Apigenin attenuates atherosclerosis and non-alcoholic fatty liver disease through inhibition of NLRP3 inflammasome in mice

Abstract Apigenin (APN), a flavone found in several plant foods with various biological properties such as anti-obesity, anti-inflammation and other abilities, alleviates atherosclerosis and non-alcoholic fatty liver disease (NAFLD) induced by a high fat diet (HFD) in mice. However, the underlying m...

Ամբողջական նկարագրություն

Մատենագիտական մանրամասներ
Հիմնական հեղինակներ: Zheng Lu, Lu Liu, Shunxin Zhao, Jiangtao Zhao, Sujun Li, Mingyang Li
Ձևաչափ: Հոդված
Լեզու:English
Հրապարակվել է: Nature Portfolio 2023-05-01
Շարք:Scientific Reports
Առցանց հասանելիություն:https://doi.org/10.1038/s41598-023-34654-2
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author Zheng Lu
Lu Liu
Shunxin Zhao
Jiangtao Zhao
Sujun Li
Mingyang Li
author_facet Zheng Lu
Lu Liu
Shunxin Zhao
Jiangtao Zhao
Sujun Li
Mingyang Li
author_sort Zheng Lu
collection DOAJ
description Abstract Apigenin (APN), a flavone found in several plant foods with various biological properties such as anti-obesity, anti-inflammation and other abilities, alleviates atherosclerosis and non-alcoholic fatty liver disease (NAFLD) induced by a high fat diet (HFD) in mice. However, the underlying mechanisms have not been fully understood. In this study, we investigated the role of NLRP3 in anti-atherosclerosis and anti-NAFLD effect of APN in mouse models with NLRP3 deficiency. Atherosclerosis and NAFLD models were established by treatment of low density lipoprotein receptor-deficient (Ldlr −/− ) mice and NLRP3 −/− Ldlr −/− mice with a HFD diet (20% fat and 0.5% cholesterol) with or without APN. En face lipid accumulation analysis, plasma lipid levels, hepatic lipid accumulation and inflammation were analyzed and quantified. For in vitro experiments, HepG2 cells were stimulated by LPS plus oleic acid (OA) in the absence or presence of APN (50 μM). Lipid accumulation and the effect of APN on the NLRP3/NF-κB signaling pathway were investigated. APN administration partly reversed atherosclerosis and hepatic lipid accumulation, and decreased body weight and plasma lipid levels in Ldlr −/− mice when fed a HFD. Compared with Ldlr −/− mice, NLRP3 −/− Ldlr −/− mice showed more severe atherosclerosis and hepatic lipid accumulation. Treating the HepG2 cells with APN reduced lipid accumulation. APN also inhibited activation of the NLRP3/ NF-κB signaling pathway stimulated by OA together with LPS. Our results indicate that APN supplementation prevents atherosclerosis and NAFLD via NLRP3 inhibition in mice, and suggest that APN might be a potential therapeutic agent for the prevention of atherosclerosis and NAFLD.
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spelling doaj.art-7a1567e89d9543fe9843e72654015ebd2023-05-21T11:12:44ZengNature PortfolioScientific Reports2045-23222023-05-0113111110.1038/s41598-023-34654-2Apigenin attenuates atherosclerosis and non-alcoholic fatty liver disease through inhibition of NLRP3 inflammasome in miceZheng Lu0Lu Liu1Shunxin Zhao2Jiangtao Zhao3Sujun Li4Mingyang Li5Medical Department of Henan Provincial People’s HospitalDepartment of Nephrology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Cardiology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Geriatric Endocrinology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Emergency, Henan Provincial People’s HospitalAbstract Apigenin (APN), a flavone found in several plant foods with various biological properties such as anti-obesity, anti-inflammation and other abilities, alleviates atherosclerosis and non-alcoholic fatty liver disease (NAFLD) induced by a high fat diet (HFD) in mice. However, the underlying mechanisms have not been fully understood. In this study, we investigated the role of NLRP3 in anti-atherosclerosis and anti-NAFLD effect of APN in mouse models with NLRP3 deficiency. Atherosclerosis and NAFLD models were established by treatment of low density lipoprotein receptor-deficient (Ldlr −/− ) mice and NLRP3 −/− Ldlr −/− mice with a HFD diet (20% fat and 0.5% cholesterol) with or without APN. En face lipid accumulation analysis, plasma lipid levels, hepatic lipid accumulation and inflammation were analyzed and quantified. For in vitro experiments, HepG2 cells were stimulated by LPS plus oleic acid (OA) in the absence or presence of APN (50 μM). Lipid accumulation and the effect of APN on the NLRP3/NF-κB signaling pathway were investigated. APN administration partly reversed atherosclerosis and hepatic lipid accumulation, and decreased body weight and plasma lipid levels in Ldlr −/− mice when fed a HFD. Compared with Ldlr −/− mice, NLRP3 −/− Ldlr −/− mice showed more severe atherosclerosis and hepatic lipid accumulation. Treating the HepG2 cells with APN reduced lipid accumulation. APN also inhibited activation of the NLRP3/ NF-κB signaling pathway stimulated by OA together with LPS. Our results indicate that APN supplementation prevents atherosclerosis and NAFLD via NLRP3 inhibition in mice, and suggest that APN might be a potential therapeutic agent for the prevention of atherosclerosis and NAFLD.https://doi.org/10.1038/s41598-023-34654-2
spellingShingle Zheng Lu
Lu Liu
Shunxin Zhao
Jiangtao Zhao
Sujun Li
Mingyang Li
Apigenin attenuates atherosclerosis and non-alcoholic fatty liver disease through inhibition of NLRP3 inflammasome in mice
Scientific Reports
title Apigenin attenuates atherosclerosis and non-alcoholic fatty liver disease through inhibition of NLRP3 inflammasome in mice
title_full Apigenin attenuates atherosclerosis and non-alcoholic fatty liver disease through inhibition of NLRP3 inflammasome in mice
title_fullStr Apigenin attenuates atherosclerosis and non-alcoholic fatty liver disease through inhibition of NLRP3 inflammasome in mice
title_full_unstemmed Apigenin attenuates atherosclerosis and non-alcoholic fatty liver disease through inhibition of NLRP3 inflammasome in mice
title_short Apigenin attenuates atherosclerosis and non-alcoholic fatty liver disease through inhibition of NLRP3 inflammasome in mice
title_sort apigenin attenuates atherosclerosis and non alcoholic fatty liver disease through inhibition of nlrp3 inflammasome in mice
url https://doi.org/10.1038/s41598-023-34654-2
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