Role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the action of ginsenoside Rh2 against beta-amyloid-induced inhibition of rat brain astrocytes

Shieh, Po Chuen; Tsao, Chiung Wen; Li, Jin Shiou; Wu, Hung Tsung; Wen, Ya Ju; Kou, Dai Huang; Cheng, Juei Tang

doi:10.1016/j.neulet.2007.12.032

Cited by 43 publications

(29 citation statements)

References 42 publications

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“…It was reported that simvastatin, a cholesterol synthesis inhibitor, lowered raft cholesterol content and induced apoptosis in prostate cancer cells; however, replenishing cell membranes with cholesterol reversed these inhibitory and pro-apoptotic effects (33). In addition, previous studies have shown that ginsenoside Rh2, containing a cholesterol backbone with hydroxyl groups, induced ligand-independent Fas activation and activated caspase 8 via lipid raft disruption (34,35). Similar to Rh2, other cholesterol derivatives, such as desmosterol treatment, resulted in the disappearance of caveolae and blocked insulin receptor activation via lipid raft disruption (36).…”

Section: Discussionmentioning

confidence: 96%

Pregnenolone, a cholesterol metabolite, induces glioma cell apoptosis via activating extrinsic and intrinsic apoptotic pathways

et al. 2014

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Gliomas are one of the most common types of malignant tumors worldwide, however, an effective therapeutic strategy not yet been fully determined. The present study aimed to investigate the anti-glioma activity and underlying mechanisms of pregnenolone, which originates from cholesterol and is metabolized into important steroid hormones in the body. The results demonstrated that 100 μM pregnenolone induced a significant loss of cell viability in various malignant glioma cell lines. In the U-87 MG, LN-18 and C6 cell lines, the loss of cell viability resulted from cell apoptosis, which was evidenced by apoptotic nuclear morphology changes and caspase 3 activation. Moreover, the increased activities of caspase 8 and 9 strongly indicated that pregnenolone activated the extrinsic and intrinsic pathways of apoptosis. Additionally, glioma cell apoptosis was prevented by the general caspase inhibitor, Z-VAD-FMK. In the C6 cells, upregulation of Fas and Fas ligand triggered the activation of the extrinsic pathway, whereas knockdown of Fas significantly abrogated the cell apoptosis that was induced by pregnenolone. Furthermore, downregulation of the anti-apoptotic protein, B-cell lymphoma 2 and upregulation of pro-apoptotic proteins, such as Bax and Bak, activated the intrinsic pathway. In conclusion, pregnenolone induced glioma cell apoptosis in a caspase-dependent manner, which was mediated by activation of the extrinsic and intrinsic apoptotic pathways.

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Section: Discussionmentioning

confidence: 96%

Pregnenolone, a cholesterol metabolite, induces glioma cell apoptosis via activating extrinsic and intrinsic apoptotic pathways

et al. 2014

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“…Neuroprotective action of the ginseng extract G115 has been documented in two rodent models of Parkinson's disease [5]. We also found that ginsenoside Rh2 can against beta-amyloid-induced inhibition of rat brain astrocytes [32]. Effect of ginseng on nervous functions shall be investigated in advance.…”

Section: Other Actions Of Ginsengmentioning

confidence: 84%

Merit of Ginseng in the Improvement of Insulin Resistance

Cheng

2010

Journal of Ginseng Research

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In the present review, the merit of ginseng in the improvement of insulin resistance has been introduced. Using the results in previous studies, we found that ginseng or ginsenoside Rh2 has the ability to reduce glucose-insulin index in rats with insulin resistance. Insulin resistance was induced by feeding of fructose-rich chow in rats. Insulin resistance was characterized by regular methods. Effectiveness of ginseng powder or extract Rh2 was identified in this animal model. Also, the application of ginseng for handling of diabetic disorders in China has been discussed. According to Chinese traditional medicine, ginseng is merit in the treatment of diabetic disorders named as Shiaw-Ker in Chinese. Therefore, it is no doubt that ginseng is helpful in the control of diabetic disorders either prevention or the treatment. Otherwise, the potential effect of ginseng on nervous functions shall be investigated in the future.

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“…Hidden platform training and probe trial: Hidden platform training was performed according to Shieh et al (2008) with variable interval probes to evaluate learning and memory repeatedly. The mice were subjected to one day habituation as described above.…”

Section: Methodsmentioning

confidence: 99%

“…Among them, ginsenoside Rh2 is one of the most active and abundant components and contributes to many of the effects of ginseng. Ginsenoside Rh2 (Rh2) is known to alleviate multi-drug resistance in cancer cells and attenuate amyloid-induced cytotoxicity (Shieh et al, 2008). Multi-drug resistance proteins and amyloid beta are predominantly localized in lipid rafts, the functions of these proteins are inhibited when lipid rafts are disrupted.…”

Section: Introductionmentioning

confidence: 99%

Ginsenoside Rh2 promotes nonamyloidgenic cleavage of amyloid precursor protein via a cholesterol-dependent pathway

Qiu¹,

Li²,

Feng³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. Ginsenoside Rh2 (Rh2) is a ginseng derivative used in Chinese traditional medicine. We investigated whether Rh2 can help prevent Alzheimer's disease symptoms and examined underlying mechanisms. We injected Rh2 into tg2576 Alzheimer's disease model mice and looked for behavioral improvement and senile plaque reduction in brain slices. We measured amyloid precursor protein (APP) metabolism species changes, amyloid beta40 and 42 levels and β, γ secretase activity in primary hippocampal neurons. By living cell staining, we detected surface and endocytosed APP. We also measured cholesterol and lipid rafts in primary neurons. Rh2 treatment significantly improved learning and memory performance at 14 months of age; it also reduced brain senile plaques at this age. Based on in vitro experiments, we found that Rh2 treatment increased soluble APPα (sAPPα) levels, increased CTFα/β ratios, and reduced amyloid beta 40 3587©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 13 (2): 3586-3598 (2014) Ginsenoside Rh2 promotes nonamyloidgenic cleavage of APP and 42 concentrations. Surface APP levels dramatically increased. Based on living cell staining, we found that Rh2 inhibited APP endocytosis. Based on lipid removal and reload experiments, we found that Rh2 can modulate APP by reducing cholesterol and lipid raft levels. We concluded that Rh2 improves learning and memory function in Alzheimer's disease model mice, and that this improvement is accomplished by reducing amyloid beta secretion and APP endocytosis, which in turn is achieved by reducing cholesterol and lipid raft concentrations.

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Role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the action of ginsenoside Rh2 against beta-amyloid-induced inhibition of rat brain astrocytes

Cited by 43 publications

References 42 publications

Pregnenolone, a cholesterol metabolite, induces glioma cell apoptosis via activating extrinsic and intrinsic apoptotic pathways

Pregnenolone, a cholesterol metabolite, induces glioma cell apoptosis via activating extrinsic and intrinsic apoptotic pathways

Merit of Ginseng in the Improvement of Insulin Resistance

Ginsenoside Rh2 promotes nonamyloidgenic cleavage of amyloid precursor protein via a cholesterol-dependent pathway

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