Document Type
Poster Presentation
Location
Oxford Conference Center
Event Website
https://oxfordicsb.org/
Start Date
21-4-2026 1:00 PM
End Date
21-4-2026 2:30 PM
Description
Red ginseng and its bioactive constituents, ginsenosides, have long been associated with neuroprotection and anti-aging effects, yet their limited ability to cross the blood-brain barrier (BBB) and poorly characterized biodistribution have hindered therapeutic translation. To address this, we developed a library of “ginsenoprobes” by conjugating major red ginseng components (Rg1, Rg3, Rb1, Rh2, Rk1, Rg5) and red ginseng extract (RGE) to a zwitterionic near-infrared (NIR) fluorophore (ZW800-1C), enabling real-time tracking of their fate in vitro and in vivo. All ginsenoprobes were purified to >95% homogeneity via preparative HPLC and rigorously characterized for optical properties, including molar extinction coefficients and dye-to-ginsenoside ratios. In vitro studies in Neuro-2a and SH-SY5Y neuronal cell lines revealed distinct, cell-type-dependent uptake patterns, with ZW800-Rb1, ZW800-Rh2, and ZW800-Rg3 exhibiting the highest internalization in SH-SY5Y cells. Confocal microscopy confirmed probe distribution to lysosomes, mitochondria, and other intracellular compartments, suggesting multifocal bioactivity. Cytotoxicity screening established a safe therapeutic window (≤10 µM), while higher concentrations (20 µM) of the more lipophilic ZW800-Rh2 and ZW800-Rk1 induced cell death. In vivo, intravenous administration of ZW800-Rg1 in CD-1 mice enabled real-time NIR fluorescence imaging, demonstrating rapid renal clearance, minimal off-target accumulation, and, critically, significant and sustained penetration across the BBB. Ex vivo brain imaging and fluorescence microscopy confirmed parenchymal distribution throughout cortical and subcortical regions up to 12 h post-injection. Pharmacokinetic analysis revealed a distribution half-life of approximately 15 min and an elimination half-life of 4.5 h, supporting a favorable safety and clearance profile. These findings establish ginsenoprobes as a powerful theranostic platform to directly visualize and quantify the brain bioavailability of red ginseng components. The demonstrated brain-targeting capability of ZW800-Rg1, combined with its favorable cellular uptake and safety profile, positions it as a lead candidate for future investigations into ginsenoside-based therapies aimed at combating neurodegeneration and promoting brain anti-aging
Recommended Citation
Choi, Hak Soo, "Ginsenoside-Based Theranostic Agents for Alzheimer's Disease: Implications for Brain Penetration, Cellular Uptake, and Anti-Aging Effects" (2026). Oxford ICSB. 11.
https://egrove.olemiss.edu/icsb/2026_ICSB/Schedule/11
Publication Date
April 2026
Accessibility Status
Screen reader accessible, Searchable text
Included in
Ginsenoside-Based Theranostic Agents for Alzheimer's Disease: Implications for Brain Penetration, Cellular Uptake, and Anti-Aging Effects
Oxford Conference Center
Red ginseng and its bioactive constituents, ginsenosides, have long been associated with neuroprotection and anti-aging effects, yet their limited ability to cross the blood-brain barrier (BBB) and poorly characterized biodistribution have hindered therapeutic translation. To address this, we developed a library of “ginsenoprobes” by conjugating major red ginseng components (Rg1, Rg3, Rb1, Rh2, Rk1, Rg5) and red ginseng extract (RGE) to a zwitterionic near-infrared (NIR) fluorophore (ZW800-1C), enabling real-time tracking of their fate in vitro and in vivo. All ginsenoprobes were purified to >95% homogeneity via preparative HPLC and rigorously characterized for optical properties, including molar extinction coefficients and dye-to-ginsenoside ratios. In vitro studies in Neuro-2a and SH-SY5Y neuronal cell lines revealed distinct, cell-type-dependent uptake patterns, with ZW800-Rb1, ZW800-Rh2, and ZW800-Rg3 exhibiting the highest internalization in SH-SY5Y cells. Confocal microscopy confirmed probe distribution to lysosomes, mitochondria, and other intracellular compartments, suggesting multifocal bioactivity. Cytotoxicity screening established a safe therapeutic window (≤10 µM), while higher concentrations (20 µM) of the more lipophilic ZW800-Rh2 and ZW800-Rk1 induced cell death. In vivo, intravenous administration of ZW800-Rg1 in CD-1 mice enabled real-time NIR fluorescence imaging, demonstrating rapid renal clearance, minimal off-target accumulation, and, critically, significant and sustained penetration across the BBB. Ex vivo brain imaging and fluorescence microscopy confirmed parenchymal distribution throughout cortical and subcortical regions up to 12 h post-injection. Pharmacokinetic analysis revealed a distribution half-life of approximately 15 min and an elimination half-life of 4.5 h, supporting a favorable safety and clearance profile. These findings establish ginsenoprobes as a powerful theranostic platform to directly visualize and quantify the brain bioavailability of red ginseng components. The demonstrated brain-targeting capability of ZW800-Rg1, combined with its favorable cellular uptake and safety profile, positions it as a lead candidate for future investigations into ginsenoside-based therapies aimed at combating neurodegeneration and promoting brain anti-aging
https://egrove.olemiss.edu/icsb/2026_ICSB/Schedule/11
Comments
Dr. Hak Soo Choi is a Professor and Director of Bioengineering and Nanomedicine at the ADA Forsyth Institute, where he leads a visionary program at the intersection of molecular imaging and targeted theranostics. Before his current role, he led a multidisciplinary team of more than 20 specialists at Harvard, establishing a reproducible framework for translating molecular imaging innovations directly from the bench to the bedside. For over two decades, Dr. Choi has pioneered technologies designed to bridge the gap between laboratory discovery and clinical application. His career is defined by creating tissue-specific agents that improve the diagnosis and treatment of complex human diseases, including cancers, neurodegenerative conditions, and infectious diseases. Dr. Choi is widely recognized for developing targeted theranostic probes and next-generation optical imaging systems. His invention of the FIAT-L™ system represents a landmark achievement in image-guided surgery, providing clinicians with real-time, high-resolution visualization. A prolific researcher and innovator, Dr. Choi has authored more than 250 peer-reviewed publications and is a co-founder of Nawoo Vision and Ferrex Therapeutics. His contributions have been recognized with numerous accolades, including the Johnson & Johnson Innovation Award, the Distinguished Investigator Award, and the Boston Biomedical Innovation Center Drive Award. Dr. Choi continues to push the boundaries of bioengineering, focusing on the future of precision medicine and intelligent nanocarriers that promise to redefine the standard of care worldwide.