Ginseng gintonin attenuates the disruptions of brain microvascular permeability and microvascular endothelium junctional proteins in an appswe/psen‑1 double‑transgenic mouse model of Αlzheimer's disease

Abstract

It has been previously indicated that gintonin, which is a novel exogenous ginseng-derived lysophosphatidic acid (LPA) receptor ligand, restores memory dysfunctions in an APPswe/PSEN-1 double-transgenic mouse model of Alzheimer's disease (AD Tg mice) by attenuating β-amyloid plaque deposition, recovering cholinergic dysfunctions and upregulating hippocampal neurogenesis in the cortex and hippocampus. Although β-amyloid plaque depositions in AD is accompanied with disruptions of brain microvessels, including the brain-blood barrier (BBB), it is unknown whether gintonin exerts protective effects on brain microvascular dysfunctions in AD Tg mice. In the present study, the effects of gintonin-enriched fraction (GEF) on the changes in β-amyloid plaque depositions, brain permeability of Evans blue, and microvascular junctional proteins were investigated in AD Tg mice. Long-term oral administration of GEF reduced β-amyloid plaque depositions in the cortex and hippocampus of AD Tg mice. GEF treatment also reduced the permeability of Evans blue through BBB and decreased immunoreactivity of platelet endothelial cell adhesion molecule-1 (a marker of BBB disruption) in the cortex and hippocampus of AD Tg mice in a dose-dependent manner. However, GEF elevated the protein expression of occludin, claudin-5 and zonula occludens-1, which are tight-junction proteins. The present results demonstrated that long-term oral GEF treatment not only attenuates β-amyloid plaque depositions in the brain but also exhibits protective effects against microvascular disruptions in AD Tg mice. Finally, GEF exhibits anti-AD effects through attenuation of β-amyloid plaque depositions and protection against brain microvascular damage in an AD animal model.

Emerging evidence that ginseng components improve cognition in subjective memory impairment, mild cognitive impairment, and early Alzheimer's disease dementia

“…Furthermore, if we consider the use of KRGM gintonin, the treatment would be both cost-effective and economical [ 59 ]. Additionally, ginseng gintonin opens BBB transiently via LPA1/3 receptors and increases brain permeability in vitro and in vivo studies [ [62] , [63] , [64] ], with gintonin demonstrating the capacity to maintain BBB integrity disrupted by Aβ in AD animal mouse models [ 65 ]. Ginseng gintonin transiently opens the BBB and enhances the permeability of donepezil, an AD medicine, by 30% in rats, along with 70 kDa high molecular weight dextrin [ 62 ].…”

Applications of Phyto-Nanotechnology for the Treatment of Neurodegenerative Disorders

“…Table 3 summarizes the miRNAs used for treatment of neurological disorders. [143,144] miRNA-107 Overexpressed APP cells Mice brain tissue-APP/PS1 [143] miRNA-101a-3p [143] AGR-GRg1 miRNA-873-5p Mouse Hippocampus [145] L-Dopa miRNA-30b-5p, miRNA-30a-5p Plasma PD [146] miRNA-29a-3p, miRNA-30b-5p, miRNA-103a-3p…”

Antioxidants in Alzheimer’s Disease: Current Therapeutic Significance and Future Prospects

“…Recent findings suggest that treatment with gintonin in AD results in improved synaptic and memory functions in the brain [ 176 ]. It reflects an emerging role as a modulator of neurogenesis and synaptic transmission, and it has the potential to regulate autophagy in primary cortical astrocytes [ 176 , 177 ]. Moreover, as a novel agonist of lysophosphatidic acid receptors, gintonin regulated several GPCR, including GPR55 and GPR40 [ 177 ].…”

“…It reflects an emerging role as a modulator of neurogenesis and synaptic transmission, and it has the potential to regulate autophagy in primary cortical astrocytes [ 176 , 177 ]. Moreover, as a novel agonist of lysophosphatidic acid receptors, gintonin regulated several GPCR, including GPR55 and GPR40 [ 177 ]. Nevertheless, further exploration is still required to understand gintonin’s underlying mode of action in AD.…”