Ginsenoside Re increases human coronary artery endothelial SK<inf>Ca</inf> current and nitric oxide release via glucocorticoid receptor-PI3K-Akt/PKB pathway
2
Issued Date
2025-01-01
Resource Type
ISSN
12268453
Scopus ID
2-s2.0-105004639257
Journal Title
Journal of Ginseng Research
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SCOPUS
Bibliographic Citation
Journal of Ginseng Research (2025)
Suggested Citation
Rodthongdee K., Watanapa W.B., Ruamyod K., Semprasert N., Nambundit P., Kooptiwut S., Boontaveekul L. Ginsenoside Re increases human coronary artery endothelial SK<inf>Ca</inf> current and nitric oxide release via glucocorticoid receptor-PI3K-Akt/PKB pathway. Journal of Ginseng Research (2025). doi:10.1016/j.jgr.2025.04.008 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/110181
Title
Ginsenoside Re increases human coronary artery endothelial SK<inf>Ca</inf> current and nitric oxide release via glucocorticoid receptor-PI3K-Akt/PKB pathway
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Abstract
Background: Ginsenoside Re (Re) has been shown to activate small-conductance calcium-activated potassium (SKCa) current in human coronary artery endothelial cells (HCAECs). We aimed to investigate whether Re increased SKCa current via glucocorticoid receptor (GR), its non-genomic pathway phosphoinositide 3-kinase-protein kinase B (PI3K-Akt/PKB), and endothelial nitric oxide synthase (eNOS), and whether SKCa mediated Re-induced increase in nitric oxide (NO), prostacyclin (PGI2), epoxyeicosatrienoic acid (EET), and/or hydrogen peroxide (H2O2). Methods: Whole-cell patch clamp technique was employed to study Re-activated HCAEC currents, using specific inhibitors of the proposed mediating pathway. NO and H2O2 were assayed with colorimetric methods; PGI2 and EET were investigated using ELISA. eNOS phosphorylation was assessed using Western blot analysis. Results: Re (1 μM) significantly increased HCAEC whole-cell current at +80 mV to 173.73 ± 43.90 % (mean ± SD). Apamin (SKCa blocker) could virtually eliminate Re-induced current and apamin-insensitive current could not be increased by Re, while blockers of other endothelial potassium channels did not produce the same effects. Moreover, antagonists of GR, PI3K, Akt/PKB, and eNOS effectively prevented Re's action. Re-induced eNOS phosphorylation and NO production could be prevented by blockers of SKCa, GR, or Akt/PKB, but Re-induced PGI2 production could not be prevented by apamin, while EET and H2O2 were not increased by Re. Conclusion: Re enhances SKCa current and NO production via GR-PI3K-Akt/PKB and eNOS activation; in turn, SKCa current is essential for Re-increased NO. However, Re-induced PGI2 release is independent of SKCa current. These findings could facilitate further research about ginseng effects on coronary artery and possible use in cardiovascular diseases.