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Four Citrus Flavanones Exert Atherosclerosis Alleviation Effects in ApoE-/- Mice via Different Metabolic and Signaling Pathways

文献类型： 外文期刊

作者： Wang Feng;Zhao Chengying;Yang Minke;Zhang Lin;Wei Rujun;Meng Kun;Bao Yuming;Zhang Lina;Zheng Jinkai

作者机构：

关键词： atherosclerosis alleviation; citrus flavanones; gut microbiota; in vivo metabolism; signaling pathway

期刊名称： Journal of agricultural and food chemistry

ISSN： 1520-5118

年卷期： 2021 年 69 卷 17 期

页码：

收录情况： JCR（2021版） ; EI（2021版）

摘要： Citrus flavanones have the potential to alleviate atherosclerosis. The metabolism and anti-atherosclerosis signaling pathways of four citrus flavanones (naringin, naringenin, hesperidin, and hesperetin) were compared in ApoE-/- mice. Naringin had the most potent anti-atherogenic effect, followed by hesperidin, naringenin, and hesperetin with reductions of 55.92, 34.98, 42.87, and 24.70% in the atherosclerotic plaque rate compared with the control, respectively. Oral naringin mainly existed in the intestine due to the high water solubility of 7-O-nohesperidoside and alleviated atherosclerosis mainly by enhancing bile acid synthesis in the gut microbiota-FXR/FGF15-CYP7A1 pathway. The other three flavanones mainly alleviated atherosclerosis in the liver after absorption from the intestine. Hesperidin upregulates ABCA1 by 1.8-fold to enhance cholesterol reverse transport, while the aglycones naringenin and hesperetin inhibited cholesterol synthesis via downregulating HMGCR by 2.4- and 2.3-fold, respectively. Hesperetin was more resistant to absorption than naringenin due to the existence of a 4'-methoxyl group and had relatively weak effects on atherosclerosis. The alleviation of atherosclerosis by the four citrus flavanones was tightly related to differences in their in vivo metabolism and signaling pathways. This provides new insights into the anti-atherosclerotic mechanisms of food functional flavanones and guidance for the design of novel, efficient strategies for preventing atherosclerosis based on citrus flavanones.

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