| Description: |
Ginsenoside Re is a major ginsenoside in ginseng and belongs to 20(S)-protopanaxatriol group. It has diverse in vitro and in vivo effects, including anti-diabetic, vasorelaxant, antihyperlipidemic, anti-ischemic, angiogenic, antioxidant, and anti-inflammation actions. It also exhibits potent neuroprotective effects against neuroinflammation in a murine model of ALS. Re increases HCAEC outward current via SKCa channel activation; it also increases the proliferation of CD4+ T cells with decreases cell death, and enhances viability of CD4+T cells through the regulation of IFN-γ-dependent autophagy activity.
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| Targets: |
AMPK | TLR | p38MAPK | HO-1 | TNF-α | Potassium Channel | NO | Calcium Channel | ERK | Akt | mTOR | CD4 | Calcium Channel | c-Src | NOS |
| In vitro: |
| Eur J Pharmacol . 2016 Dec 15;793:101-108. | | Ginsenoside Re reduces Aβ production by activating PPARγ to inhibit BACE1 in N2a/APP695 cells[Pubmed: 27840193] | | Alzheimer's disease (AD) is a neurodegenerative disease characterized by β-amyloid protein (Aβ) deposition. Reducing the Aβ load may be a new perspective for AD treatment. Ginsenoside Re is an extract from Panax notoginseng, which is a well-known traditional Chinese medicine that has been used for the treatment of various diseases for years. Ginsenoside Re has been reported to decrease Aβ in Alzheimer's disease animal models, but the mechanism has not been fully elucidated. In the present study, we investigated the mechanism of ginsenoside Re. Our results showed that ginsenoside Re decreased the Aβ levels in N2a/APP695 cells. Aβ peptides are generated by β-secretase (β-site amyloid precursor protein cleaving enzyme 1 (BACE1)) and γ-secretase. We found that ginsenoside Re decreased the BACE1 mRNA and protein levels and inhibited BACE1 activity in the N2a/APP695 cells. Peroxisome proliferator-activated receptor-γ (PPARγ) is a transcription factor that regulates the activity of the BACE1 promoter, and activating PPARγ can inhibit BACE1. The results also showed that ginsenoside Re significantly increased the PPARγ protein and mRNA levels. These effects of ginsenoside Re on BACE1 could be effectively inhibited by the PPARγ antagonist GW9662. These findings indicate that ginsenoside Re inhibits BACE1 through activation of PPARγ, which ultimately reduces the generation of Aβ1-40 and Aβ1-42. Therefore, ginsenoside Re may be a promising agent for the modulation of Aβ-related pathology in AD. | | Antimicrob Agents Chemother . 2015 Sep;59(9):5654-63. | | Protective effect of ginsenosides Rg1 and Re on lipopolysaccharide-induced sepsis by competitive binding to Toll-like receptor 4[Pubmed: 26149990] | | We previously demonstrated that ginsenosides Rg1 and Re enhanced the immune response in C3H/HeB mice but not in C3H/HeJ mice carrying a mutation in the Tlr4 gene. The results of the present study showed that both Rg1 and Re inhibited mRNA expression and production of proinflammatory mediators that included tumor necrosis factor α, interleukin-1β, interleukin-6, cyclooxygenase-2, and inducible nitric oxide synthase from lipopolysaccharide (LPS)-stimulated macrophages. Rg1 was found to be distributed both extracellularly and intracellularly but Re was located only extracellularly to compete with LPS for binding to Toll-like receptor 4. Preinjection of Rg1 and Re into rats suppressed LPS-induced increases in body temperature, white blood cell counts, and levels of serum proinflammatory mediators. Preinjection of Rg1 and Re into mice prevented the LPS-induced decreases in total white blood cell counts and neutrophil counts, inhibited excessive expression of multiple proinflammatory mediators, and successfully rescued 100% of the mice from sepsis-associated death. More significantly, when administered after lethal LPS inoculation, Rg1, but not Re, still showed a potent antisepsis effect and protected 90% of the mice from death. The better protection efficacy of Rg1 could result from its intracellular distribution, suggesting that Rg1 may be an ideal antisepsis agent. |
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| In vivo: |
| Int J Mol Med. 2012 Jan;29(1):73-80. | | Ginsenoside Re lowers blood glucose and lipid levels via activation of AMP-activated protein kinase in HepG2 cells and high-fat diet fed mice.[Pubmed: 21971952 ] | Ginsenoside Re is a protopanaxatriol-type saponin isolated from Panax ginseng berry. Although anti-diabetic and anti-hyperlipidemic effects of Re have been reported by several groups, its mechanism of action is largely unknown until now.
Here, we examine anti-diabetic and anti-hyperlipidemic activities of Re and action mechanism(s) in human HepG2 hepatocytes and high-fat diet fed C57BL/6J mice.
METHODS AND RESULTS:
Re suppresses the hepatic glucose production via induction of orphan nuclear receptor small heterodimer partner (SHP), and inhibits lipogenesis via suppression of sterol regulatory element binding protein-1c (SREBP-1c) and its target gene [fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD1)] transcription. These effects were mediated through activation of AMP-activated protein kinase (AMPK), and abolished when HepG2 cells were treated with an AMPK inhibitor, Compound C. C57BL/6J mice were randomly divided into five groups: regular diet fed group (RD), high-fat diet fed group (HFD) and the HFD plus Re (5, 10, 20 mg/kg) groups. Re treatment groups were fed a high-fat diet for 6 weeks, and then orally administered Re once a day for 3 weeks. The in vitro results are likely to hold true in an in vivo experiment, as Re markedly lowered blood glucose and triglyceride levels and protected against hepatic steatosis in high-fat diet fed C57BL/6J mice.
CONCLUSIONS:
In conclusion, the current study suggest that ginsenoside Re improves hyperglycemia and hyperlipidemia through activation of AMPK, and confers beneficial effects on type 2 diabetic patients with insulin resistance and dyslipidemia. | | Cardiovasc Ther., 2012, 30(4):e183–8. | | Ginsenoside Re: pharmacological effects on cardiovascular system.[Pubmed: 21884006] | | Ginsenosides are the bioactive constituents of ginseng, a key herb in traditional Chinese medicine. As a single component of ginseng, ginsenoside Re (G-Re) belongs to the panaxatriol group. Many reports demonstrated that G-Re possesses the multifaceted beneficial pharmacological effects on cardiovascular system. G-Re has negative effect on cardiac contractility and autorhythmicity. It causes alternations in cardiac electrophysiological properties, which may account for its antiarrhythmic effect. In addition, G-Re also exerts antiischemic effect and induces angiogenic regeneration. In this review, we first outline the chemistry and the pharmacological effects of G-Re on the cardiovascular system. |
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