• The Korean Journal of Physiology
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• v.29 no.1
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• pp.61-67
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• 1995

The extract of Ginkgo bibloba (EGb) is a complex mixture of natural products from the Ginkgo leaves and clinically used for the treatment of cerebral and peripheral circulatory disturbances due to its combined activity of several vasoactive principles. In this study we investigated the action of EGb and its mechanism in isolated rabbit corporal smooth muscle to evaluate the possibility of using this material as a pharmacoerecting agent. Strips of rabbit corpus cavernosum were mounted in organ chambers to measure isometric tension. EGb began to exert an relaxing effect at 1 mg/ml in the submaximally precontracted muscle strips with phenylephrine $(PHE,\;5{\times}10^{-6}\;M)$; causing concentration-dependent relaxation with maximal effect at $3{\sim}5\;mg/ml$. That relaxation was partially inhibited by removal of the smooth muscle endothelium or by pretreatment with a NO scavenger, pyrogallol $(10^{-4}\;M)$ or the guanylate cyclase inhibitor, methylene blue $(10^{-4}\;M)$. Pretreatment with EGb (3 mg/ml) inhibited PHE- $(5{\times}10^{-6}\;M)$ or KCI- (20 and 40 mM) induced contraction of muscle strip. In calcium-free high potassium solution EGb depressed the basal tone of the depolarized muscle strip and inhibited calcium-induced contraction when $CaCl_2$ $(10^{-4}\;M)$ was added. These results suggest that EGb relaxes rabbit corpus cavernosal smooth muscle through multiple action mechanisms that include increasing the release of nitric oxide from the corporal sinusoidal endothelium, sequestration of intracytosolic calcium, and maybe a hyperpolarizing action.

• Parasites, Hosts and Diseases
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• v.59 no.3
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• pp.189-225
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• 2021

The use of albendazole and mebendazole, i.e., benzimidazole broad-spectrum anthelmintics, in treatment of parasitic infections, as well as cancers, is briefly reviewed. These drugs are known to block the microtubule systems of parasites and mammalian cells leading to inhibition of glucose uptake and transport and finally cell death. Eventually they exhibit ovicidal, larvicidal, and vermicidal effects on parasites, and tumoricidal effects on hosts. Albendazole and mebendazole are most frequently prescribed for treatment of intestinal nematode infections (ascariasis, hookworm infections, trichuriasis, strongyloidiasis, and enterobiasis) and can also be used for intestinal tapeworm infections (taeniases and hymenolepiasis). However, these drugs also exhibit considerable therapeutic effects against tissue nematode/cestode infections (visceral, ocular, neural, and cutaneous larva migrans, anisakiasis, trichinosis, hepatic and intestinal capillariasis, angiostrongyliasis, gnathostomiasis, gongylonemiasis, thelaziasis, dracunculiasis, cerebral and subcutaneous cysticercosis, and echinococcosis). Albendazole is also used for treatment of filarial infections (lymphatic filariasis, onchocerciasis, loiasis, mansonellosis, and dirofilariasis) alone or in combination with other drugs, such as ivermectin or diethylcarbamazine. Albendazole was tried even for treatment of trematode (fascioliasis, clonorchiasis, opisthorchiasis, and intestinal fluke infections) and protozoan infections (giardiasis, vaginal trichomoniasis, cryptosporidiosis, and microsporidiosis). These drugs are generally safe with few side effects; however, when they are used for prolonged time (>14-28 days) or even only 1 time, liver toxicity and other side reactions may occur. In hookworms, Trichuris trichiura, possibly Ascaris lumbricoides, Wuchereria bancrofti, and Giardia sp., there are emerging issues of drug resistance. It is of particular note that albendazole and mebendazole have been repositioned as promising anti-cancer drugs. These drugs have been shown to be active in vitro and in vivo (animals) against liver, lung, ovary, prostate, colorectal, breast, head and neck cancers, and melanoma. Two clinical reports for albendazole and 2 case reports for mebendazole have revealed promising effects of these drugs in human patients having variable types of cancers. However, because of the toxicity of albendazole, for example, neutropenia due to myelosuppression, if high doses are used for a prolonged time, mebendazole is currently more popularly used than albendazole in anti-cancer clinical trials.

