基于网络药理学探讨银杏叶提取物通过激活PPARγ治疗动脉粥样硬化的机制  

Network pharmacology-based study of the mechanism of Ginkgo biloba extract(GBE)in the treatment of atherosclerosis by activating PPARγ

作　　者：王子元 陶惠 肖映雪 殷志琦 WANG Ziyuan;TAO Hui;XIAO Yingxue;YIN Zhiqi(Department of TCMs Pharmaceuticals,School of Traditional Chinese Pharmacy,China Pharmaceutical University,Nanjing 211198;Department of Natural Medicinal Chemistry,School of Traditional Chinese Pharmacy,China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]中国药科大学中药学院中药制药系,南京211198 [2]中国药科大学中药学院天然药物化学系,南京211198

出　　处：《中国药科大学学报》2025年第2期225-235,共11页Journal of China Pharmaceutical University

摘　　要：探讨银杏叶提取物(Ginkgo biloba extract,GBE)对高脂饮食诱导的ApoE-/-小鼠动脉粥样硬化疾病(atherosclerosis,AS)的影响和作用机制。ApoE-/-小鼠灌胃给予低、高剂量GBE[50、150 mg/(kg·d)],9周后检测小鼠血脂水平,主动脉斑块脂质沉积情况、坏死核心面积和血管炎症水平。利用TCMSP、Swiss Target Prediction、Genecards等公共数据库预测GBE治疗AS的潜在靶点,通过GO和KEGG富集分析寻找其药效发挥的可能机制。在细胞水平上,氧化低密度脂蛋白(oxidized low density lipoprotein,oxLDL)处理THP-1形成泡沫细胞进行实验,使用油红O染色检测脂质蓄积情况,Dil-oxLDL检测泡沫细胞生成,使用RT-qPCR检测胆固醇摄取和外排受体的mRNA变化情况。最后,使用Western blot、免疫荧光等检测GBE对核心靶点过氧化物酶体增殖物激活受体γ(peroxisome proliferators-activated receptors-γ,PPARγ)表达情况的影响。结果显示,GBE可以减少小鼠主动脉脂质沉积和坏死核心面积,降低血清脂质和炎症水平。在体外减少巨噬细胞胆固醇摄取、增加胆固醇外排。本研究表明,GBE可以通过增强PPARγ的表达减少泡沫细胞的生成,抑制主动脉胆固醇蓄积和斑块的形成,缓解AS。To investigate the effect of Ginkgo biloba extract(GBE)on lipids accumulation and the progression of atherosclerosis(AS),ApoE^(-/-)mice fed with HFD were injected i.g.with two different doses of GBE(GBE-L 50 mg/(kg·d)or GBE-H 150 mg/(kg·d))for 9 weeks.The core targets and potential mechanisms of GBE therapy for AS were investigated using network pharmacological target prediction.Subsequently,oxidized low-density lipoprotein(ox-LDL)-induced THP-1 was used to investigate the effect of GBE on foam cell formation through oil red staining and Dil-oxLDL fluorescent staining.The mRNA alterations in cholesterol uptake and efflux receptors were detected by real-time quantitative PCR.Finally,the impact of GBE on the expression of PPARγas the core target was assessed through Western blot and immunofluorescence.It was found that GBE improved serum lipid profile,reduced necrotic cores and lipid deposition in aortic root plaques,and decreased the level of inflammatory factors in serum of ApoE^(-/-)mice.Moreover,GBE treatment reduced the level of intracellular lipid accumulation and inhibited cholesterol uptake and efflux to alleviate foam cell formation.GBE activated PPARγ to enhance ABCA1/ABCG1-induced cholesterol efflux in THP-1.These results suggest that GBE can suppress lipid accumulation and alleviate foam cell formation by activating PPARγ pathway.

关 键 词：银杏叶提取物 动脉粥样硬化 泡沫细胞 PPARΓ 

分 类 号：R965[医药卫生—药理学]