Ginsenoside Rg3 increases nitric oxide production via increases in phosphorylation and expression of endothelial nitric oxide synthase: Essential roles of estrogen receptor-dependent PI3-kinase and AMP-activated protein kinase

Journal Article · Sun Aug 01 00:00:00 EDT 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2010.05.008· OSTI ID:21460194

Hien, Tran Thi ^[1]; Kim, Nak Doo ^[2]; Pokharel, Yuba Raj ^[1]; Oh, Seok Jeong; Lee, Moo Yeol ^[3]

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1. BK21 Project Team, College of Pharmacy, Chosun University, 375 Seosuk-dong, Dong-gu, Gwangju 501-759 (Korea, Republic of)
2. Seoul National University, Seoul 151-745 (Korea, Republic of)
3. College of Pharmacy, Chonnam National University, Gwangju 500-757 (Korea, Republic of)

We previously showed that ginsenosides increase nitric oxide (NO) production in vascular endothelium and that ginsenoside Rg3 (Rg3) is the most active one among ginseng saponins. However, the mechanism for Rg3-mediated nitric oxide production is still uncertain. In this study, we determined whether Rg3 affects phosphorylation and expression of endothelial nitric oxide synthase (eNOS) in ECV 304 human endothelial cells. Rg3 increased both the phosphorylation and the expression of eNOS in a concentration-dependent manner and a maximal effect was found at 10 {mu}g/ml of Rg3. The enzyme activities of phosphatidylinositol 3-kinase (PI3-kinase), c-Jun N-terminal kinase (JNK), and p38 kinase were enhanced as were estrogen receptor (ER)- and glucocorticoid receptor (GR)-dependent reporter gene transcriptions in Rg3-treated endothelial cells. Rg3-induced eNOS phosphorylation required the ER-mediated PI3-kinase/Akt pathway. Moreover, Rg3 activates AMP-activated protein kinase (AMPK) through up-regulation of CaM kinase II and Rg3-stimulated eNOS phosphorylation was reversed by AMPK inhibition. The present results provide a mechanism for Rg3-stimulated endothelial NO production.

• OSTI ID: 21460194
• Journal Information: Toxicology and Applied Pharmacology, Vol. 246, Issue 3; Other Information: DOI: 10.1016/j.taap.2010.05.008; PII: S0041-008X(10)00174-2; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ENDOTHELIUM
ESTROGENS
GLUCOCORTICOIDS
NITRIC OXIDE
PHOSPHORYLATION
PHOSPHOTRANSFERASES
RECEPTORS
ADRENAL HORMONES
ANIMAL TISSUES
BODY
CHALCOGENIDES
CHEMICAL REACTIONS
CORTICOSTEROIDS
ENZYMES
HORMONES
HYDROXY COMPOUNDS
KETONES
MEMBRANE PROTEINS
NITROGEN COMPOUNDS
NITROGEN OXIDES
ORGANIC COMPOUNDS
OXIDES
OXYGEN COMPOUNDS
PHOSPHORUS-GROUP TRANSFERASES
PREGNANES
PROTEINS
STEROID HORMONES
STEROIDS
TRANSFERASES