1. Effects of DA-9801 on the inflammation and apoptosis induced by angiotensin II in human dermal microvascular endothelial cells.
- Author
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Hong OK, Lee SS, Yoo SJ, Choi SH, Lee MK, Cha BY, Kim MK, Baek KH, Song KH, and Kwon HS
- Subjects
- Cells, Cultured, Dermis cytology, Humans, Intercellular Adhesion Molecule-1 metabolism, NADPH Oxidases metabolism, NF-kappa B metabolism, Nitric Oxide Synthase Type II metabolism, Oxidative Stress drug effects, Reactive Oxygen Species metabolism, p38 Mitogen-Activated Protein Kinases metabolism, Angiotensin II adverse effects, Apoptosis drug effects, Endothelial Cells pathology, Endothelial Cells physiology, Inflammation metabolism, Plant Preparations pharmacology
- Abstract
DA-9801, a plant-based drug used for the treatment of diabetic neuropathy, is known to improve angiotensin II (Ang II)-induced vascular endothelial cell dysfunction. However, the underlying mechanism is not fully understood. We aimed to determine whether the protective effect of DA-9801 against Ang II-induced endothelial cell dysfunction was mediated via inhibition of endothelial cell inflammation and apoptosis. Ang II-induced oxidative stress was attenuated by pretreatment of human dermal microvascular endothelial cells (HDMECs) with DA-9801. This prevented the Ang II-induced upregulation of NAD(P)H oxidase (the NOX4 and p22phox subunits) and reactive oxygen species. Further, pretreatment of HDMECs with DA-9801 ameliorated Ang II-mediated nuclear factor kappa B activity via prevention of the upregulation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase. It also decreased the Ang II-stimulated increase in inducible nitric oxide synthase (NOS) and decreased endothelial NOS protein expression. DA-9801 decreased Ang II-induced upregulation of intercellular adhesion molecule 1, vascular adhesion molecule, and E-selectin in HDMECs. Moreover, TUNEL and annexin V-FITC fluorescence staining for apoptosis and the activities of caspases 9, 7, and 3 decreased in HDMECs pretreated with DA-9801, indicating that the drug enhanced anti-apoptotic pathways. Thus, DA-9801 modulated Ang II-induced endothelial cell dysfunction via inflammatory and apoptotic pathways., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (Copyright © 2020 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)
- Published
- 2021
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