Ginsenoside Rg1 reduces β‑amyloid levels by inhibiting CDΚ5‑induced PPARγ phosphorylation in a neuron model of Alzheimer's disease.

Qiankun Quan, Xi Li, Jianjun Feng, Jixing Hou, Ming Li, Bingwei Zhang

Molecular medicine reports 2020 Oct

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The accumulation of β‑amyloid peptides (Aβ) in the brain is a hallmark of Alzheimer's disease (AD). Studies have indicated that ginsenoside Rg1, a primary component of ginseng (Panax ginseng), reduces brain Aβ levels in an AD model through peroxisome proliferator‑activated receptor γ (PPARγ), thereby regulating the expression of insulin‑degrading enzyme (Ide) and β‑amyloid cleavage enzyme 1 (Bace1), which are PPARγ target genes. However, the effects of ginsenoside Rg1 on PPARγ remain unclear. Since cyclin‑dependent kinase 5 (CDK5) mediates PPARγ phosphorylation in adipose tissue, this study aimed to investigate whether ginsenoside Rg1 regulates PPARγ target genes and reduces Aβ levels by inhibiting PPARγ phosphorylation through the CDK5 pathway. In the present study, a model of AD was established by treating primary cultured rat hippocampal neurons with Aβ1‑42. The cells were pretreatment with ginsenoside Rg1 and roscovitine, a CDK5‑inhibitor, prior to the treatment with Aβ1‑42. Neuronal apoptosis was detected using TUNEL staining. PPARγ phosphorylation and protein expression levels of PPARγ, CDK5, IDE, BACE1, amyloid precursor protein (APP) and Aβ1‑42 were measured by western blotting. The mRNA expression levels of PPARγ, CDK5, IDE, BACE1 and APP were assessed using reverse transcription‑quantitative PCR. The results of the present study demonstrated that in an AD model induced by Aβ1‑42, ginsenoside Rg1 significantly decreased CDK5 expression, inhibited PPARγ phosphorylation at serine 273, elevated IDE expression, downregulated BACE1 and APP expression, decreased Aβ1‑42 levels and attenuated neuronal apoptosis. The CDK5 inhibitor, roscovitine, demonstrated similar effects. These results suggest that ginsenoside Rg1 has neuroprotective properties and has potential for use in the treatment of AD.

Citation

Qiankun Quan, Xi Li, Jianjun Feng, Jixing Hou, Ming Li, Bingwei Zhang. Ginsenoside Rg1 reduces β‑amyloid levels by inhibiting CDΚ5‑induced PPARγ phosphorylation in a neuron model of Alzheimer's disease. Molecular medicine reports. 2020 Oct;22(4):3277-3288