Berberine Protects against Palmitate-Induced Endothelial Dysfunction: Involvements of Upregulation of AMPK and eNOS and Downregulation of NOX4

Endothelial dysfunction is a critical factor during the initiation of cardiovascular complications in diabetes. Berberine can ameliorate endothelial dysfunction induced by diabetes. However, the underlying mechanisms remain unclear. The aim of this study was to investigate the protective effect and...

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Main Authors: Ming Zhang, Chun-Mei Wang, Jing Li, Zhao-Jie Meng, Sheng-Nan Wei, Ji Li, Richard Bucala, Yu-Lin Li, Li Chen
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2013/260464
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author Ming Zhang
Chun-Mei Wang
Jing Li
Zhao-Jie Meng
Sheng-Nan Wei
Ji Li
Richard Bucala
Yu-Lin Li
Li Chen
author_facet Ming Zhang
Chun-Mei Wang
Jing Li
Zhao-Jie Meng
Sheng-Nan Wei
Ji Li
Richard Bucala
Yu-Lin Li
Li Chen
author_sort Ming Zhang
collection DOAJ
description Endothelial dysfunction is a critical factor during the initiation of cardiovascular complications in diabetes. Berberine can ameliorate endothelial dysfunction induced by diabetes. However, the underlying mechanisms remain unclear. The aim of this study was to investigate the protective effect and mechanism of berberine on palmitate-induced endothelial dysfunction in human umbilical vein endothelial cells (HUVECs). The cell viability of HUVECs was determined by MTT assays. Nitric oxide (NO) level and production of reactive oxygen species (ROS) were determined in supernatants or in the cultured HUVECs. The mRNA level of endothelial nitric oxide synthase (eNOS) was measured by RT-PCR, and the protein levels of eNOS, p-eNOS, Akt, p-Akt, AMPK, p-AMPK, and NADPH oxidase (NOX4) were analyzed. The results demonstrated that berberine significantly elevated NO levels and reduced the production of ROS. The expressions of eNOS were significantly increased, while NOX4 protein expression was decreased in berberine-treated HUVECs. Moreover, berberine upregulated the protein expression of AMPK and p-AMPK in palmitate-treated HUVECs, but had no effect on the levels of Akt. Therefore, berberine ameliorates palmitate-induced endothelial dysfunction by upregulating eNOS expression and downregulating expression of NOX4. This regulatory effect of berberine may be related to the activation of AMPK.
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spelling doaj-art-96c1c9f76c7440e8a46d48423bbdfd5a2025-02-03T01:33:02ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/260464260464Berberine Protects against Palmitate-Induced Endothelial Dysfunction: Involvements of Upregulation of AMPK and eNOS and Downregulation of NOX4Ming Zhang0Chun-Mei Wang1Jing Li2Zhao-Jie Meng3Sheng-Nan Wei4Ji Li5Richard Bucala6Yu-Lin Li7Li Chen8Key Laboratory of Pathobiology, Department of Pharmacology, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, ChinaDepartment of Pharmacology, Pharmaceutical College of Beihua University, Jilin City, Jilin 132013, ChinaKey Laboratory of Pathobiology, Department of Pharmacology, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, ChinaKey Laboratory of Pathobiology, Department of Pharmacology, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, ChinaKey Laboratory of Pathobiology, Department of Pharmacology, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, ChinaKey Laboratory of Pathobiology, Department of Pharmacology, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, ChinaDepartment of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520-8056, USAKey Laboratory of Pathobiology, Department of Pharmacology, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, ChinaKey Laboratory of Pathobiology, Department of Pharmacology, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, ChinaEndothelial dysfunction is a critical factor during the initiation of cardiovascular complications in diabetes. Berberine can ameliorate endothelial dysfunction induced by diabetes. However, the underlying mechanisms remain unclear. The aim of this study was to investigate the protective effect and mechanism of berberine on palmitate-induced endothelial dysfunction in human umbilical vein endothelial cells (HUVECs). The cell viability of HUVECs was determined by MTT assays. Nitric oxide (NO) level and production of reactive oxygen species (ROS) were determined in supernatants or in the cultured HUVECs. The mRNA level of endothelial nitric oxide synthase (eNOS) was measured by RT-PCR, and the protein levels of eNOS, p-eNOS, Akt, p-Akt, AMPK, p-AMPK, and NADPH oxidase (NOX4) were analyzed. The results demonstrated that berberine significantly elevated NO levels and reduced the production of ROS. The expressions of eNOS were significantly increased, while NOX4 protein expression was decreased in berberine-treated HUVECs. Moreover, berberine upregulated the protein expression of AMPK and p-AMPK in palmitate-treated HUVECs, but had no effect on the levels of Akt. Therefore, berberine ameliorates palmitate-induced endothelial dysfunction by upregulating eNOS expression and downregulating expression of NOX4. This regulatory effect of berberine may be related to the activation of AMPK.http://dx.doi.org/10.1155/2013/260464
spellingShingle Ming Zhang
Chun-Mei Wang
Jing Li
Zhao-Jie Meng
Sheng-Nan Wei
Ji Li
Richard Bucala
Yu-Lin Li
Li Chen
Berberine Protects against Palmitate-Induced Endothelial Dysfunction: Involvements of Upregulation of AMPK and eNOS and Downregulation of NOX4
Mediators of Inflammation
title Berberine Protects against Palmitate-Induced Endothelial Dysfunction: Involvements of Upregulation of AMPK and eNOS and Downregulation of NOX4
title_full Berberine Protects against Palmitate-Induced Endothelial Dysfunction: Involvements of Upregulation of AMPK and eNOS and Downregulation of NOX4
title_fullStr Berberine Protects against Palmitate-Induced Endothelial Dysfunction: Involvements of Upregulation of AMPK and eNOS and Downregulation of NOX4
title_full_unstemmed Berberine Protects against Palmitate-Induced Endothelial Dysfunction: Involvements of Upregulation of AMPK and eNOS and Downregulation of NOX4
title_short Berberine Protects against Palmitate-Induced Endothelial Dysfunction: Involvements of Upregulation of AMPK and eNOS and Downregulation of NOX4
title_sort berberine protects against palmitate induced endothelial dysfunction involvements of upregulation of ampk and enos and downregulation of nox4
url http://dx.doi.org/10.1155/2013/260464
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