• Nutrition Research and Practice
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• v.16 no.2
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• pp.173-193
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• 2022

BACKGROUND/OBJECTIVES: Alzheimer's disease (AD) is one of the most representative neurodegenerative disease mainly caused by the excessive production of amyloid beta (Aβ). Several studies on the antioxidant activity and protective effects of Populus tomentiglandulosa (PT) against cerebral ischemia-induced neuronal damage have been reported. Based on this background, the present study investigated the protective effects of PT against cognitive impairment in AD. MATERIALS/METHODS: We orally administered PT (50 and 100 mg/kg/day) for 14 days in an Aβ_25-35-induced mouse model and conducted behavioral experiments to test cognitive ability. In addition, we evaluated the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum and measured the production of lipid peroxide, nitric oxide (NO), and reactive oxygen species (ROS) in tissues. RESULTS: PT treatment improved the space perceptive ability in the T-maze test, object cognitive ability in the novel object recognition test, and spatial learning/long-term memory in the Morris water-maze test. Moreover, the levels of AST and ALT were not significantly different among the groups, indicating that PT did not show liver toxicity. Furthermore, administration of PT significantly inhibited the production of lipid peroxide, NO, and ROS in the brain, liver, and kidney, suggesting that PT protected against oxidative stress. CONCLUSIONS: Our study demonstrated that administration of PT improved Aβ_25-35-induced cognitive impairment by regulating oxidative stress. Therefore, we propose that PT could be used as a natural agent for AD improvement.

• Herbal Formula Science
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• v.30 no.4
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• pp.293-304
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• 2022

Objectives : Sagunja-Tang is a famous prescription used in Korean medicine for the purpose of promoting vital energy, and there are few studies using Sagunja-Tang on cerebrovascular diseases yet. As previous studies confirmed that Sagunja-tang is highly likely to be used effectively for stroke, this study was intended to predict the mechanism through which Sagunja-tang would act effectively on stroke. Methods : In this study, a network pharmacology analysis method was used, and oral bioavailability (OB), drug likeness (DL), Caco-2 and BBB permeability were utilized to select compounds with potential activity. For the values of each variable used in this study, OB ≥ 30%, DL ≥ 0.18, Caco-2 ≥ 0, and BBB ≥ 0.3 were applied. Using the above variables, the relations between target genes and diseases that are presumed to be involved in the selected bioavailable compounds were constructed in a network format, and proteins thought to play a major role were identified. Results : Among the compounds included in Sagunja-Tang, 26 bioavailable compounds were selected and it was confirmed that these compounds can be effectively used in cerebrovascular diseases such as Alzheimer's disease and stroke. These compounds are considered to act on proteins related in cell death and growth. The most important mechanism of action was predicted to be apoptosis, and the protein that is thought to play the most key action in this mechanism was caspase-3. Conclusions : In our future study, Sagunja-Tang will be used in an ischemic stroke mouse model, and the mechanism of action will be explored focusing on apoptosis and cell proliferation.

• Journal of Ginseng Research
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• v.47 no.2
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• pp.274-282
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• 2023

