| Description: |
Ginsenoside Rg2 has therapeutic potential for type 2 diabetic patients, it also may represent a potential neurorestorative treatment strategy for vascular dementia or other ischemic insults, has protective effects against H2O2-induced injury and apoptosis in H9c2 cells. Ginsenoside Rg2 suppresses the hepatic glucose production via AMPK-induced phosphorylation of GSK3β and induction of SHP gene expression, regulates the 5-HT3A receptors that are expressed in Xenopus oocytes, inhibits nicotinic acetylcholine receptor-mediated Na+ influx and channel activity. |
| Targets: |
NF-kB | p38MAPK | PI3K | MEK | ERK | JNK | IkB | AMPK | GSK-3 | cAMP | Caspase | Bcl-2/Bax | p53 | IKK |
| In vitro: |
| Korean J Physiol Pharmacol. 2013 Apr;17(2):133-7. | | Ginsenoside rg2 inhibits lipopolysaccharide-induced adhesion molecule expression in human umbilical vein endothelial cell.[Pubmed: 23626475] | Vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), P- and E-selectin play a pivotal role for initiation of atherosclerosis. Ginsenoside, a class of steroid glycosides, is abundant in Panax ginseng root, which has been used for prevention of illness in Korea.
In this study, we investigated the mechanism(s) by which ginsenoside Rg2 may inhibit VCAM-1 and ICAM-1 expressions stimulated with lipopolysaccharide (LPS) in human umbilical vein endothelial cell (HUVEC).
METHODS AND RESULTS:
LPS increased VCAM-1 and ICAM-1 expression. Ginsenoside Rg2 prevented LPS-mediated increase of VCAM-1 and ICAM-1 expression. On the other hand, JSH, a nuclear factor kappa B (NF-κB) inhibitor, reduced both VCAM-1 and ICAM-1 expression stimulated with LPS. SB202190, inhibitor of p38 mitogen-activated protein kinase (p38 MAPK), and wortmannin, phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, reduced LPS-mediated VCAM-1 but not ICAM-1 expression. PD98059, inhibitor of mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) did not affect VCAM-1 and ICAM-1 expression stimulated with LPS. SP600125, inhibitor of c-Jun N-terminal kinase (JNK), reduced LPS-mediated ICAM-1 but not VCAM-1 expression. LPS reduced IkappaBα (IκBα) expression, in a time-dependent manner within 1 hr. Ginsenoside Rg2 prevented the decrease of IκBα expression stimulated with LPS. Moreover, ginsenoside Rg2 reduced LPS-mediated THP-1 monocyte adhesion to HUVEC, in a concentration-dependent manner.
CONCLUSIONS:
These data provide a novel mechanism where the ginsenoside Rg2 may provide direct vascular benefits with inhibition of leukocyte adhesion into vascular wall thereby providing protection against vascular inflammatory disease. | | Chem Biol Interact. 2012 Jan 5;195(1):35-42. | | Ginsenoside Rg2 induces orphan nuclear receptor SHP gene expression and inactivates GSK3β via AMP-activated protein kinase to inhibit hepatic glucose production in HepG2 cells.[Pubmed: 22062806] | Panax ginseng is known to have anti-diabetic activity, but the active ingredients have not been fully explored yet. Here, we test whether
Ginsenoside Rg2 has an inhibitory effect on hepatic glucose production and determine its mechanism of action.
