摘要
目的:应用网络药理学和实验验证,分析沙棘叶治疗高脂血症的药效物质基础。方法:建立油酸-棕榈酸(摩尔比2∶1)诱导的HepG2高脂细胞模型,细胞增殖与活性检测法(CCK-8)确定沙棘叶含药血清的最适给药浓度,并利用沙棘叶含药血清对细胞进行干预,进行油红O染色确定其造模成功,应用酶联免疫吸附测定法(ELISA)测定细胞的总胆固醇(TG)和甘油三酯(TC)含量。应用网络药理学分析可能的作用机制;分子对接确定潜在作用靶点的作用能力。结果:CCK-8实验表明,10%含药血清浓度为细胞生长的最适浓度,油红O染色表明,经油酸-棕榈酸(摩尔比2∶1)诱导的高脂细胞模型已经形成;经含药血清处理后,细胞的总胆固醇(TG)、甘油三酯(TC)含量均下降,表明沙棘叶对高脂血症具有良好的治疗作用。网络药理学分析发现,沙棘叶治疗高脂血症的核心靶点为血清白蛋白(ALB)、过氧化物酶体增殖物激活受体γ(PPARγ)、基质金属蛋白酶-9(MMP-9)等,涉及755条生物过程,73条分子功能,3种细胞组成;京都基因与基因组百科全书(KEGG)分析表明沙棘叶治疗高脂血症涉及PPAR信号通路、缺氧诱导因子(HIF)-1信号通路、AMP活化蛋白激酶(AMPK)信号通路等多条通路。结论:10%沙棘叶含药血清可降低高脂细胞模型的脂质累积和降低细胞内的TG、TC水平。网络药理学研究表明其作用机制可能是通过激活PPAR信号通路等实现的。
Objective:To analyze the pharmacodynamic material basis of Hippophae Folium in the treatment of hyperlipidemia by network pharmacology and experimental verification.Method:The hyperlipidemic HepG2 cell model induced by oleic and palmitic acid(molar ratio 2∶1)was established.The optimal concentration of Hippophae Folium containing serum was determined by cell counting kit(CCK)-8 method.The cells were intervened by the medicated serum,and oil red O staining was used to determine the success of the model.The contents of total cholesterol(TC)and triglyceride(TG)were determined by enzymelinked immunosorbent assay(ELISA).The possible mechanism of action was analyzed by network pharmacology,and molecular docking was performed to detect the binding ability of the potential targets.Result:CCK-8 assay showed that 10%medicated serum was the optimal concentration for cell growth.Oil red O staining proved that the hyperlipidemic cell model induced by oleic and palmitic acid has been built.After treatment with medicated serum,the contents of TG and TC decreased,indicating that Hippophae Folium had a good therapeutic effect on hyperlipidemia.Network pharmacology revealed that the core targets of Hippophae Folium in the treatment of hyperlipidemia were albumin(ALB),peroxisome proliferative activated receptorγ(PPARγ)and matrix metalloprotein(MMP)-9,involving 755 biological processes,73 molecular functions and 3 cellular components.By Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis,it was found PPAR,hypoxia inducible factor(HIF)-1,AMP-activated protein kinase(AMPK)and other signal pathways were involved in the treatment of hyperlipidemia by Hippophae Folium.Conclusion:Hippophae Folium containing serum(10%)could reduce lipid accumulation and intracellular TG and TC levels in hyperlipidemic cell model,and its mechanism of action might be realized by activating PPAR signal pathway.
作者
唐瑜
张依娜
邹远荣
乔佳欣
刘思雨
高峰
TANG Yu;ZHANG Yina;ZOU Yuanrong;QIAO Jiaxin;LIU Siyu;GAO Feng(College of Pharmacy,Shaanxi University of Chinese Medicine,Xianyang 712046,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2022年第22期116-122,共7页
Chinese Journal of Experimental Traditional Medical Formulae
基金
陕西省中医药管理局项目(2021-02-ZZ-008)
咸阳市二〇二〇年重点研发计划项目(2020K02-96)
咸阳市科技局-基于沙棘果渣及叶废弃资源循环再利用的沙棘类产品的研究与开发项目(2019K02-121)
陕西省教育厅重点项目(20JC011)。
关键词
沙棘叶
高脂血症
作用机制
分子对接
Hippophae Folium
hyperlipidemia
mechanism of action
molecular docking
