Ginsenosides for Multi-target Intervention in Alzheimer's Disease: Current Evidence, Challenges, and Future Directions.

2026-01
Molecular neurobiology 63(1)
- Ghaleb Oriquat
- Afaq Mahdi Ali
- Malathi H
- Israa Abdulhameed Ahmad
- Laxmidhar Maharana
- Laxmidhar Maharana
- Ashish Singh Chauhan
- Vimal Arora
- Bilakshan Purohit
- Manoj Kumar-Mishra

PubMed: 42141250
DOI: 10.1007/s12035-026-05910-z

Study Design

Type: Review

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-β (Aβ) 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 Aβ production (via BACE1 suppression and α-secretase enhancement), promote Aβ clearance (via IDE/NEP upregulation), reduce tau phosphorylation (via GSK-3β/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.

Research Insights

Red Ginseng→Improved Alzheimer Disease Assessment Scale-Cognitive Subscale Score
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.
Effect
Beneficial
Effect size
Small
Red Ginseng→Improved Cognitive Function
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.
Effect
Beneficial
Effect size
Small
Red Ginseng→Improved Mini-Mental State Examination Score
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.
Effect
Beneficial
Effect size
Small

Adverse Events Reported

Red Ginseng→Overall tolerability
with good tolerability
Finding
Reported