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Ginsenoside Rg1 Downregulates miR-9-5p Expression to Modulate SIRT1-Mediated Mitochondrial Dysfunction and Ameliorate
Yunliang Wang1, Xiangyun Sun2, Biao He1
1College of Physical Education, AnHui Normal University, Wuhu, 241003, P.R. China.
Abstract:
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. Aβ1-42 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, Aβ1-42-induced HT-22 cell activity was reduced, cell death was significantly increased, and mitochondrial dysfunction was progressed, but treatment of HT-22 cells with Aβ1-42 and ginsenoside Rg1 attenuated mitochondrial dysfunction and improved Aβ1-42-induced HT-22 cell damage. Ginsenoside Rg1 ameliorated Aβ1-42-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 Aβ1-42 induced cell injury in HT-22 cells and alleviating AD in mice.
Insights
Ginsenoside Rg1 improves Alzheimer's disease (AD) by regulating miR-9-5p and SIRT1 to protect mitochondrial function. This natural compound alleviates cognitive decline and neuronal damage in AD models.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and neuronal loss.
- Mitochondrial dysfunction and altered autophagy are implicated in AD pathogenesis.
- Ginsenoside Rg1, a natural compound, shows potential therapeutic effects, but its precise mechanism in AD remains unclear.
Purpose of the Study:
- To investigate the therapeutic mechanism of ginsenoside Rg1 in Alzheimer's disease (AD).
- To elucidate the role of the miR-9-5p/SIRT1 signaling pathway in ginsenoside Rg1-mediated mitochondrial protection.
- To evaluate the impact of ginsenoside Rg1 on neuronal apoptosis, cognitive function, and mitochondrial homeostasis in AD models.
Main Methods:
- In vivo studies utilized Alzheimer's disease (AD) mouse models assessed via Morris water maze and histopathological analyses (H&E, TUNEL staining).
- In vitro AD models were established using Aβ1-42-induced HT-22 cells, with analyses including qRT-PCR for miR-9-5p and Western blot for SIRT1 and autophagy markers (LC3B, Beclin-1).
- Molecular interactions between miR-9-5p and SIRT1 were predicted and validated; specific inhibitors and agomirs were used to confirm pathway involvement.
Main Results:
- Ginsenoside Rg1 treatment significantly improved cognitive function and reduced neuronal apoptosis in AD mice.
- In vitro, ginsenoside Rg1 attenuated Aβ1-42-induced HT-22 cell damage and mitochondrial dysfunction by down-regulating miR-9-5p and up-regulating SIRT1.
- The protective effects of ginsenoside Rg1 were reversed by miR-9-5p agomir or SIRT1 inhibition, confirming the miR-9-5p/SIRT1 pathway's critical role.
Conclusions:
- Ginsenoside Rg1 exerts neuroprotective effects in Alzheimer's disease by modulating the miR-9-5p/SIRT1 axis.
- This mechanism involves the restoration of mitochondrial function and regulation of autophagy, thereby reducing Aβ1-42-induced cellular damage.
- Ginsenoside Rg1 represents a promising therapeutic agent for Alzheimer's disease, targeting key molecular pathways involved in neurodegeneration.
