The mechanism of miR-665 targeting GNB3 in aluminum-induced neuronal apoptosis.

BACKGROUND: Aluminum exerts neurotoxic effects through various mechanisms, mainly manifested as impaired learning and memory function. METHODS: Forty SD rats were divided into 0, 10, 20, and 40 mM maltol aluminum [Al(mal)3] groups. Cell experiments are divided into 0, 100, 200, and 400 µM Al(mal)3 dose group and control, Al(mal)3, Al(mal)3+inhibitor NC, Al(mal)3+miR-665 inhibitor intervention group. Water maze was used to detect the learning and memory function of rats, HE staining was used to observe the morphology and number of neurons in the CA1 area of the rat hippocampus, Flow cytometry was used to detect the apoptosis of PC12 cells, PCR and Western blotting were used to detect the expression of Caspase3, miR-665 and GNB3/PI3K/AKT proteins. The target binding relationship between miR-665 and GNB3 was verified by double luciferase reporter gene experiment. RESULTS: In vivo experimental results showed that with the increase of Al(mal)3 concentration, the escape latency of rats was prolonged, the target quadrant dwell time was shortened, and the number of crossing platform was reduced. Moreover, the arrangement of neurons was loose and the number decreased; the expression of Caspase3 and miR-665 increased, while the expression of GNB3/PI3K/AKT proteins decreased. In vitro experiments, with the increase of Al(mal)3 concentration, apoptosis rate of PC12 cells increased, the expression of Caspase3, miR-665 and GNB3/PI3K/AKT proteins were consistent with rat results. After inhibiting miR-665 in the intervention group experiment, apoptosis rate of PC12 cells in the aluminum exposure group decreased, the expression of Caspase3 and miR-665 decreased, and the expression of GNB3/PI3K/AKT proteins increased. CONCLUSION: MiR-665 plays an important role in aluminum induced neuronal apoptosis by targeting GNB3 and regulating the PI3K/AKT pathway.

Liraglutide improved the cognitive function of diabetic mice via the receptor of advanced glycation end products down-regulation.

Background and aims Advanced glycation end products (AGEs) and receptor of advanced glycation end products (RAGE), are associated with cognition decline. We aim to investigate the effect of liraglutide on cognitive function in diabetic mice. Results Diabetic mice showed decreased cognitive function. Moreover, lower glucagon like peptide-1 (GLP-1) levels in plasma were detected in db/db mice. Additionally, up-regulated RAGE and down-regulated glucagon like peptide-1 (GLP-1R) levels were observed in db/db mice. However, decreased GLP-1R and increased RAGE were reversed by liraglutide. We also found decreased cellular activity in cells with AGEs. Moreover, AGEs up-regulated RAGE in PC12 and HT22 cells. However, liraglutide improved the cell activity damaged by AGEs. Although we did not discover the direct-interaction between RAGE and GLP-1R, elevated RAGE levels induced by AGEs were restored by liraglutide. Conclusion We demonstrated that the cognitive function of diabetic mice was improved by liraglutide via the down-regulation of RAGE. Methods db/db mice and db/m mice were used in this study. Liraglutide was used to remedy diabetic mice. Neurons and RAGE in hippocampus were shown by immunofluorescence. And then, PC12 cells or HT22 cells with AGEs were treated with liraglutide. GLP-1R and RAGE were measured by western blotting.

Ginsenoside Rb1 Alleviated High-Fat-Diet-Induced Hepatocytic Apoptosis via Peroxisome Proliferator-Activated Receptor γ.

OBJECTIVE: High-fat-diet- (HFD-) induced hepatic cell apoptosis is common in mice with nonalcoholic fatty liver disease (NAFLD). We aim to investigate the effect of Ginsenoside Rb1 (GRb1) on hepatocyte apoptosis. METHODS: C57BL/6J mice with HFD were used to induce a liver-injured model with cell apoptosis. In addition, GRb1 was used to treat HFD-induced apoptosis in a liver with or without inhibitor of peroxisome proliferator-activated receptor γ (PPAR-γ). RESULTS: Compared with C57BL/6J mice with common chow, there are downregulated PPAR-γ but upregulated cell apoptosis in the liver of mice with HFD. Furthermore, GRb1 elevated the hepatic PPAR-γ level and suppressed hepatocytic apoptosis. However, GW9662 abolished the effects of GRb1 on apoptosis in the liver. CONCLUSIONS: GRb1 alleviated HFD-induced apoptosis of hepatocytes of mice via PPAR-γ.

Ginsenoside Rb1 increases insulin sensitivity through suppressing 11ß-hydroxysteroid dehydrogenase type I.

Ginsenoside Rb1 (GRb1) is a major component of ginseng, which has been shown to ameliorate hyperglycemia in rodents and in humans with undetermined mechanisms. Here, we analyzed the molecular mechanisms by which GRb1 reduces the insulin resistance in high-fat diet (HFD)-induced mouse model for type 2 diabetes (T2D). HFD was applied for 4 weeks to induce T2D in mice, after which GRb1 was administrated and the effects on the fasting blood glucose, glucose tolerance and insulin sensitivity were analyzed. We found that HFD increased fasting blood glucose, glucose tolerance and reduced insulin sensitivity, which were all ameliorated by GRb1. GRb1 seemed to reduce the levels of 11ß-Hydroxysteroid dehydrogenase type I (11ß-HSD1) in liver and adipose tissue, to exert its anti-diabetes effects. Overexpression of 11ß-HSD1 completely abolished the effects of GRb1 on HFD-induced increases in fasting blood glucose and glucose tolerance, and decreases in insulin sensitivity. Together, our data suggest that GRb1 may increase insulin sensitivity through suppressing 11ß-HSD1 in treatment of T2D.