• Journal of Ginseng Research
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• v.42 no.3
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• pp.379-388
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• 2018

Background: Ginsenosides are the main ingredients of Korean Red Ginseng. They have extensively been studied for their beneficial value in neurodegenerative diseases such as Parkinson's disease (PD). However, the multitarget effects of Korean Red Ginseng extract (KRGE) with various components are unclear. Methods: We investigated the multitarget activities of KRGE on neurological dysfunction and neurotoxicity in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. KRGE (37.5 mg/ kg/day, 75 mg/kg/day, or 150 mg/kg/day, per os (p.o.)) was given daily before or after MPTP intoxication. Results: Pretreatment with 150 mg/kg/day KRGE produced the greatest positive effect on motor dysfunction as assessed using rotarod, pole, and nesting tests, and on the survival rate. KRGE displayed a wide therapeutic time window. These effects were related to reductions in the loss of tyrosine hydroxylase-immunoreactive dopaminergic neurons, apoptosis, microglial activation, and activation of inflammatory factors in the substantia nigra pars compacta and/or striatum after MPTP intoxication. In addition, pretreatment with KRGE activated the nuclear factor erythroid 2-related factor 2 pathways and inhibited phosphorylation of the mitogen-activated protein kinases and nuclear factor-kappa B signaling pathways, as well as blocked the alteration of blood-brain barrier integrity. Conclusion: These results suggest that KRGE may effectively reduce MPTP-induced neurotoxicity with a wide therapeutic time window through multitarget effects including antiapoptosis, antiinflammation, antioxidant, and maintenance of blood-brain barrier integrity. KRGE has potential as a multitarget drug or functional food for safe preventive and therapeutic strategies for PD.

• Journal of Pharmaceutical Investigation
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• v.30 no.2
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• pp.99-105
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• 2000

This study compared the permeability of $[^3H]taurine,\;[^3H]phenylalanine,\;and\;[^3H]oxytocin$ through the blood-brain barrier (BBB) in mice and rats with common carotid artery perfusion (CCAP) method that modified internal carotid artery perfusion (ICAP) method. External carotid artery (ECA) was cannulated with coagulating pterygopalatine artery (PPA) in ICAP method, while CCA was cannulated without coagulating PPA in CCAP method. Also, for evaluation of BBB permeability of drugs in mice and rats, we used intravenous injection technique. The results of CCAP method in mice at a perfusion flow-rate of 2 ml/min, the brian volume of distribution $(V_D)$ of $[^{14}C]sucrose,\;[^3H]taurine,\;[^3H]phenylalanine,\;and\;[^3H]oxytocin$ were similar to the result of ICAP method in rats at perfusion flow rate of 4 ml/min. The area under the plasma concentration-time curve and brain uptake of $[^3H]taurine$ by intravenous injection technique, were $65.5{\pm}9.7%ID^*min/ml\;and\;0.515{\pm}0.093%ID/g$, respectively, in mice, and the corresponding values were $8.00{\pm}0.03%ID^*min/ml\;and\;0.052{\pm}0.003%ID/g$ in rats. But the BBB permeability surface-area product of $[^3H]taurine$ was similar between mice and rats. In conclusion, the CCAP method in mice was simple, fast and comparable to ICAP method in rats for drug permeability through the BBB.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.1
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• pp.47-57
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• 2022

Stiripentol is an anti-epileptic drug for the treating of refractory status epilepticus. It has been reported that stiripentol can attenuate seizure severity and reduce seizure-induced neuronal damage in animal models of epilepsy. The objective of the present study was to investigate effects of post-treatment with stiripentol on cognitive deficit and neuronal damage in the cornu ammonis 1 (CA1) region of the hippocampus proper following transient ischemia in the forebrain of gerbils. To evaluate ischemia-induced cognitive impairments, passive avoidance test and 8-arm radial maze test were performed. It was found that post-treatment with stiripentol at 20 mg/kg, but not 10 or 15 mg/kg, reduced ischemia-induced memory impairment. Transient ischemia-induced neuronal death in the CA1 region was also significantly attenuated only by 20 mg/kg stiripentol treatment after transient ischemia. In addition, 20 mg/kg stiripentol treatment significantly decreased ischemia-induced astrocyte damage and immunoglobulin G leakage. In brief, stiripentol treatment after transient ischemia ameliorated transient ischemia-induced cognitive impairment in gerbils, showing that pyramidal neurons were protected and astrocyte damage and blood brain barrier leakage were significantly attenuated in the hippocampus. Results of this study suggest stiripentol can be developed as a candidate of therapeutic drug for ischemic stroke.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.199.2-200
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• 2003

