Ginsenoside Rg1 Downregulates miR-9-5p Expression to Modulate SIRT1-Mediated Mitochondrial Dysfunction and Ameliorate Alzheimer's Disease.

This study aimed to investigate the mechanism of ginsenoside Rg1 in Alzheimer's disease (AD) via miR-9-5p/SIRT1-mediated mitochondrial function. The cognitive function of AD mice was assessed by Morris water maze experiment. The histopathological changes in the CA1 region were observed by H&E staining. TUNEL staining combined with the neuronal marker NeuN was used to detect neuronal apoptosis in hippocampal tissues. Aβ induced HT-22 cells were used as AD in vitro models. MiR-9-5p expression was detected by qRT-PCR, and SIRT1 protein and autophagy-related proteins (LC3B II/I, Beclin-1) levels were measured by western blot. The binding of miR-9-5p with SIRT1 was predicted and validated. Ginsenoside Rg1 treatment in AD mice reduced miR-9-5p expression, increased SIRT1 level, attenuated mitochondrial dysfunction, and effectively improved AD symptoms in mice, while such effect can be either reversed by miR-9-5p agomir or SIRT1 inhibitor (EX527). In vitro, Aβ-induced HT-22 cell activity was reduced, cell death was significantly increased, and mitochondrial dysfunction was progressed, but treatment of HT-22 cells with Aβ and ginsenoside Rg1 attenuated mitochondrial dysfunction and improved Aβ-induced HT-22 cell damage. Ginsenoside Rg1 ameliorated Aβ-induced HT-22 cell damage by down-regulating miR-9-5p to regulate SIRT1-mediated mitochondrial dysfunction. miR-9-5p negatively regulates SIRT1. Inhibition of mitochondrial autophagy partially reversed the ameliorative effect of ginsenoside Rg1 on mitochondrial dysfunction and cellular damage in HT-22 cells. Ginsenoside Rg1 down-regulates miR-9-5p expression to modulate SIRT1-mediated mitochondrial dysfunction, hereby attenuating Aβ induced cell injury in HT-22 cells and alleviating AD in mice.