基于FoxO信号通路探究鲜参对心肌缺血保护作用机制  

Molecular mechanisms of fresh Panax ginseng in treating myocardial ischemia based on FoxO signaling pathway

作　　者：朱雨欣 亓云鹏 杨洁[2] 罗闽 孙艺璇 李思远 徐文娟 董玲 ZHU Yu-xin;QI Yun-peng;YANG Jie;LUO Min;SUN Yi-xuan;LI Si-yuan;XU Wen-juan;DONG Ling(School of Life Sciences,Beijing University of Chinese Medicine,Beijing 100029,China;School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]北京中医药大学生命科学学院,北京100029 [2]北京中医药大学中药学院,北京100029

出　　处：《中国中药杂志》2024年第21期5877-5887,共11页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(82003943)。

摘　　要：基于鲜参及其炮制品对心肌缺血小鼠保护作用药效差异,明确鲜参优势作用环节,并利用网络药理学结合细胞模型验证,初步揭示鲜参调控FoxO信号通路的分子机制。采用腹腔注射盐酸异丙肾上腺素(ISO)制备小鼠心肌缺血模型,比较鲜参及其炮制品对心肌缺血的保护作用,鲜参在抗脂质过氧化减轻小鼠心肌缺血方面更具有优势。以此为基础开展网络药理学研究,结果表明鲜参含有19个优势活性成分及38个关键靶点,包括白蛋白(ALB)、丝氨酸/苏氨酸蛋白激酶(AKT1)、表皮生长因子受体(EGFR)、细胞外调节蛋白激酶(ERK1/2)、丝裂原活化蛋白激酶(P38)等。鲜参可通过Ras、FoxO、IL-17、Rap1等信号通路调节机体的细胞增殖和凋亡、炎症反应、氧化应激反应等多种生物功能,进而达到保护心肌细胞的作用。其中FoxO信号通路为鲜参的特征通路,进一步发现人参皂苷Re、人参皂苷Rg_(1)、β-榄香烯等鲜参优势活性成分可以通过AKT、JNK、EGFR、P38等靶点调控此通路。生物学验证结果表明人参皂苷Re、人参皂苷Rg_(1)、β-榄香烯能增强细胞生存活力、降低细胞上清液中乳酸脱氢酶(LDH)含量及活性氧(ROS)水平。靶点验证结果表明人参皂苷Rg_(1)、β-榄香烯能显著下调FoxO信号通路中EGFR蛋白表达,人参皂苷Re、β-榄香烯能显著下调ERK1/2、P38表达。该研究揭示了鲜参对心肌缺血保护作用的优势环节,为鲜参及相关产品的深度开发提供了一定的理论依据。Based on the differences in the protective effects of fresh Panax ginseng and its processed products on myocardial ischemia in mice,this study identified the advantageous aspects of fresh P.ginseng.By using network pharmacology combined with cell model validation,the molecular mechanisms of fresh P.ginseng in regulating the FoxO signaling pathway were preliminarily revealed.A mouse model of myocardial ischemia was established via intraperitoneal injection of isoproterenol hydrochloride(ISO).The comparison of the protective effects of fresh P.ginseng and its processed products on myocardial ischemia indicated that fresh P.ginseng had a more pronounced effect in reducing lipid peroxidation and alleviating myocardial ischemia in mice.On this basis,network pharmacology research was conducted,showing that fresh P.ginseng contained 19 dominant active ingredients and 38 key targets,including albumin(ALB),serine/threonine protein kinase(AKT1),epidermal growth factor receptor(EGFR),extracellular signal-regulated kinases(ERK1/2),and mitogen-activated protein kinase(P38).Fresh P.ginseng could regulate various biological functions such as cell proliferation,apoptosis,inflammation,and oxidative stress through signaling pathways including Ras,FoxO,IL-17,and Rap1,thereby protecting cardiomyocytes.Among them,the FoxO signaling pathway was identified as a characteristic pathway for fresh P.ginseng.It was further discovered that the dominant active components of fresh P.ginseng,such as ginsenoside Re,ginsenoside Rg_(1),andβ-elemene,could regulate this pathway through targets such as AKT,JNK,EGFR,and P38.Biological validation results showed that ginsenoside Re,ginsenoside Rg_(1),andβ-elemene could enhance cell viability,reduce lactate dehydrogenase(LDH)content,and decrease reactive oxygen species(ROS)levels in the cell supernatant.Target validation results indicated that ginsenoside Rg_(1)andβ-elemene significantly down-regulated the expression of EGFR protein in the FoxO signaling pathway,while ginsenoside Re andβ-elemene sign

关 键 词：鲜参 心肌缺血 网络药理学 FoxO信号通路 分子机制 

分 类 号：R285.5[医药卫生—中药学]