Choline is an important membrane phospholipid constituent and a neurotransmitter precursor that is minimally synthesized in brain. The long-term maintenance of brain choline concentration is dependent on choline transport from plasma, which occurs via saturable transport system at the blood-brain barrier. In the present study, we examined to elucidate the characteristics of transport of cationic amines, especially choline which is one of cationic amines, to BBS using conditionally immortalized rat brain capillary endothelial cell line (TR-BBB) in vitro. (omitted)

• Biomolecules & Therapeutics
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• v.10 no.1
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• pp.37-42
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• 2002

Brain drug targeting through the blood-brain barrier (BBB) in vivo is possible with peptidornirnetic monoclonal antibodies that undergo receptor-mediated transcytosis through the BBB. Monoclonal antibody to the rat transferrin receptor, such as the OX26 was studied in rats as a transport vector through BBB on the transferrin receptor. But, OX26 is not an effective brain delivery vector in mouse. In the present studies, rat monoclonal antibody, 8D3 to the mouse transferrin receptor were evaluated for brain drug targeting vector intransgenic mouse model. Pharrnacokinetic parameters in plasma and organ uptakes were determined at varioustimes after i.v. bolus injection of [$^{}125}I$] 8D3 in Balb/c mice. Brain uptake of [$^{}125}I$] 8D3 was also studied with an internal carotid artery perfusioncapillary depletion method. After i.v. injection of [$^{}125}I$] 8D3, plasma concentrations declined biexponentially with elimination half lift of approximately 2.2 hours. Brain uptake of [$^{}125}I$] 8D3 was $0.50{\pm}0.09$ persent of injected dose per g brain after 2 hours i.v. injection. After perfusion 5 min the apparent volume of distibution of [$^{}125}I$] 8D3 in brain was $22.3 {\mu}l/g,$ which was 4.8 fold higher than the intravascular volume. These studies indicate rat monoclonal antibody to the mouse transferrin receptor, 8D3 may be used for brain drug targeting vector in mice.

• Herbal Formula Science
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• v.9 no.1
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• pp.11-34
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• 2001

1. Crinical applicational of Sagoonjatang are frequently used in internal disease, G.I.T(Gastro Intestianl Tract) disease, chronical fatigue, athma, etc. 2. Sagoonjatang adjacent prescriptions in pathological organs are the stomach, the spleen, the kidneys, the heart, the lungs. 3. Sagoonjatang partake chronic fatigue disease, G.I.T disease, pulmonary disease, brain blood barrier disease, infertility, vomiting of pregnancy, sedation of brain, healing mechanism, sweating regulation, urination, peripheral blood ciraculation, electrolyte blance, etc.

• Biomolecules & Therapeutics
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• v.18 no.1
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• pp.65-70
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• 2010

The blood-brain barrier (BBB) transport of acetylcholinesterase (AChE) inhibitors, donepezil and tacrine suggested to be mediated by choline transport system in our previous study. Therefore, in the present study, we investigated the interaction of other AChE inhibitors, rivastigmine and galantamine with choline transporter at the BBB. The effects of rivastigmine and galantamine on the transport of choline by conditionally immortalized rat brain capillary endothelial cell lines (TR-BBB cells) were characterized by cellular uptake study using radiolabeled choline. The uptake of [$^3H$]choline was inhibited by rivastigmine and galantamine, with $IC_{50}$ values (i.e. concentration necessary for 50% inhibition) for 1.13 and 1.15 mM, respectively. Rivastigmine inhibited the uptake of [$^3H$]choline competitively with $K_i$ of 1.01 mM, but galantamine inhibited noncompetitively. In addition, the efflux of [$^3H$]choline was significantly inhibited by rivastigmine and galantamine. Our results indicated that the BBB choline transporter may be involved in a part of the influx and efflux transport of rivastigmine across the BBB. These findings should be therapeutically relevant to the treatment of Alzheimer's disease (AD) with AChE inhibitors, and, more generally, to the BBB transport of CNS-acting cationic drugs via choline transporter.

