Unraveling the therapeutic potential of ginsenoside compound Mc1 in Alzheimer's disease: Exploring the role of AMPK/SIRT1/NF-κB signaling pathway and mitochondrial function.

BACKGROUND

Alzheimer's disease (AD) is a disabling neurodegenerating disorder characterized by chronic neuroinflammation, cognitive impairment and memory loss. Current treatment options for AD offer limited benefits, underscoring the urgent need for alternative therapeutics. Despite the promising effects of ginsenosides in neurodegenerative diseases, the therapeutic potential of ginsenoside compound Mc1 (GCMc1) in AD remains to be thoroughly investigated.

OBJECTIVES

This study aimed to investigate the therapeutic potential of GCMc1 in rats with AD and to elucidate the molecular mechanisms responsible for its effects.

MATERIAL AND

METHODS

Alzheimer's disease was induced in Sprague Dawley rats through a single intra-cerebro-ventricular injection of amyloid-beta (Aβ)1-42 peptide. The animals were divided into 5 groups: a control group and 4 AD subgroups, with or without receiving 10 mg/kg of GCMc1 and/or 100 μg/kg of compound C intraperitoneally (ip.). Behavioral tests, mitochondrial function, inflammatory cytokines, and proteins expression were evaluated using the Morris water maze (MWM) test, fluorometry, enzyme-linked immunosorbent assay (ELISA), and immunoblotting techniques, respectively.

RESULTS

Treatment with GCMc1 improved cognitive function, reduced hippocampal Aβ accumulation, and suppressed interleukin (IL)-1β, IL-10 and tumor necrosis factor alpha (TNF-α) levels. Ginsenoside compound Mc1 reduced mitochondrial reactive oxygen species (ROS) levels and membrane depolarization, increased adenosine triphosphate (ATP) levels, upregulated the expression of AMPK, PGC-1α and SIRT1 proteins, and downregulated the nuclear factor-kappa-B (NF-κB) expression. Importantly, co-administration of compound C, an AMPK inhibitor, attenuated the beneficial effects of GCMc1, suggesting the involvement of AMPK pathway in mediating GCMc1's neuroprotective effects.

CONCLUSIONS

We showed that GCMc1 confers substantial neuroprotection in rats with AD by modulating the AMPK/SIRT1/NF-κB signaling pathway. These findings highlight the potential of GCMc1 as a promising therapeutic agent for AD treatment.