Multifaceted neuroprotection of ginsenosides: Mechanisms, nano-delivery advances, and therapeutic potential in central nervous system disorders.
Li Linhan, Yu Yan, Fan Jinlin, Zhang Naibo, Yang Jiashuo, Li Honghe, Zheng Jian
Abstract
BACKGROUND: Central nervous system (CNS) diseases remain therapeutic challenges due to complex pathology and poor drug penetration across the blood-brain barrier (BBB). Ginsenosides, the active components of Panax ginseng, possess multi-target neuroprotective properties but exhibit low bioavailability. PURPOSE: This review synthesizes current evidence on ginsenoside mechanisms and evaluates the role of nanotechnology in enhancing their delivery and efficacy for CNS disorders. STUDY DESIGN: A systematic search was conducted following PRISMA guidelines across PubMed, Web of Science, CNKI, and Google Scholar (2015-present). Included studies investigated ginsenosides in neurological disease models and nano-formulation strategies. RESULTS: Ginsenosides modulate neuroinflammation, oxidative stress, apoptosis, and calcium homeostasis through pathways involving NF-κB, Nrf2, and Bcl-2/Bax. Nano-delivery systems-such as liposomes, polymeric nanoparticles, and biomimetic vesicles-significantly improve ginsenoside stability, BBB traversal, and brain-targeted accumulation. Functionalization with ligands (e.g., Angiopep-2) or cell membranes further enhances specificity and therapeutic outcomes in ischemic stroke, glioma, Alzheimer's disease, and spinal cord injury models. CONCLUSION: Nanotechnology-based delivery systems potently augment the neuroprotective potential of ginsenosides, offering a promising strategy for multi-target CNS therapy. Future efforts should focus on translational safety, scalable production, and clinical validation.
Key Findings
- Ginsenosides exert neuroprotective effects by modulating neuroinflammation, oxidative stress, apoptosis, and calcium homeostasis through pathways including NF-κB, Nrf2, and Bcl-2/Bax.
- Nano-delivery systems such as liposomes, polymeric nanoparticles, and biomimetic vesicles significantly enhance ginsenoside stability, blood-brain barrier penetration, and brain-targeted accumulation.
- Functionalization of nano-delivery systems with ligands or cell membranes improves targeting specificity and therapeutic outcomes in models of ischemic stroke, glioma, Alzheimer's disease, and spinal cord injury.
Clinical Significance
Nanotechnology-enhanced delivery of ginsenosides offers a promising multi-target therapeutic approach for treating central nervous system disorders, potentially overcoming current limitations in drug bioavailability and brain penetration.
Citation
Li Linhan, Yu Yan, Fan Jinlinet al.. Multifaceted neuroprotection of ginsenosides: Mechanisms, nano-delivery advances, and therapeutic potential in central nervous system disorders. Journal of ginseng research. 2026-Nov.