Background: Ginsenoside compound K (CK) stimulated activation of the PI3K-Akt signaling is one of the major mechanisms in promoting cell survival after stroke. However, the underlying mediators remain poorly understood. This study aimed to explore the docking protein of ginsenoside CK mediating the neuroprotective effects. Materials and methods: Molecular docking, surface plasmon resonance, and cellular thermal shift assay were performed to explore ginsenoside CK interacting proteins. Neuroscreen-1 cells and middle cerebral artery occlusion (MCAO) model in rats were utilized as in-vitro and in-vivo models. Results: Ginsenoside CK interacted with recombinant human PTP1B protein and impaired its tyrosine phosphatase activity. Pathway and process enrichment analysis confirmed the involvement of PTP1B and its interacting proteins in PI3K-Akt signaling pathway. PTP1B overexpression reduced the tyrosine phosphorylation of insulin receptor substrate 1 (IRS1) after oxygen-glucose deprivation/reoxygenation (OGD/R) in neuroscreen-1 cells. These regulations were confirmed in the ipsilateral ischemic hemisphere of the rat brains after MCAO/R. Ginsenoside CK treatment reversed these alterations and attenuated neuronal apoptosis. Conclusion: Ginsenoside CK binds to PTP1B with a high affinity and inhibits PTP1B-mediated IRS1 tyrosine dephosphorylation. This novel mechanism helps explain the role of ginsenoside CK in activating the neuronal protective PI3K-Akt signaling pathway after ischemia-reperfusion injury.

• The Korean Journal of Pain
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• v.36 no.4
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• pp.408-424
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• 2023

Central post-stroke pain (CPSP) is an incapacitating disorder that impacts a substantial proportion of stroke survivors and can diminish their quality of life. Conventional therapies for CPSP, including tricyclic antidepressants, anticonvulsants, and opioids, are frequently ineffective, necessitating the investigation of alternative therapeutic strategies. Repetitive transcranial magnetic stimulation (rTMS) is now recognized as a promising noninvasive pain management method for CPSP. rTMS modulates neural activity through the administration of magnetic pulses to specific cortical regions. Trials analyzing the effects of rTMS on CPSP have generated various outcomes, but the evidence suggests possible analgesic benefits. In CPSP and other neuropathic pain conditions, high-frequency rTMS targeting the primary motor cortex (M1) with figure-eight coils has demonstrated significant pain alleviation. Due to its associaton with analgesic benefits, M1 is the most frequently targeted area. The duration and frequency of rTMS sessions, as well as the stimulation intensity, have been studied in an effort to optimize treatment outcomes. The short-term pain relief effects of rTMS have been observed, but the long-term effects (> 3 months) require further investigation. Aspects such as stimulation frequency, location, and treatment period can influence the efficacy of rTMS and ought to be considered while planning the procedure. Standardized guidelines for using rTMS in CPSP would optimize therapy protocols and improve patient outcomes. This review article provides an up-to-date overview of the incidence, clinical characteristics, outcome of rTMS in CPSP patients, and future perspective in the field.

• Journal of Veterinary Clinics
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• v.40 no.1
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• pp.56-61
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• 2023

A 5-month-old female domestic short-haired cat presented with a history of seizure episodes for two months following an animal bite injury to the head. There were no remarkable findings on physical and neurological examination or blood analysis. Computed tomography revealed a fracture of the left parietal bone with an inward displacement of the bone fragment while magnetic resonance imaging revealed an enlarged temporal horn of the left lateral ventricle and a pseudomeningocele compressing the adjacent cerebral parenchyma. Subsequently, cerebrospinal fluid analysis results were normal. The patient was diagnosed with traumatic brain injury (TBI), with subsequent post-traumatic hydrocephalus (PTH) and pseudomeningocele. Despite treatment with phenobarbital and levetiracetam, seizures were not sufficiently controlled. Craniectomy for bone fragment removal and duraplasty were performed after a week. The patient then returned to normal condition with no further seizure activity. On repeated MRI two months after discharge, the hydrocephalus of the lateral ventricle and pseudomeningocele were enlarged; however, the patient maintained a good clinical status without any neurological signs. To the best of our knowledge, PTH and intracranial pseudomeningoceles have not yet been reported in cats. PTH and pseudomeningocele are among the complications of TBI and may not have any significant relevance with the clinical signs in this case. Thus, to broaden our knowledge about PTH and pseudomeningocele in cats, we describe serial changes in the clinical findings of this cat over the treatment period.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2020.08a
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• pp.76-76
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• 2020

