Heat Shock Protein 70 Mediates the Protective Effect of Naringenin on High-Glucose-Induced Alterations of Endothelial Function

Endothelial dysfunction plays a pivotal role in the development and progression of diabetic vascular complications. Naringenin (Nar) is a flavanone bioactive isolated from citrus fruits known to have in vitro and in vivo antidiabetic properties. However, whether Nar affects endothelial function rema...

Full description

Saved in:
Bibliographic Details
Main Authors: Zhihan Zhang, Hui Liu, Xiang Hu, Yikang He, Lu Li, Xinyu Yang, Changhua Wang, Mingbai Hu, Shengxiang Tao
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:International Journal of Endocrinology
Online Access:http://dx.doi.org/10.1155/2022/7275765
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850224380600123392
author Zhihan Zhang
Hui Liu
Xiang Hu
Yikang He
Lu Li
Xinyu Yang
Changhua Wang
Mingbai Hu
Shengxiang Tao
author_facet Zhihan Zhang
Hui Liu
Xiang Hu
Yikang He
Lu Li
Xinyu Yang
Changhua Wang
Mingbai Hu
Shengxiang Tao
author_sort Zhihan Zhang
collection DOAJ
description Endothelial dysfunction plays a pivotal role in the development and progression of diabetic vascular complications. Naringenin (Nar) is a flavanone bioactive isolated from citrus fruits known to have in vitro and in vivo antidiabetic properties. However, whether Nar affects endothelial function remains unclear in diabetes or under high-glucose (HG) condition. Using an in vitro model of hyperglycemia in human umbilical vein endothelial cells (HUVECs), we found that Nar administration markedly attenuated HG-induced alterations of endothelial function, evidenced by the mitigation of oxidative stress and inflammation, the reduction of cell adhesion molecular expressions, and the improvement of insulin resistance. We also found that HG exposure significantly reduced the levels of intracellular heat shock protein 70 (iHSP70 or iHSPA1A) and the release of HSP70 from HUVECs. HSP70 depletion mimicked and clearly diminished the protective effects of Nar on HG-induced alterations of endothelial function. In addition, Nar treatment significantly enhanced iHSP70 protein levels through a transcription-dependent manner. These results demonstrated that Nar could protect HUVECs against HG-induced alterations of endothelial function through upregulating iHSP70 protein levels. These findings are also helpful in providing new therapeutic strategies that are promising in the clinical use of Nar for the treatment of diabetes and diabetic complications.
format Article
id doaj-art-4fdf2c842d1a4356a26a6fb0ac3cd6ed
institution OA Journals
issn 1687-8345
language English
publishDate 2022-01-01
publisher Wiley
record_format Article
series International Journal of Endocrinology
spelling doaj-art-4fdf2c842d1a4356a26a6fb0ac3cd6ed2025-08-20T02:05:38ZengWileyInternational Journal of Endocrinology1687-83452022-01-01202210.1155/2022/7275765Heat Shock Protein 70 Mediates the Protective Effect of Naringenin on High-Glucose-Induced Alterations of Endothelial FunctionZhihan Zhang0Hui Liu1Xiang Hu2Yikang He3Lu Li4Xinyu Yang5Changhua Wang6Mingbai Hu7Shengxiang Tao8Department of Orthopaedic Trauma and MicrosurgeryDepartment of Orthopaedic Trauma and MicrosurgeryDepartment of Orthopaedic Trauma and MicrosurgeryTongji Medical College Huazhong University of Science and TechnologyDepartment of Pathology and PathophysiologyDepartment of Pathology and PathophysiologyDepartment of Pathology and PathophysiologyDepartment of Breast and Thyroid SurgeryDepartment of Orthopaedic Trauma and MicrosurgeryEndothelial dysfunction plays a pivotal role in the development and progression of diabetic vascular complications. Naringenin (Nar) is a flavanone bioactive isolated from citrus fruits known to have in vitro and in vivo antidiabetic properties. However, whether Nar affects endothelial function remains unclear in diabetes or under high-glucose (HG) condition. Using an in vitro model of hyperglycemia in human umbilical vein endothelial cells (HUVECs), we found that Nar administration markedly attenuated HG-induced alterations of endothelial function, evidenced by the mitigation of oxidative stress and inflammation, the reduction of cell adhesion molecular expressions, and the improvement of insulin resistance. We also found that HG exposure significantly reduced the levels of intracellular heat shock protein 70 (iHSP70 or iHSPA1A) and the release of HSP70 from HUVECs. HSP70 depletion mimicked and clearly diminished the protective effects of Nar on HG-induced alterations of endothelial function. In addition, Nar treatment significantly enhanced iHSP70 protein levels through a transcription-dependent manner. These results demonstrated that Nar could protect HUVECs against HG-induced alterations of endothelial function through upregulating iHSP70 protein levels. These findings are also helpful in providing new therapeutic strategies that are promising in the clinical use of Nar for the treatment of diabetes and diabetic complications.http://dx.doi.org/10.1155/2022/7275765
spellingShingle Zhihan Zhang
Hui Liu
Xiang Hu
Yikang He
Lu Li
Xinyu Yang
Changhua Wang
Mingbai Hu
Shengxiang Tao
Heat Shock Protein 70 Mediates the Protective Effect of Naringenin on High-Glucose-Induced Alterations of Endothelial Function
International Journal of Endocrinology
title Heat Shock Protein 70 Mediates the Protective Effect of Naringenin on High-Glucose-Induced Alterations of Endothelial Function
title_full Heat Shock Protein 70 Mediates the Protective Effect of Naringenin on High-Glucose-Induced Alterations of Endothelial Function
title_fullStr Heat Shock Protein 70 Mediates the Protective Effect of Naringenin on High-Glucose-Induced Alterations of Endothelial Function
title_full_unstemmed Heat Shock Protein 70 Mediates the Protective Effect of Naringenin on High-Glucose-Induced Alterations of Endothelial Function
title_short Heat Shock Protein 70 Mediates the Protective Effect of Naringenin on High-Glucose-Induced Alterations of Endothelial Function
title_sort heat shock protein 70 mediates the protective effect of naringenin on high glucose induced alterations of endothelial function
url http://dx.doi.org/10.1155/2022/7275765
work_keys_str_mv AT zhihanzhang heatshockprotein70mediatestheprotectiveeffectofnaringeninonhighglucoseinducedalterationsofendothelialfunction
AT huiliu heatshockprotein70mediatestheprotectiveeffectofnaringeninonhighglucoseinducedalterationsofendothelialfunction
AT xianghu heatshockprotein70mediatestheprotectiveeffectofnaringeninonhighglucoseinducedalterationsofendothelialfunction
AT yikanghe heatshockprotein70mediatestheprotectiveeffectofnaringeninonhighglucoseinducedalterationsofendothelialfunction
AT luli heatshockprotein70mediatestheprotectiveeffectofnaringeninonhighglucoseinducedalterationsofendothelialfunction
AT xinyuyang heatshockprotein70mediatestheprotectiveeffectofnaringeninonhighglucoseinducedalterationsofendothelialfunction
AT changhuawang heatshockprotein70mediatestheprotectiveeffectofnaringeninonhighglucoseinducedalterationsofendothelialfunction
AT mingbaihu heatshockprotein70mediatestheprotectiveeffectofnaringeninonhighglucoseinducedalterationsofendothelialfunction
AT shengxiangtao heatshockprotein70mediatestheprotectiveeffectofnaringeninonhighglucoseinducedalterationsofendothelialfunction