1. Novel role of the nutraceutical bioactive compound berberine in lectin-like OxLDL receptor 1-mediated endothelial dysfunction in comparison to lovastatin
- Author
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Mara Mirasoli, Silvana Hrelia, Patrizia Simoni, Paola Rizzo, Emanuela Leoncini, Donato Calabria, Massimo Guardigli, Roberto Ferrari, Cristiana Caliceti, Aldo Roda, Giorgio Aquila, Laura Zambonin, Arrigo F G Cicero, Francesca Fortini, Benedetta Rizzo, Caliceti, Cristiana, Rizzo, P., Ferrari, R., Fortini, F., Aquila, G., Leoncini, Emanuela, Zambonin, Laura, Rizzo, Benedetta, Calabria, Donato, Simoni, P., Mirasoli, Mara, Guardigli, Massimo, Hrelia, Silvana, Roda, Aldo, and Cicero, Arrigo Francesco Giuseppe
- Subjects
0301 basic medicine ,MAPK/ERK pathway ,Berberine ,Endothelial dysfunction ,Lovastatin ,oxLDL ,oxLDL receptor-1 ,Reactive oxygen species ,Tumor necrosis factor ,Medicine (miscellaneous) ,Endocrinology, Diabetes and Metabolism ,Nutrition and Dietetics ,Cardiology and Cardiovascular Medicine ,endothelial dysfunction, berberine, lovastatin, oxLDL receptor-1, reactive oxygen species, tumor necrosis factor α, oxLDL ,Anti-Inflammatory Agents ,030204 cardiovascular system & hematology ,Pharmacology ,medicine.disease_cause ,Antioxidants ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Extracellular Signal-Regulated MAP Kinases ,Cells, Cultured ,Membrane Glycoproteins ,NF-kappa B ,Scavenger Receptors, Class E ,Lipoproteins, LDL ,Diabetes and Metabolism ,medicine.anatomical_structure ,Biochemistry ,NADPH Oxidase 2 ,lipids (amino acids, peptides, and proteins) ,medicine.drug ,Signal Transduction ,Endothelium ,Nitric Oxide Synthase Type III ,Cell Survival ,Socio-culturale ,03 medical and health sciences ,medicine ,Human Umbilical Vein Endothelial Cells ,Humans ,Protein kinase B ,Tumor Necrosis Factor-alpha ,NADPH Oxidases ,medicine.disease ,Angiotensin II ,Oxidative Stress ,030104 developmental biology ,chemistry ,Cytoprotection ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Oxidative stress - Abstract
Background and aims Oxidized LDL (oxLDL) or pro-inflammatory stimuli lead to increased oxidative stress linked to endothelial dysfunction and atherosclerosis. The oxLDL receptor-1 (LOX1) is elevated within atheromas and cholesterol-lowering statins inhibit LOX1 expression. Berberine (BBR), an alkaloid extracted from plants of gender Berberis, has lipid-lowering and anti-inflammatory activity. However, its role in regulating LOX1-mediated signaling is still unknown. The aim of this study was to investigate the effect of BBR on oxLDL- and TNFα-induced endothelial dysfunction in human umbilical vein endothelial cells (HUVECs) and to compare it with that of lovastatin (LOVA). Methods and results Cytotoxicity was determined by lactate dehydrogenase assay. Antioxidant capacity was measured with chemiluminescent and fluorescent method and intracellular ROS levels through a fluorescent dye. Gene and protein expression levels were assayed by qRT-PCR and western blot, respectively. HUVECs exposure to oxLDL (30 μg/ml) or TNFα (10 ng/ml) for 24 h led to a significant increase in LOX1 expression, effect abrogated by BBR (5 μM) and LOVA (5 μM). BBR but not LOVA treatment abolished the TNFα-induced cytotoxicity and restored the activation of Akt signaling. In spite of a low direct antioxidant capacity, both compounds reduced intracellular ROS levels generated by treatment of TNFα but only BBR inhibited NOX2 expression, MAPK/Erk1/2 signaling and subsequent NF-κB target genes VCAM and ICAM expression, induced by TNFα. Conclusions These findings demonstrated for the first time that BBR could prevent the oxLDL and TNFα - induced LOX1 expression and oxidative stress, key events that lead to NOX, MAPK/Erk1/2 and NF-κB activation linked to endothelial dysfunction. Chemical compounds studied in this article Berberine (PubChem CID: 2353); Lovastatin (PubChem CID: 53232).
- Published
- 2017