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

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...

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Autores principales: Lu, Zheng, Liu, Lu, Zhao, Shunxin, Zhao, Jiangtao, Li, Sujun, Li, Mingyang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10192453/
https://www.ncbi.nlm.nih.gov/pubmed/37198205
http://dx.doi.org/10.1038/s41598-023-34654-2
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author Lu, Zheng
Liu, Lu
Zhao, Shunxin
Zhao, Jiangtao
Li, Sujun
Li, Mingyang
author_facet Lu, Zheng
Liu, Lu
Zhao, Shunxin
Zhao, Jiangtao
Li, Sujun
Li, Mingyang
author_sort Lu, Zheng
collection PubMed
description 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 pubmed-101924532023-05-19 Apigenin attenuates atherosclerosis and non-alcoholic fatty liver disease through inhibition of NLRP3 inflammasome in mice Lu, Zheng Liu, Lu Zhao, Shunxin Zhao, Jiangtao Li, Sujun Li, Mingyang Sci Rep Article 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. Nature Publishing Group UK 2023-05-17 /pmc/articles/PMC10192453/ /pubmed/37198205 http://dx.doi.org/10.1038/s41598-023-34654-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Lu, Zheng
Liu, Lu
Zhao, Shunxin
Zhao, Jiangtao
Li, Sujun
Li, Mingyang
Apigenin attenuates atherosclerosis and non-alcoholic fatty liver disease through inhibition of NLRP3 inflammasome in mice
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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10192453/
https://www.ncbi.nlm.nih.gov/pubmed/37198205
http://dx.doi.org/10.1038/s41598-023-34654-2
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