Ginsenoside Rg1 promotes nonamyloidgenic cleavage of APP via estrogen receptor signaling to MAPK/ERK and PI3K/Akt

Shi, Chun; Zheng, Duo; Li, Fang; Wu, Fengming; Kwong, Wing Hang; Xu, Jie

doi:10.1016/j.bbagen.2011.12.005

Cited by 76 publications

(46 citation statements)

References 63 publications

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“…It has been suggested that the PI3K/Akt pathway is important for insulin signal transduction, cell cycle, cell growth, and survival regulation in DM (Matsui and Davidoff, 2007), and activation of the PI3K/Akt pathway is considered protective against the development of diabetic cardiomyopathy. Indeed, many previous studies have shown that treatment with Rg1 was associated with the activation of the PI3K/Akt pathway in human endothelial cells (Leung et al, 2006), hippocampal neuronal cells (Shi et al, 2012), and macrophages (Wang et al, 2014). However, a recent study indicated that Rg1 may protect chondrocyte from interleukin-1β-induced apoptosis via inhibiting the phosphorylation of Akt (Huang et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rg1 ameliorates oxidative stress and myocardial apoptosis in streptozotocin-induced diabetic rats

Zhen

Pang

et al. 2015

J. Zhejiang Univ. Sci. B

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Abstract:We evaluated the cardioprotective effects of ginsenoside Rg1 in a diabetic rat model induced with high-fat diet and intraperitoneal injection of streptozotocin. Ginsenoside Rg1 was injected intraperitoneally for 12 weeks. Myocardial injury indices and oxidative stress markers were determined. Changes in cardiac ultrastructure were evaluated with transmission electron microscopy. Myocardial apoptosis was assessed via terminal deoxynucleotidyl transferase (TDT)-mediated DNA nick-end labeling (TUNEL) and immunohistochemistry. Ginsenoside Rg1 was associated with a significant dose-dependent reduction in serum levels of creatinine kinase MB and cardiac troponin I, and lessened ultrastructural disorders in diabetic myocardium, relative to the untreated diabetic model rats. Also, compared with the untreated diabetic rats, significant reductions in serum and myocardial levels of malondialdehyde were noted in the ginsenoside Rg1-treated groups, and increased levels of the antioxidants (superoxide dismutase, catalase, and glutathione peroxidase) were detected. TUNEL staining indicated reduced myocardial apoptosis in ginsenoside Rg1-treated rats, which may be associated with reduced levels of caspase-3 (CASP3) and increased levels of B-cell lymphoma-extra-large (Bcl-xL) in the diabetic myocardium. Ginsenoside Rg1 treatment of diabetic rats was associated with reduced oxidative stress and attenuated myocardial apoptosis, suggesting that ginsenoside Rg1 may be of potential preventative and therapeutic value for cardiovascular injury in diabetic patients.

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Section: Discussionmentioning

confidence: 99%

Ginsenoside Rg1 ameliorates oxidative stress and myocardial apoptosis in streptozotocin-induced diabetic rats

Zhen

Pang

et al. 2015

J. Zhejiang Univ. Sci. B

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“…Additionally, the promotion of non-amyloidogenic APP processing by Tan IIA required activation of PI3K̸Akt signaling rather than direct interaction between α-secretase and Tan IIA. In our previous studies, we reported that ER-mediated PI3K/Akt signaling is involved in APP metabolism (1,11), suggesting that the effect of Tan IIA on APP metabolism may be associated with its estrogenic activity. In this study, the effect of Tan IIA on platelet APP metabolism was inhibited blocked by the ER antagonists and the PI3K inhibitor.…”

Section: Discussionmentioning

confidence: 99%

“…It was demonstrated that ER-mediated PI3K/Akt signaling is involved in APP metabolism (1,11). Tan IIA is known to be a phytoestrogen and may activate ER-mediated signaling, such as PI3K/Akt (7,10).…”

Section: Er-mediated Pi3k/akt Signaling Is Involved In the Effect Ofmentioning

confidence: 99%

“…For example, in lipopolysaccharide-treated RAW 264.7 cells, Tan IIA was shown to inhibit the expression of inducible nitric oxide synthase, the production of nitric oxide and the release of inflammatory cytokines, such as interleukin (IL)-1β, IL-6 and tumor necrosis factor-α via an ER-dependent pathway (10). In our previous studies, we demonstrated that ER-mediated PI3K/Akt signaling promotes α-secretase cleavage of APP and inhibits the production of Aβ (1,11). In this study, we aimed to Tanshinone IIA promotes non-amyloidogenic processing of amyloid precursor protein in platelets via estrogen receptor signaling to phosphatidylinositol 3-kinase/Akt assess whether Tan IIA modulates platelet APP metabolism via an ER-dependent pathway.…”

