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Ginkgolide B ameliorates oxidized low-density lipoprotein-induced endothelial dysfunction via modulating Lectin-like ox-LDL-receptor-1 and NADPH oxidase 4 expression and inflammatory cascades.
- Source :
-
Phytotherapy research : PTR [Phytother Res] 2018 Dec; Vol. 32 (12), pp. 2417-2427. Date of Electronic Publication: 2018 Aug 22. - Publication Year :
- 2018
-
Abstract
- The current study was undertaken to delineate the protective effect of Ginkgolide B, a phyto-constituent from Ginkgo biloba, on oxidized (ox)-LDL-induced endothelial dysfunction via targeting Lectin-like ox-LDL-receptor-1 (LOX-1), NADPH oxidase 4 (NOX-4), and other inflammatory proteins. Our results have shown that Ginkgolide B downregulated the expression of LOX-1 in ox-LDL-treated human umbilical vein endothelial cells (HUVECs) and RAW246.7 murine macrophages which ultimately resulted in decreased cholesterol deposits in HUVECs and RAW264.7. Moreover, Ginkgolide B suppressed the enhanced NOX4 expression, which was associated with attenuation of ROS generation in ox-LDL-stimulated HUVECs and RAW264.7 cells. Ginkgolide B also ameliorated the endothelial dysfunction by inhibiting the augmented expression of monocyte chemotactic protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in ox-LDL-activated HUVECs. Furthermore, the enhanced expression of many inflammatory cytokines in ox-LDL-induced RAW264.7 macrophages, both at transcription and protein level, was significantly down-regulated after Ginkgolide B treatment. Ginkgolide B also illustrated atheroprotective property via suppressing the augmented expression of matrix metalloproteinase-1 and cyclooxygenase-2 in ox-LDL-stimulated RAW264.7 macrophages. In summary, our study has established that Ginkgolide B ameliorates endothelial dysfunction via targeting LOX-1, NOX-4, MCP-1, ICAM-1, and VCAM-1 along with the markers associated with inflammatory cascades and thus could be promoted as a valuable therapeutic agent in prevention and management of atherosclerosis.<br /> (© 2018 John Wiley & Sons, Ltd.)
- Subjects :
- Animals
Atherosclerosis chemically induced
Atherosclerosis drug therapy
Atherosclerosis prevention & control
Cells, Cultured
Down-Regulation drug effects
Ginkgo biloba
Human Umbilical Vein Endothelial Cells drug effects
Human Umbilical Vein Endothelial Cells metabolism
Humans
Inflammation metabolism
Inflammation prevention & control
Intercellular Adhesion Molecule-1 metabolism
Macrophages drug effects
Macrophages metabolism
Mice
NADPH Oxidase 4 metabolism
Plant Extracts pharmacology
Plant Extracts therapeutic use
RAW 264.7 Cells
Scavenger Receptors, Class E metabolism
Signal Transduction drug effects
Vascular Diseases prevention & control
Ginkgolides pharmacology
Ginkgolides therapeutic use
Inflammation chemically induced
Inflammation drug therapy
Lactones pharmacology
Lactones therapeutic use
Lipoproteins, LDL
Vascular Diseases chemically induced
Vascular Diseases drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1099-1573
- Volume :
- 32
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Phytotherapy research : PTR
- Publication Type :
- Academic Journal
- Accession number :
- 30136446
- Full Text :
- https://doi.org/10.1002/ptr.6177