/9,down-regulated the expression level of proapoptotic protein Bax and restored the expression level of antiapoptotic protein Bcl2.These results indicate that AWF possesses hepatoprotective effects against APAP-induced liver injury,which may be attributed to the antioxidant and antiapoptotic effects through the modification of MAPKs/apoptosis cascade reaction.
作者
吴黉坦
张友珍
黄立森
庞海月
陈煜沛
王贵弘
叶子坚
刘华欣
WU Hong-tan;ZHANG You-zlien;HUANG Li-sen;PANG Hai-yue;CHEN Yu-pei;WANG Gui-liong;YE Zi-jian;LIU Hua-xin(Department o f Medical Technology,Xiarnen Medical College;Application Technique Engineering Center of Natural Cosmeceuticals,College of Fujian Province;Department of Basic Medicine,Xiamen Medical College;Key Laboratory of Functional and Clinical Translational Medicine,Fujian Proincc University,Xiamen 361023,China)
出处
《天然产物研究与开发》
CAS
CSCD
北大核心
2018年第6期944-950,共7页
Natural Product Research and Development
基金
福建省高校杰出青年科研人才培育计划
厦门医学院校级科研计划(博士启动基金)(K2016-09)
关键词
金边桑叶
急性肝损伤
抗氧化
抗凋亡
Acalypha wilkesiana leaves
acute liver injury
antioxidant
antiapoptotic effect