Zhang Runlei, Wu Shengxian, Ye Chao, Li Pengyang, Xu Bing, Wang Yue, Yang Zheng, Chen Xinyi, Chen Jing
Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
Orthopedics Department, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
J Nutr Biochem. 2025 May;139:109866. doi: 10.1016/j.jnutbio.2025.109866. Epub 2025 Feb 13.
Naringin, a flavonoid, has high antioxidant activity and hypolipidemic pharmacological effects. In this study, an animal model of dyslipidemia was established by feeding Apoe mice a high-fat diet for 4 weeks. Subsequently, the mice were administered Naringin via gavage at doses of 50 mg/(kg·d), 100 mg/(kg·d), or 200 mg/(kg·d) for an additional 4 weeks. The research utilized liquid chromatography-mass spectrometry (LC-MS) metabolomics in conjunction with analyses of serum oxidative stress markers, Hematoxylin-eosin staining, Masson's trichome staining, and immunohistochemical staining. Naringin treatment reduced serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol concentrations (P<.05), reversed disorders of vascular structure and morphology, increased serum nicotinamide adenine dinucleotide phosphate hydride and glutathione concentrations (P<.05), reduced serum peroxynitrite concentrations (P<.05), promoted aortic endothelial nitric oxide synthase protein expression and inhibited aortic prolyl isomerase-1 protein expression. Twenty differentiated metabolites were obtained from the serum by LC-MS assay, followed by 16 differential metabolic pathways after enrichment. Among the metabolic pathways, glycolysis/gluconeogenesis, the pentose phosphate pathway, purine metabolism, ascorbate metabolism, and aldarate metabolism are the most relevant metabolic pathways by which naringin reduces oxidative stress. Our findings suggest that naringin can reduce oxidative stress levels associated with dyslipidemia through multiple metabolic pathways, protect vascular endothelial function, and thus providing a novel and promising natural medicine for treating dyslipidemia.
柚皮苷是一种黄酮类化合物，具有较高的抗氧化活性和降血脂药理作用。在本研究中，通过给载脂蛋白E（Apoe）小鼠喂食高脂饮食4周建立血脂异常动物模型。随后，小鼠通过灌胃给予剂量为50毫克/（千克·天）、100毫克/（千克·天）或200毫克/（千克·天）的柚皮苷，持续另外4周。该研究利用液相色谱 - 质谱联用（LC - MS）代谢组学技术，结合血清氧化应激标志物分析、苏木精 - 伊红染色、马松三色染色和免疫组织化学染色。柚皮苷治疗降低了血清总胆固醇、甘油三酯和低密度脂蛋白胆固醇浓度（P<0.05），逆转了血管结构和形态的紊乱，增加了血清烟酰胺腺嘌呤二核苷酸磷酸氢化物和谷胱甘肽浓度（P<0.05），降低了血清过氧亚硝酸盐浓度（P<0.05），促进了主动脉内皮型一氧化氮合酶蛋白表达并抑制了主动脉脯氨酰异构酶 - 1蛋白表达。通过LC - MS分析从血清中获得了20种差异代谢物，富集后有16条差异代谢途径。在这些代谢途径中，糖酵解/糖异生、磷酸戊糖途径、嘌呤代谢、抗坏血酸代谢和醛糖代谢是柚皮苷降低氧化应激最相关的代谢途径。我们的研究结果表明，柚皮苷可通过多种代谢途径降低与血脂异常相关的氧化应激水平，保护血管内皮功能，从而为治疗血脂异常提供一种新型且有前景的天然药物。