METHODS AND RESULTS:
Ginsenoside Rg2 significantly inhibits hepatic glucose production and induces phosphorylations of liver kinase B1 (LKB1), AMP-activated protein kinase (AMPK) and glycogen synthase kinase 3β (GSK3β) in time- and concentration-dependent manners in human HepG2 hepatoma cells, and these effects were abolished in the presence of compound C, a selective AMPK inhibitor. In addition, phosphorylated form of cAMP-response element-binding protein (CREB), a key transcription factor for hepatic gluconeogenesis, was decreased in time- and concentration-dependent manners. Next, gene expression of orphan nuclear receptor small heterodimer partner (SHP) was also examined. Ginsenoside Rg2 markedly enhanced the gene expression of SHP and its direct interaction with CREB, which results in disruption of CREB·CRTC2 complex. Consequently, expressions of relevant genes such as peroxisome proliferation-activated receptor γ coactivator-1α (PGC-1α), phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) were all significantly suppressed and these effects were also reversed in the presence of compound C. In conclusion, our results propose that
CONCLUSIONS:
Ginsenoside Rg2 suppresses the hepatic glucose production via AMPK-induced phosphorylation of GSK3β and induction of SHP gene expression. Further studies are warranted to elucidate a therapeutic potential of Ginsenoside Rg2 for type 2 diabetic patients. |
|
| In vivo: |
| Progress in Modern Biomedicine, 2010,10(06):1069-75. | | Ginsenoside Rg2 attenuates learning and memory loss through an anti-apoptotic property in a rat model of multi-infarct dementia.[Reference: WebLink] | We evaluated the neurorestorative effects of Ginsenoside Rg2,one of the main bioactive components of Panax ginseng,in a rat model of multi-infarct dementia (MID).
CONCLUSIONS:
A MID rat model was established as produced by multiple cerebral infarctions induced by means of a thrombo-inducer.Y-maze learning performance was assessed after thrombo-induction.Results: Immunocytochemical techniques were employed to assess cell apoptosis as measured by protein expressions of glutamate,calpainⅡ,caspase-3 and bax.Learning and memory performance were impaired by thrombo-inductor induced MID and the expression of glutamate,calpainⅡ,caspase-3 and bax were increased in this MID rat model.After Ginsenoside Rg2 (2.5,5 or 10 mg/kg) or nimodipine (50μg/kg) treatment,learning and memory performance was increased and the expression of glutamate,calpain Ⅱ,caspase-3 and bax were decreased in this MID model.
CONCLUSIONS:
These findings suggest that Ginsenoside Rg2 improved learning and memory through mechanisms related to anti-apoptosis in MID rats.These results also indicate that Ginsenoside Rg2 may represent a potential neurorestorative treatment strategy for vascular dementia or other ischemic insults. | | 2016 Jan;40(1):9-17. | | A UPLC/MS-based metabolomics investigation of the protective effect of ginsenosides Rg1 and Rg2 in mice with Alzheimer's disease[Pubmed: 26843817] | | Abstract
Background: Alzheimer's disease (AD) is a progressive brain disease, for which there is no effective drug therapy at present. Ginsenoside Rg1 (G-Rg1) and G-Rg2 have been reported to alleviate memory deterioration. However, the mechanism of their anti-AD effect has not yet been clearly elucidated.
Methods: Ultra performance liquid chromatography tandem MS (UPLC/MS)-based metabolomics was used to identify metabolites that are differentially expressed in the brains of AD mice with or without ginsenoside treatment. The cognitive function of mice and pathological changes in the brain were also assessed using the Morris water maze (MWM) and immunohistochemistry, respectively.
Results: The impaired cognitive function and increased hippocampal Aβ deposition in AD mice were ameliorated by G-Rg1 and G-Rg2. In addition, a total of 11 potential biomarkers that are associated with the metabolism of lysophosphatidylcholines (LPCs), hypoxanthine, and sphingolipids were identified in the brains of AD mice and their levels were partly restored after treatment with G-Rg1 and G-Rg2. G-Rg1 and G-Rg2 treatment influenced the levels of hypoxanthine, dihydrosphingosine, hexadecasphinganine, LPC C 16:0, and LPC C 18:0 in AD mice. Additionally, G-Rg1 treatment also influenced the levels of phytosphingosine, LPC C 13:0, LPC C 15:0, LPC C 18:1, and LPC C 18:3 in AD mice.
Conclusion: These results indicate that the improvements in cognitive function and morphological changes produced by G-Rg1 and G-Rg2 treatment are caused by regulation of related brain metabolic pathways. This will extend our understanding of the mechanisms involved in the effects of G-Rg1 and G-Rg2 on AD.
Keywords: Alzheimer's disease; ginseng; ginsenoside Rg1; ginsenoside Rg2; metabolomics. |
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