Ginsenoside Rg1 reduces β‑amyloid levels by inhibiting CD5K‑induced PPARγ phosphorylation in a neuron model of Alzheimer's disease

The accumulation of b‑amyloid peptides (Ab) in the brain is a hallmark of Alzheimer's disease (AD). Studies have indicated that ginsenoside Rg1, a primary component of ginseng (Panaxnginseng), reduces brain Ab levels in an AD model through peroxisome proliferator‑activated receptor g (PPARg), thereby regulating the expression of insulin‑degrading enzyme (Ide) and b‑amyloid cleavage enzyme 1 (Bace1), which are PPARg target genes. However, the effects of ginsenoside Rg1 on PPARg remain unclear. Since cyclin‑dependent kinase 5 (CDK5) mediates PPARg phosphorylation in adipose tissue, this study aimed to investigate whether ginsenoside Rg1 regulates PPARg target genes and reduces Ab levels by inhibiting PPARg phosphorylation through the CDK5 pathway. In the present study, a model of AD was established by treating primary cultured rat hippocampal neurons with Ab1‑42. The cells were pretreatment with ginsenoside Rg1 and roscovitine, a CDK5‑inhibitor, prior to the treatment with Ab1‑42. Neuronal apoptosis was detected using TUNEL staining. PPARg phosphorylation and protein expression levels of PPARg, CDK5, IDE, BACE1, amyloid precursor protein (APP) and Ab1‑42 were measured by western blotting. The mRNA expression levels of PPARg, 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 Ab1‑42, ginsenoside Rg1 significantly decreased CDK5 expression, inhibited PPARg phosphorylation at serine 273, elevated IDE expression, downregulated BACE1 and APP expression, decreased Ab1‑42 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.