Stachys sieboldii Miq. (chinese artichoke), which has been extensively used in oriental traditional medicine to treat of ischemic stroke; however, the role of Stachys sieboldii Miq. (SSM) in cerebral ischemia/reperfusion (I/R) injury is not yet fully understood. In the current study, the neuroblastoma cell line (SH-SY5Y) were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) to simulate I/R injury in vitro model. The results showed that SSM improved OGD/R-induced inhibitory effect on cell viability of SH-SY5Y Cells. SSM displayed anti-oxidative activity as proved by the decreased levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and increased activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in OGD/R-induced SH-SY5Y Cells. In addition, cell apoptosis was markedly decreased after SSM treatment in OGD/R-induced SH-SY5Y Cells. The up-regulation of Bcl-2 and down-regulation of Bax, thus reducing the Bax/Bcl-2 ratio that in turn protected the activation of caspase-9 and -3, and inhibition of poly (ADP-ribose) polymerase cleavage, which was associated with the blocking of cytochrome c release to the cytoplasm. Collectively, SSM protected human neuroblastoma SH-SY5Y cells from OGD/R-induced injury via preventing mitochondrial-dependent pathway through scavenging excessive ROS, suggesting that SSM might be a potential agent for the ischemic stroke therapy.

• Investigative Magnetic Resonance Imaging
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• v.3 no.2
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• pp.173-178
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• 1999

Purpose : To evaluate the usefulness of functional MRI (fMRI) of visual cortex in patients with ischemic infarction in the occipital lobe. Materials and Methods : Four patients with the symptoms and signs of visual cortical ischemia were included. Functional MRI was performed by 2D-FLASH technique with the parameter of 90/56msec TR/TE, $40^{\circ}$ flip angle, $240{\times}240{\;}FOV,{\;}64{\times}128$ matrix number, 8.32 seconds acquisition time, 8mm slice thickness. An axial slice including both visual cortices was selected and alternative activation and resting of the visual cortex was performed using red color photostimulator. all patients undertook visual field test, and vascular abnormality was examined by MRA (n=4) and DSA (n=2). fMRI results were compared with the results of a visual field test, conventional MRI and cerebral angiography. Results : On fMRI, decreased activity of the visual cortex was found in the occipital lobe corresponding to stenosis of the posterior cerebral artery or its branch noted on angiogram. However, 2 of 4 patients showed no abnormal findings on conventional MRI. Visual field defect was noted in 3 patients, one and of whom showed no abnormality on conventional MRI and diffusion-weighted image, but revealed decreased activity in the corresponding visual cortex on fMRI. Conclusion : fMRI may be a sensitive method for detection of the status of decreased blood flow or vascular reserve which other methods can not.

• The Korean Journal of Zoology
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• v.29 no.3
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• pp.215-233
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• 1986

The effect of tryptophan on brain formation at the early stage of chick embryo has been investigated morphologically using electron microscope. The electron micrographs of cerebral cortex cells of $5\\sim10$ day old chick embryo, which received 1.0mg of tryptophan showed that the irregularity, evagination and disruption of nuclear membrane and nuclear chromatin condensation, nucleolar chromatin margination and segragation. Hypertrophy of stalks, vesicles, and vacuoles can be seen and dilation and vesiculation of rough endoplamic reticulum and polysome disaggregation occured. Protein and RNA levels and the activity of several enzymes such as lactate dehydrogenase, succinate dehydrogenase, malate dehydrogenase and glucose 6-phosphate dehydrogenase of tryptophan administered group were significantly lower than those of control group suggesting that the tryptophan administration depressed protein biosynthesis resulting in the decrease of enzyme activity. It was found that serotonin content of egg yolk which has been incubated for 10 days were as much as three times that of control egg yolk. It is not clear whether the increase of serotonin content might inhibit intracellular yolk granule degradation which might result in malformation of chick embryo, but it is likely that tryptophan administration might depress protein biosynthesis, consequently, the enzyme biosynthesis would be impaired. This might give rise to improper development of chick embryo.