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Diosmetin Protects against Cardiac Hypertrophy via p62/Keap1/Nrf2 Signaling Pathway

An important pathophysiological consequence of pressure overload-induced cardiac hypertrophy is adverse cardiac remodeling, including structural changes in cardiomyocytes and extracellular matrix. Diosmetin (DIO), a monomethoxyflavone isolated from citrus fruits, had antioxidative stress effects in...

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Autores principales: Guo, Yingying, Li, Dan, Cen, Xian-feng, Qiu, Hong-liang, Ma, Yu-lan, Liu, Yi, Huang, Si-hui, Liu, Li-bo, Xu, Man, Tang, Qi-Zhu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8888112/
https://www.ncbi.nlm.nih.gov/pubmed/35242278
http://dx.doi.org/10.1155/2022/8367997
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author Guo, Yingying
Li, Dan
Cen, Xian-feng
Qiu, Hong-liang
Ma, Yu-lan
Liu, Yi
Huang, Si-hui
Liu, Li-bo
Xu, Man
Tang, Qi-Zhu
author_facet Guo, Yingying
Li, Dan
Cen, Xian-feng
Qiu, Hong-liang
Ma, Yu-lan
Liu, Yi
Huang, Si-hui
Liu, Li-bo
Xu, Man
Tang, Qi-Zhu
author_sort Guo, Yingying
collection PubMed
description An important pathophysiological consequence of pressure overload-induced cardiac hypertrophy is adverse cardiac remodeling, including structural changes in cardiomyocytes and extracellular matrix. Diosmetin (DIO), a monomethoxyflavone isolated from citrus fruits, had antioxidative stress effects in multiple organs. The purpose of this study was to examine the biological effect of diosmetin on pathological cardiac hypertrophy. In mice, diosmetin treatment reduced cardiac hypertrophy and dysfunction in an aortic banding- (AB-) induced pressure overload model and reducing myocardial oxidative stress by increasing antioxidant gene expression. In vitro, diosmetin (10 or 50 μm, 12 h or 24 h) protected PE-induced cardiomyocyte hypertrophy in neonatal rat cardiomyocytes. Mechanistically, diosmetin inhibited autophagy by activating the PI3K/Akt pathway. In particular, diosmetin induced the accumulation of p62 and its interaction with Keap1, promoted the nuclear translocation of Nrf2, and increased the expression of antioxidant stress genes in the process of cardiac hypertrophy. Furthermore, knockdown of p62 in rat primary cardiomyocytes abrogate the protective effect of diosmetin on cardiomyocyte hypertrophy. Similarly, the Nrf2 inhibitor ML385 obviously abolished the above effects by diosmetin treatment. In conclusion, our results suggest that diosmetin protects cardiac hypertrophy under pressure overload through the p62/Keap1/Nrf2 signaling pathway, suggesting the potential of diosmetin as a novel therapy for pathological cardiac hypertrophy.
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spelling pubmed-88881122022-03-02 Diosmetin Protects against Cardiac Hypertrophy via p62/Keap1/Nrf2 Signaling Pathway Guo, Yingying Li, Dan Cen, Xian-feng Qiu, Hong-liang Ma, Yu-lan Liu, Yi Huang, Si-hui Liu, Li-bo Xu, Man Tang, Qi-Zhu Oxid Med Cell Longev Research Article An important pathophysiological consequence of pressure overload-induced cardiac hypertrophy is adverse cardiac remodeling, including structural changes in cardiomyocytes and extracellular matrix. Diosmetin (DIO), a monomethoxyflavone isolated from citrus fruits, had antioxidative stress effects in multiple organs. The purpose of this study was to examine the biological effect of diosmetin on pathological cardiac hypertrophy. In mice, diosmetin treatment reduced cardiac hypertrophy and dysfunction in an aortic banding- (AB-) induced pressure overload model and reducing myocardial oxidative stress by increasing antioxidant gene expression. In vitro, diosmetin (10 or 50 μm, 12 h or 24 h) protected PE-induced cardiomyocyte hypertrophy in neonatal rat cardiomyocytes. Mechanistically, diosmetin inhibited autophagy by activating the PI3K/Akt pathway. In particular, diosmetin induced the accumulation of p62 and its interaction with Keap1, promoted the nuclear translocation of Nrf2, and increased the expression of antioxidant stress genes in the process of cardiac hypertrophy. Furthermore, knockdown of p62 in rat primary cardiomyocytes abrogate the protective effect of diosmetin on cardiomyocyte hypertrophy. Similarly, the Nrf2 inhibitor ML385 obviously abolished the above effects by diosmetin treatment. In conclusion, our results suggest that diosmetin protects cardiac hypertrophy under pressure overload through the p62/Keap1/Nrf2 signaling pathway, suggesting the potential of diosmetin as a novel therapy for pathological cardiac hypertrophy. Hindawi 2022-02-22 /pmc/articles/PMC8888112/ /pubmed/35242278 http://dx.doi.org/10.1155/2022/8367997 Text en Copyright © 2022 Yingying Guo et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Guo, Yingying
Li, Dan
Cen, Xian-feng
Qiu, Hong-liang
Ma, Yu-lan
Liu, Yi
Huang, Si-hui
Liu, Li-bo
Xu, Man
Tang, Qi-Zhu
Diosmetin Protects against Cardiac Hypertrophy via p62/Keap1/Nrf2 Signaling Pathway
title Diosmetin Protects against Cardiac Hypertrophy via p62/Keap1/Nrf2 Signaling Pathway
title_full Diosmetin Protects against Cardiac Hypertrophy via p62/Keap1/Nrf2 Signaling Pathway
title_fullStr Diosmetin Protects against Cardiac Hypertrophy via p62/Keap1/Nrf2 Signaling Pathway
title_full_unstemmed Diosmetin Protects against Cardiac Hypertrophy via p62/Keap1/Nrf2 Signaling Pathway
title_short Diosmetin Protects against Cardiac Hypertrophy via p62/Keap1/Nrf2 Signaling Pathway
title_sort diosmetin protects against cardiac hypertrophy via p62/keap1/nrf2 signaling pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8888112/
https://www.ncbi.nlm.nih.gov/pubmed/35242278
http://dx.doi.org/10.1155/2022/8367997
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