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Ginsenoside Rb1 reduces H2O2‑induced HUVEC dysfunction by stimulating the sirtuin‑1/AMP‑activated protein kinase pathway
- Source :
- Molecular Medicine Reports
- Publication Year :
- 2019
-
Abstract
- Endothelial dysfunction and senescence are closely associated with cardiovascular diseases including atherosclerosis and hypertension. Ginsenoside Rb1 (Rb1), the major active constituent of ginseng, has been investigated intensively because of its anti‑obesity and anti‑inflammatory effects. In a previous study, hydrogen peroxide (H2O2) was applied to induce human umbilical vein endothelial cell (HUVEC) aging. It was demonstrated that Sirtuin‑1 (SIRT1) was activated by Rb1 to protect HUVECs from H2O2‑induced senescence. However, the mechanisms are not fully understood. The present study examined the role of AMP‑activated protein kinase (AMPK), an energy sensor of cellular metabolism, in the signaling pathway of SIRT1 during H2O2‑stimulated HUVEC aging. It was identified that Rb1 restored the H2O2‑induced reduction of SIRT1 expression, which was consistent with our previous study, together with the activation of AMPK phosphorylation. Using compound C, an AMPK inhibitor, the role of AMPK in the protective effect of Rb1 against H2O2‑induced HUVEC senescence was examined. It was identified that the induction of phosphorylated AMPK by Rb1 markedly increased endothelial nitric oxide synthase expression and nitric oxide production, and suppressed PAI‑1 expression, which were abrogated in HUVECs pretreated with compound C. Further experiments demonstrated that nicotinamide, a SIRT1 inhibitor, downregulated the phosphorylation of AMPK and reduced the protective effects of Rb1 against H2O2‑induced endothelial aging. Taken together, these results provide new insights into the possible molecular mechanisms by which Rb1 protects against H2O2‑induced HUVEC senescence via the SIRT1/AMPK pathway.
- Subjects :
- 0301 basic medicine
Senescence
Cancer Research
Ginsenosides
Sirtuin-1
Enzyme Activators
AMP-Activated Protein Kinases
Biochemistry
Nitric oxide
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
AMP-activated protein kinase
Sirtuin 1
ginsenoside Rb1
Genetics
Humans
Protein kinase A
Molecular Biology
Cellular Senescence
human umbilical vein endothelial cells
biology
AMPK
Endothelial Cells
Hydrogen Peroxide
Articles
eye diseases
Cell biology
030104 developmental biology
Oncology
chemistry
030220 oncology & carcinogenesis
biology.protein
Molecular Medicine
Human umbilical vein endothelial cell
Signal transduction
Signal Transduction
Subjects
Details
- ISSN :
- 17913004
- Volume :
- 22
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Molecular medicine reports
- Accession number :
- edsair.doi.dedup.....c1a122e7383aa8264e0d0c7a3ba64f69