Ginkgo biloba extract attenuates oxLDL-induced endothelial dysfunction via an AMPK-dependent mechanism
Abstract
Atherosclerosis is a complex inflammatory arterial disease, and oxidized low-density lipoprotein (oxLDL) is directly associated with chronic vascular inflammation. Previous studies have shown that Ginkgo biloba extract (GbE) acts as a therapeutic agent for neurological and cardiovascular disorders. However, the mechanisms mediating the actions of GbE are still largely unknown. In the present study, we tested the hypothesis that GbE protects against oxLDL-induced endothelial dysfunction via an AMP-activated protein kinase (AMPK)-dependent mechanism. Human umbilical vein endothelial cells were treated with GbE, followed by oxLDL, for indicated time periods. Results from Western blot showed that GbE inhibited the membrane translocation of the NADPH oxidase subunits p47(phox) and Rac-1 and attenuated the increase in protein expression of membrane subunits gp91 and p22(phox) caused by oxLDL-induced AMPK dephosphorylation and subsequent PKC activation. AMPK-α(1)-specific small interfering RNA-transfected cells that had been exposed to GbE followed by oxLDL revealed elevated levels of PKC and p47(phox). In addition, exposure to oxLDL resulted in reduced AMPK-mediated Akt/endothelial nitric oxide (NO) synthase signaling and the induction of phosphorylation of p38 mitogen-activated protein kinase, which, in turn, activated NF-κB-mediated inflammatory responses, such as the release of interleukin-8, the expression of the adhesion molecule, and the adherence of monocytic cells to human umbilical vein endothelial cells. Furthermore, oxLDL upregulated the expression of inducible NO synthase, thereby augmenting the formation of NO and protein nitrosylation. Pretreatment with GbE, however, exerted significant cytoprotective effects in a dose-dependent manner. Results from this study may provide insight into a possible molecular mechanism by which GbE protects against oxLDL-induced endothelial dysfunction.
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AMPK suppresses protein kinase C activity and prevents protein kinase C modulation of p47phox phosphorylation.
“AMPK suppresses protein kinase C activity and prevents protein kinase C modulation of p47phox phosphorylation [152].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [152]
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- Authors
- Ou, H.-C., Hsieh, Y.-L., Yang, N.-C., Tsai, K.-L., Chen, K.-L., Tsai, C.-S., Chen, I.-J., Wu, B.-T., & Lee, S.-D.
- Affiliations
- China Medical University (TW)
- Chung Shan Medical University Hospital (TW)
- Taichung Veterans General Hospital (TW)
- Asia University (TW)
- Corresponding author
- Lee, Shin-Da
- ORCID
- Venue
- Journal of Applied Physiology
- Publisher
- American Physiological Society
- Published
- 2013-01-15
- Volume
- 114
- Issue
- 2
- Pages
- 274-285
- ISSN
- 0161-7567 (ISSN-L)
- 8750-7587
- 1522-1601
- OpenAlex
- W2108233199
- Cited by
- 34
- References
- 38
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 4 · 2018: 6 · 2017: 7 · 2015: 3 · 2014: 3 · 2013: 1
- FWCI
- 1.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Applied Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Complementary and alternative medicine › Ginkgo biloba and Cashew Applications
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- Ginkgo biloba extract, oxidized LDL, endothelial dysfunction, AMPK, atherosclerosis, NADPH oxidase, Rac1, p47phox, protein kinase C, p38 MAPK, NF-κB, vascular inflammation, inducible nitric oxide synthase, protein nitrosylation, interleukin-8, monocyte adhesion, endothelial protection
- MeSH terms
- Cells, Cultured, Endothelium, Vascular, Humans, Lipoproteins, LDL, Plant Extracts, Protein Kinase C, Umbilical Veins, Signal Transduction, NF-kappa B, Reactive Oxygen Species, NADPH Oxidases, Ginkgo biloba, Proto-Oncogene Proteins c-akt, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type III, AMP-Activated Protein Kinases
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