Section: Introductionmentioning

confidence: 99%

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Tanshinone IIA promotes non-amyloidogenic processing of amyloid precursor protein in platelets via estrogen receptor signaling to phosphatidylinositol 3-kinase/Akt

et al. 2014

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Abstract. Amyloid β peptide (Aβ) is a proteolytic product of amyloid precursor protein (APP). Recent findings suggested that platelet-derived Aβ is closely associated with the pathogenesis of atherosclerosis (AS). Tanshinone IIA (Tan IIA), a pharmacologically active component of the Chinese herb Salvia miltiorrhiza Bunge, has long been used to treat AS and was also identified as a phytoestrogen. However, it has not been elucidated whether Tan IIA intervenes with platelet APP processing and whether such an intervention is associated with its estrogenic activity. Using human platelets, this study demonstrated that Tan IIA promoted the non-amyloidogenic cleavage of APP via estrogenic activity. The phosphatidylinositol 3-kinase̸Akt pathway may be involved in this effect of Tan IIA on platelet APP metabolism as a downstream effector of estrogen receptor signaling. This study aimed to extend the existing data and provide new insights into the mechanism underlying the vasoprotective effect of Tan IIA.

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“…41 Ginsenoside Rg1 protected cells by antagonizing apoptosis 42 and exhibited neuroprotective effects; 43 in addition, Rg1 is an antiapoptotic molecule that is capable of blocking the caspase-dependent signaling cascade in Jurkat cells. 44 Ginsenoside Rg1 exhibited attenuated methamphetamine-induced dopaminergic degeneration in vivo through the inhibition of impaired enzymatic antioxidant systems, mitochondrial oxidative stress and apoptosis, 43 while ginsenoside Rb1 prevented apoptosis induced by amyloid. 44,45 The main constituents in hydroethanolic extract from powdered roots of H. tomentosa were caffeoylquinic derivatives and taxifolin derivatives (astilbin).…”

Section: Central Nervous System Protection Of Ginsenosides Caffeoyl mentioning

confidence: 99%

PHYTOCHEMICAL ANALYSIS OF HYDROETHANOLIC EXTRACTS FROM POWDERED ROOTS OFPanax ginsengC. A. Meyer ANDHeteropterys tomentosaA. Juss AND EVALUATION OF THEIR EFFECTS ON ASTROCYTE CELL DEATH

Bezerra¹,

Negri²,

Duarte-Almeida³

et al. 2016

Química Nova

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The medicinal plants Panax ginseng C. A. Meyer (Araliaceae) and Heteropterys tomentosa A. Juss (Malpighiaceae) are widely and separately used by the Brazilian population as phytotherapeutics for the same medicinal purposes as tonics and to improve cognition. A chemical analysis was carried out on hydroethanolic extracts of powdered roots from P. ginseng and H. tomentosa using HPLC-DAD-ESI-MS/MS (High Performance Liquid Chromatography coupled to Diode-Array Detector and Electrospray Ionization -Mass Spectrum/Mass Spectrum). The ginsenosides Rg1, Rf, mRg and mRf were the main constituents in a hydroethanolic extract from P. ginseng, while in the hydroethanolic extract from H. tomentosa, caffeoylquinic acid derivatives and astilbin isomers were the main constituents. Concentration-time-effect curves were generated in cultures of astrocytes that were incubated with hydroethanolic extracts of these species to elucidate their toxicities. The P. ginseng extract was nontoxic at all of the tested times and concentrations. The hydroethanolic extract from H. tomentosa demonstrated toxicity at a concentration of 1000 µg/mL. P. ginseng extract had no protective effect against staurosporine. Many studies have demonstrated the neuroprotective effect of ginsenosides, caffeoylquinic derivatives and flavonoids.

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Ginsenoside Rg1 promotes nonamyloidgenic cleavage of APP via estrogen receptor signaling to MAPK/ERK and PI3K/Akt

Cited by 76 publications

References 63 publications

Ginsenoside Rg1 ameliorates oxidative stress and myocardial apoptosis in streptozotocin-induced diabetic rats

Ginsenoside Rg1 ameliorates oxidative stress and myocardial apoptosis in streptozotocin-induced diabetic rats

Tanshinone IIA promotes non-amyloidogenic processing of amyloid precursor protein in platelets via estrogen receptor signaling to phosphatidylinositol 3-kinase/Akt

PHYTOCHEMICAL ANALYSIS OF HYDROETHANOLIC EXTRACTS FROM POWDERED ROOTS OFPanax ginsengC. A. Meyer ANDHeteropterys tomentosaA. Juss AND EVALUATION OF THEIR EFFECTS ON ASTROCYTE CELL DEATH

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