Cognitive improvement effect of gintonin might be associated with blood-brain barrier permeability enhancement: dynamic contrast-enhanced MRI pilot study

Transl Clin Pharmacol. 2021 Mar;29(1):21-32. doi: 10.12793/tcp.2021.29.e2. Epub 2021 Mar 10.

Abstract

Along with the multiple neuroprotective effect, recent studies suggest that gintonin might increase the blood brain barrier permeability. We evaluated the effect of gintonin on the vascular permeability changes in different brain segments, using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). In this 8-week, randomized, open label pilot study, ten participants with subjective memory impairment but preserved cognitive function assigned to gintonin-enriched fraction (GEF) 300 mg/day or placebo groups. Korean versions of the Alzheimer's disease assessment scale (ADAS-K) and DCE-MRI parameters including Ktrans and Vp in different brain segments were evaluated at baseline and at 8 weeks after treatment. Nine participants completed the study protocol. No adverse events occurred during the observation period for 8 weeks in both groups. Following gintonin administration, increment trends of the brain permeability that did not reach a statistical significance were observed in the left hippocampus (Ktrans and Vp, both, p = 0.062), left thalamus and in left putamen (Ktrans, p = 0.062), and left insula and right amygdala (Vp, p = 0.062), but not in the control placebo group. The increment of the Ktrans value in the left thalamus from the baseline was highly correlated with the change of the ADAS scores (r = -0.900, p = 0.037). Gintonin might enhance the blood-brain barrier (BBB) permeability in the brain structures involved in cognitive functions. Further efficacy exploration for the synergistic effect of gintonin's BBB permeability enhancement to its other cognitive enhancing mechanisms are warranted.

Trial registration: Clinical Research Information Service Identifier: KCT0003418.

Keywords: Brain Permeability; Cognitive Dysfunction; Gintonin; Subjective Memory Impairment.