Oriquat_2026_Mol.Neurobiol_63_

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and neuronal death. Approved therapies, including acetylcholinesterase inhibitors and NMDA receptor antagonists, provide only symptomatic relief without halting progression. AD involves multifaceted pathologies: amyloid-beta (Abeta) accumulation, tau hyperphosphorylation, oxidative stress, neuroinflammation, mitochondrial dysfunction, and apoptosis. Multi-target natural compounds like ginsenosides from Panax ginseng show promise in preclinical models by modulating these pathways. Key ginsenosides (Rg1, Rb1, Rc, Rd, Re, Rg3) inhibit Abeta production (via BACE1 suppression and alpha-secretase enhancement), promote Abeta clearance (via IDE/NEP upregulation), reduce tau phosphorylation (via GSK-3beta/CDK5 modulation), and exert antioxidant, anti-inflammatory, and anti-apoptotic effects. Limited clinical evidence from small open-label trials of Korean Red Ginseng suggests cognitive improvements (e.g., in ADAS-cog and MMSE scores), with good tolerability. However, poor oral bioavailability and limited blood-brain barrier (BBB) penetration remain challenges, addressable via intranasal or nanoparticle delivery. While preclinical data are robust, clinical translation is limited by study heterogeneity and small samples. Ginsenosides warrant further investigation as adjunctive multi-target agents for AD.