滁菊总黄酮对高胆固醇血症的改善作用及机制

Improvement Effect and Mechanism of Total Flavonoids of Chuju on Hypercholesterolemia

目的:探究滁菊总黄酮对小鼠高脂饮食所致高胆固醇血症的改善作用,并通过网络药理学初步分析其作用机制。方法:采用高脂饲料构建小鼠高胆固醇血症模型,按照低、中、高(50、100、200 mg/kg)剂量分别灌胃给药,同时设置正常对照组、水飞蓟组及模型组。实验结束后检测相关血液生化指标,并取肝脏进行病理学检查,根据实验结果结合网络药理学实验初步筛选滁菊总黄酮改善高胆固醇血症的关键靶点及通路,预测其可能的作用机制。结果:高剂量给药组(200 mg/kg)与模型组相比,总胆固醇(Total cholesterol,TC)、低密度脂蛋白胆固醇(Low density lipoprotein cholesterol,LDL-C)及丙二醛(Malondialdehyde,MDA)水平显著下降,谷丙转氨酶(Alanine transaminase,ALT)、谷草转氨酶(Aspartate aminotransferase,AST)活性显著降低,超氧化物歧化酶(Total superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(Glutathione peroxidase,GSH-Px)活性显著增高(P<0.05)。肝组织病理切片显示,与模型组相比,给药组小鼠肝细胞空泡水肿、炎性细胞浸润情况和脂滴明显减少。通过网络药理学从滁菊总黄酮中共筛选出异泽兰黄素、金合欢素等13个关键活性成分,以及AKT1、GAPDH、TNF等50个关键靶点,推测滁菊总黄酮可能通过PI3K-AKT信号通路、内分泌抵抗通路等改善高胆固醇血症。结论:滁菊总黄酮对高脂饲料所致小鼠高胆固醇血症具有一定的改善作用,其作用机制可能是13种关键成分作用于50个关键靶点上,通过PI3K-AKT信号通路等关键通路,起到抗氧化和减少脂质过氧化物产生的作用,从而避免了胆固醇在体内的过度蓄积。

Objective:To investigate the improvement effect of total flavonoids of Chuju(Chrysanthemum morifolium)on hypercholesterolemia induced by a high-fat diet in mice and explore its mechanism through network pharmacology.Methods:A well-established mouse model of hypercholesterolemia was established using a high-fat diet,administered intragastrically at low,medium or high(50,100,200 mg/kg)doses,together with normal control group,milk thistle group and model group.After completing the feeding interventions,appropriately related blood biochemical indexes were analyzed,and the liver was harvested for pathological examination.The results of these investigations were combined with network pharmacological experiments,and key targets and pathways of total flavonoids of Chuju in improving hypercholesterolemia were preliminarily screened,and its possible mechanism was predicted.Results:Compared with the model group,the levels of TC,LDL-C and MDA decreased significantly,ALT and AST activities decreased significantly,and the activities of SOD and GSH-Px increased significantly in the high dose administration group(P<0.05).Pathological sections of liver tissue showed that compared with the model group,the vacuolar edema,inflammatory cell infiltration and lipid droplets of hepatocytes in the administration group were significantly reduced.Through network pharmacology,13 key active components such as isoprenin and acacetin and 50 key targets such as AKT1,GAPDH,TNF were screened from the total flavonoids of Chuju.Ultimately,it was postulated that the total flavonoids of Chuju might improve hypercholesterolemia through the PI3K-AKT signaling pathway and endocrine resistance pathway.Conclusion:Total flavonoids of Chuju improved hypercholesterolemia induced by a high-fat diet in mice.The mechanism of action appeared to involve 13 key components acting on 50 targets,which played an antioxidant role and reduced lipid peroxide production through key pathways such as the PI3K-AKT signaling pathway.The final result was prevention of excessive cholesterol accumulation in vivo.