• Biomolecules & Therapeutics
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• v.5 no.1
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• pp.53-58
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• 1997

$[Lys^7$]dermorphin, abbreviated K7DA, which has structural features similar to a metabolically stable $\mu$-opioid peptide agonist $[D-Arg^2, Lys^4$]dermorphin analogue (DALDA), but is intrinsically more potent with respect to binding to the $\mu$-opioid peptide receptor. The present studies report on attempts to enhance brain uptake of systemically administered K7DA by conjugation to a complex of streptavidin (SA) and the OX26 murine monoclonal antibody to the rat transferrin receptor, which undergoes receptor-mediated transcytosis through the blood-brain barrier (BBB). SA-OX26 conjugate mediates BBB transport of biotinylated therapeutics. The K7DA is monobiotinylated at the $\varepsilon$-amino group of the $[Lys^7$] residue with cleavable linker using NHS-SS-biotin. The brain uptake of $^{125}I$ labeled biotinylated K7DA ($^{125}I$-bio-SSa-K7DA) was very small and rapidly metabolized after intravenous injection. The brain uptake, expressed as percent of injected dose delivered per gram of brain, of the $^{125}I$-bio-55-K7DA bound to the SA-OX26 conjugate $^{125}I$-bio-SS-K7DA/SA-OX26) was 0.14$\pm$0.01, a level that is 2-fold greater than the brain uptake of morphine. The cleavability of the disulfide linker in vivo in rat plasma and brain was assessed with gel filtration HPLC and intravenous injection of labeled opioid chimeric peptides. The disulfide linker is stable in plasma in vivo but is cleaved in rat brain in vivo. In conclusion, these studies show that delivery of these potential opioid peptides to the brain may be improved by coupling them to vector-mediated BBB drug delivery system.

• Korean Journal of Environmental Biology
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• v.24 no.2 s.62
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• pp.166-171
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• 2006

To elucidate the effect of phytoestrogens on the prevention of neurodegenerative disease in postmenopausal women, the expression of occludin which build up the blood-brain barrier was examined in hippocampus following oral administration of estrogen (E2), genistein, diadzein or combination of genistein and diadzein in ovariectomized (OVX) female rats. E2 significantly increased occludin mRNA level in OVX rat hippocampus, suggesting that estrogen is a physiological regulator for structural integrity of the blood-brain barrier in hippocampus. Following isoflavone diet for 4 weeks, there was significant increase in occludin mRNA level in hippocampus, suggesting that isoflavone diet may be effective for protection of structural integrity of blood-brain barrier in hippocampus from degenerative changes in estrogen deficiency.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.154-155
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• 1998

Taurine, 2-aminoethanesulfonic acid is widely distributed in animal tissues and has a variety of biological activities. A recent worldwide study demonstrated beneficial effects of taurine on aging and age-associated disorders. In general, taurine levels in the brain decrease when an animal is subjected to pathologic conditions such as ischemia-anoxia and seizure. But taurine levels tend to increase in the brain in hypertention. In the present study, the blood-brain barrier BBB) transport of [$^3$H]taurine was compared between spontaneously hypertensive rats (SHR) and normotensive Sprague-Dawley rats (SD) using Internal artery carotid perfusion (ICAP) at a rate of 4$m\ell$/min for 10, 15 and 30 second. Calculated V$\_$D/, volume of distribution in brain, and PS, the permeability surface area product of [$^3$H]taurine through the BBB in SHR was a little lower than that in SD. PS for 15s is more higher than that of other seconds in both of them. It could be followed by taurine efflux back into blood after 15s. We also obtained pharmacokinetic parameters using intravenous injection of plasma volume marker, [$\^$14/C]sucrose and [$^3$H] taurine. PS value of [$^3$H]taurine in SHR (16.1 ${\pm}$ 2.9 ${\times}$ 10$\^$-3/ $m\ell$/min/g) was significantly higher than that in SD (7.4 ${\pm}$ 0.8 ${\times}$ 10$\^$-3/ $m\ell$/min/g). There is also significant difference for %ID/g in brain between SHR (0.195 ${\pm}$ 0.031) and SD (0.058 ${\pm}$ 0.003).