title: Berberine protects against palmitate-induced endothelial dysfunction: involvements of upregulation of AMPK and eNOS and downregulation of NOX4.
abstract: 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.
authors.affiliation: Key Laboratory of Pathobiology, Department of Pharmacology, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Pharmaceutical College of Beihua University, Jilin City, Jilin 132013, China.
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Wang
authors.affiliation: Key Laboratory of Pathobiology, Department of Pharmacology, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Pathobiology, Department of Pharmacology, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, China.
authors.forename: Zhao-Jie
authors.initials: ZJ
authors.lastname: Meng
authors.affiliation: Key Laboratory of Pathobiology, Department of Pharmacology, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, China.
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Wei
authors.affiliation: Key Laboratory of Pathobiology, Department of Pharmacology, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520-8056, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Bucala
authors.affiliation: Key Laboratory of Pathobiology, Department of Pharmacology, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, China.
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Li
authors.affiliation: Key Laboratory of Pathobiology, Department of Pharmacology, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000502:physiology*; D001599:Berberine / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000502:physiology*; D019308:Palmitic Acid / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D001599:Berberine; D019308:Palmitic Acid; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases