• Journal of Life Science
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• v.32 no.7
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• pp.550-566
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• 2022

Stroke is among the leading causes of death and long-term physical and cognitive disabilities worldwide, affecting an estimated 15 million people annually. The pathophysiological process of stroke is complicated by multiple and coordinated events. The breakdown of the blood-brain barrier (BBB) in people with stroke can significantly contribute to the development of ischemic brain injury. Therefore, BBB disruption is recognized as a hallmark of stroke; thus, it is important to develop novel therapeutic strategies that can protect against BBB dysfunction in ischemic stroke. Traditional medicines are composed of natural products, which represent a promising source of new ingredients for the development of conventional medicines. Indeed, several studies have shown the effectiveness of Korean medicine on stroke, highlighting the value of Korean medicinal treatment for ischemic stroke. This review summarizes the current information and underlying mechanisms regarding the ameliorating effects of the formula, decoction, herbs, and active components of traditional Korean medicine on cerebral ischemia-induced BBB disruption. These traditional medicines were shown to have protective effects on the BBB in many cellular and animal ischemia models of stroke, and experiments in various animal species, such as mice and rats. In addition, they showed brain-protective effects by protecting the BBB through the regulation of tight junction proteins and matrix metalloproteinase-9, reducing edema, neuroinflammation, and neuronal cell death. We hope that this review will help promote further investigation into the neuroprotective effects of traditional Korean medicines and stimulate the performance of clinical trials on Korean herbal medicine-derived drugs in patients with stroke.

• Journal of Korean Neurosurgical Society
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• v.65 no.6
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• pp.790-800
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• 2022

Objective : EID3 (EP300-interacting inhibitor of differentiation) was identified as a novel member of EID family and plays a pivotal role in colorectal cancer development. However, its role in glioma remained elusive. In current study, we identified EID3 as a novel oncogenic molecule in human glioma and is critical for glioma cell survival, proliferation and invasion. Methods : A total of five patients with glioma were recruited in present study and fresh glioma samples were removed from patients. Four weeks old male non-obese diabetic severe combined immune deficiency (NOD/SCID) mice were used as transplant recipient models. The subcutaneous tumor size was calculated and recorded every week with vernier caliper. EID3 and AMP-activated protein kinase α1 (AMPKα1) expression levels were confirmed by real-time polymerase chain reaction and Western blot assays. Colony formation assays were performed to evaluate cell proliferation. Methyl thiazolyl tetrazolium (MTT) assays were performed for cell viability assessment. Trypan blue staining approach was applied for cell death assessment. Cell Apoptosis DNA ELISA Detection Kit was used for apoptosis assessment. Results : EID3 was preferentially expressed in glioma tissues/cells, while undetectable in astrocytes, neuronal cells, or normal brain tissues. EID3 knocking down significantly hindered glioma cell proliferation and invasion, as well as induced reduction of cell viability, apoptosis and cell death. EID3 knocking down also greatly inhibited tumor growth in SCID mice. Knocking down of AMPKα1 could effectively rescue glioma cells from apoptosis and cell death caused by EID3 absence, indicating that AMPKα1 acted as a key downstream regulator of EID3 and mediated suppression effects caused by EID3 knocking down inhibition. These findings were confirmed in glioma cells generated patient-derived xenograft models. AMPKα1 protein levels were affected by MG132 treatment in glioma, which suggested EID3 might down regulate AMPKα1 through protein degradation. Conclusion : Collectively, our study demonstrated that EID3 promoted glioma cell proliferation and survival by inhibiting AMPKα1 expression. Targeting EID3 might represent a promising strategy for treating glioma.

• The Korea Journal of Herbology
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• v.36 no.6
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• pp.1-8
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• 2021

Objectives : Atractylodis rhizoma Alba has been traditionally used as a medicinal resource that is used for enhancing Qi (氣) in traditional medicine in Korea, China, and Japan. This study investigated the protective effects of Atractylodis rhizoma Alba extract (ARE) against trimethyltin (TMT), a neurotoxin that causes selective hippocampal injury, using both in vitro and in vivo models. Methods : We investigated the effects of ARE on TMT- (5mM) induced cytotoxicity in primary cultures of mouse hippocampal cells (7 days in vitro ) and on hippocampal injury in C57BL/6 mice injected with TMT (2.6 mg/kg). Results : We observed that ARE treatment (0 - 50 ㎍/mL) significantly reduced TMT-induced cytotoxicity in cultured hippocampal neurons in a dose-dependent manner, based on results of lactate dehydrogenase and 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assays. Additionally, this study showed that orally administered ARE (5 mg/kg; between -6 and 0 days before TMT injection) significantly attenuated seizures in adult mice. Furthermore, quantitative analysis of allograft inflammatory factor-1 (Iba-1)- and glial fibrillary acidic protein (GFAP)- positive cells showed significantly reduced levels of Iba-1- and GFAP-positive cell bodies in the dentate gyrus of mice treated with ARE prior to TMT injection. These findings indicate the significant protective effects of ARE against the TMT-induced massive activation of microglia and astrocytes in the hippocampus. Conclusions : We conclude that ARE minimizes the detrimental effects of TMT-induced hippocampal neurotoxicity, both in vitro and in vivo . Our findings may serve as useful guidelines to support ARE administration as a promising pharmacotherapeutic approach to hippocampal degeneration.

• Journal of Microbiology and Biotechnology
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• v.32 no.9
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• pp.1154-1167
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• 2022

In this study, we investigated the anti-amnesic effect of Korean red pine (Pinus densiflora) bark extract (KRPBE) against amyloid beta_1-42 (Aβ_1-42)-induced neurotoxicity. We found that treatment with KRPBE improved the behavioral function in Aβ-induced mice, and also boosted the antioxidant system in mice by decreasing malondialdehyde (MDA) content, increasing superoxide dismutase (SOD) activities, and reducing glutathione (GSH) levels. In addition, KRPBE improved the cholinergic system by suppressing reduced acetylcholine (ACh) content while also activating acetylcholinesterase (AChE), regulating the expression of choline acetyltransferase (ChAT), postsynaptic density protein-95 (PSD-95), and synaptophysin. KRPBE also showed an ameliorating effect on cerebral mitochondrial deficit by regulating reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and ATP levels. Moreover, KRPBE modulated the expression levels of neurotoxicity indicators Aβ and phosphorylated tau (p-tau) and inflammatory cytokines TNF-α, p-IκB-α, and IL-1β. Furthermore, we found that KRPBE improved the expression levels of neuronal apoptosis-related markers BAX and BCl-2 and increased the expression levels of BDNF and p-CREB. Therefore, this study suggests that KRPBE treatment has an anti-amnestic effect by modulating cholinergic system dysfunction and neuroinflammation in Aβ_1-42-induced cognitive impairment in mice.

• Journal of Life Science
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• v.32 no.10
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• pp.771-777
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• 2022

Dopaminergic (DA) cell death in Parkinson's disease (PD) has been attributed to multiple, distinct genetic and environmental factors. In rare familial PD loss of parkin function mutations play a key role in nigral DA neuron-specific pathogenesis primarily via endoplasmic reticulum (ER) stress. In more prevalent sporadic PD, environmental exposure to pesticides has a significant epidemiological role. However, it is largely unknown how environmental exposure to xenobiotics is etiologically linked with the known etiology in familial PD. In the present study biochemical evidence for a common pathogenic mechanism between sporadic and familial PD has been identified employing the recently characterized mesencephalic DA cell line, N27-A. Dieldrin, an organochlorine pesticide epidemiologically implicated in sporadic PD, induced the markers of ER stress response such as a chaperone BiP/Grp78, heme oxygenase-1 and especially, parkin. Accordingly, dieldrin activated the ER resident Caspase-12, a mediator of ER stress-specific apoptosis, during cell death of N27-A cells. Of great interest the dieldrin-induced DA neuronal cell death was synergistically rescued by the overexpression of ER resident neuroprotective proteins, parkin and Bcl-2. The present findings implicate that accumulation of ER stress could be one of common pathogenic mechanisms in idiopathic and familial PD, and some ER proteins, such as parkin and Bcl-2 may effectively attenuate ER stress-mediated N27-A DA cell death.

• The Korea Journal of Herbology
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• v.29 no.3
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• pp.27-33
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• 2014

Objectives : The aim of this study was to investigate the protective effect of extract of Thuja orientalis leaves (TOFE) against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity by inhibition of inflammation in in vitro and in vivo models of Parkinson's disease (PD). Methods : We evaluated the effect of TOFE against lipopolysaccharide (LPS)/1-methyl-4-phenylpyridinium ($MPP^+$) toxicity using nitric oxide (NO) assay, inducible NO synthase and cyclooxygenase 2 western blot, tyrosine hydroxylase and microglia activation immunohistochemistry (IHC) in BV2 cell, primary rat mesencephalic neurons, or C57BL/6 mice. We also evaluated the effect of TOFE in mice PD model induced by MPTP. C57BL/6 mice were treated with TOFE 50 mg/kg for 5 days and were injected intraperitoneally with four administrations of MPTP on the last day. We conducted behavioral tests and IHC analysis to see how TOFE affect MPTP-induced neuronal loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) and striatum (ST) of mice. To assess the anti-inflammation effects, we carried out glial fibrillary acidic protein and macrophage-1 antigen integrin alpha M in IHC in SNpc and ST of mice. Results : In an in vitro system, TOFE decreasesd NO generations in BV2 cells. TOFE protected dopaminergic cells against LPS or $MPP^+$-induced toxicity in primary mesencephalic dopaminergic neurons. In vivo system, TOFE at 50 mg/kg treated group showed improved motor deteriorations than the MPTP only treated group and TOFE significantly protected striatal dopaminergic damage from MPTP-induced neurotoxicity in mice. Moreover, TOFE inhibited activation of astrocyte and microglia in SNpc and ST of the mice. Conclusions : We concluded that TOFE showed anti-parkinsonian effect by protection of dopaminergic neurons against MPTP toxicity through anti-inflammatory actions.

• Journal of Korean Neurosurgical Society
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• v.65 no.5
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• pp.665-679
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• 2022

Objective : Patients with mild ischemic stroke experience various sequela and residual symptoms, such as anxious behavior and deficits in movement. Few approaches have been proved to be effective and safe therapeutic approaches for patients with mild ischemic stroke by acute stroke. Sildenafil (SIL), a phosphodiesterase-5 inhibitor (PDE5i), is a known remedy for neurodegenerative disorders and vascular dementia through its angiogenesis and neurogenesis effects. In this study, we investigated the efficacy of PDE5i in the emotional and behavioral abnormalities in rats with mild ischemic stroke. Methods : We divided the rats into four groups as follows (n=20, respectively) : group 1, naïve; group 2, middle cerebral artery occlusion (MCAo30); group 3, MCAo30+SIL-pre; and group 4, MCAo30+SIL-post. In the case of drug administration groups, single dose of PDE5i (sildenafil citrate, 20 mg/kg) was given at 30-minute before and after reperfusion of MCAo in rats. After surgery, we investigated and confirmed the therapeutic effect of sildenafil on histology, immunofluorescence, behavioral assays and neural oscillations. Results : Sildenafil alleviated a neuronal loss and reduced the infarction volume. And results of behavior task and immunofluorescence shown possibility that anti-inflammation process and improve motor deficits sildenafil treatment after mild ischemic stroke. Furthermore, sildenafil treatment attenuated the alteration of theta-frequency rhythm in the CA1 region of the hippocampus, a known neural oscillatory marker for anxiety disorder in rodents, induced by mild ischemic stroke. Conclusion : PDE5i as effective therapeutic agents for anxiety and movement disorders and provide robust preclinical evidence to support the development and use of PDE5i for the treatment of mild ischemic stroke residual disorders.

• Journal of Pharmacopuncture
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• v.25 no.3
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• pp.216-223
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• 2022

Objectives: Oxidative stress plays a key role in chronic and acute brain disorders and neuronal damage associated with Alzheimer disease (AD) and other neurodegeneration symptoms. The neuroprotective effects of berberine and Berberis vulgaris (barberry) root extract against apoptosis induced by hydrogen peroxide (H₂O₂) in the human SH-SY5Y cell line were studied. Methods: The methanolic extraction of barberry root was performed using a maceration procedure. Oxidative stress was induced in SH-SY5Y cells by H₂O₂, and an MTT assay was applied to evaluate the neuroprotective effects of berberine and barberry root extract. The cells were pretreated with the half maximal inhibitory concentration (IC₅₀) of each compound (including berberine, barberry root extract, and H₂O₂), and the anti-apoptotic effects of all components were investigated using RT-PCR. Results: The SH-SY5Y cell viability increased in both groups exposed to 75 and 150 ppm barberry extract compared with that in the H₂O₂-treated group. The data showed that exposing SH-SY5Y cells to 30 ppm berberine significantly increased the cell viability compared with the H₂O₂-treated group; treatment with 150 and 300 ppm berberine and H₂O₂ significantly decreased the SH-SY5Y cell viability and was associated with berberine cytotoxicity. The mRNA levels of Bax decreased significantly under treatment with berberine at 30 ppm compared with the control group. A significant increase in Bcl-2 expression was observed only after treatment with the IC₅₀ of berberine. The expression level of Bcl-2 in cells exposed to both berberine and barberry extracts was also significantly higher than that in cells exposed to H₂O₂. Conclusion: The outcomes of this study suggest that treatment of SH-SY5Y cells with barberry extract and berberine could suppress apoptosis by regulating the actions of Bcl-2 family members.

• Korean journal of applied entomology
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• v.61 no.1
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• pp.109-115
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• 2022

Vitellogenesis is the process by which yolk accumulates in developing oocytes. The initiation of vitellogenesis represents an important control point in oogenesis. When females of the model insect Drosophila melanogaster molt to become adults, their ovaries lack mature vitellogenic oocytes, only producing them after reproductive maturation. After maturation, vitellogenesis stops until a mating signal re-activates it. Juvenile hormone (JH) from the endocrine organ known as the corpora allata (CA) is the major insect gonadotropin that stimulates vitellogenesis, and the seminal protein sex peptide (SP) has long been implicated as a mating signal that stimulates JH biosynthesis. In this review, we discuss our new findings that explain how the nervous system gates JH biosynthesis and vitellogenesis associated with reproductive maturation and the SP-induced post-mating response. Mated females exhibit diurnal rhythmicity in oogenesis. A subset of brain circadian pacemaker neurons produce Allatostatin C (AstC) to generate a circadian oogenesis rhythm by indirectly regulating JH and vitellogenesis through the brain insulin-producing cells. We also discuss genetic evidence that supports this model and future research directions.

• Journal of Nutrition and Health
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• v.56 no.2
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• pp.140-154
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• 2023

Purpose: Deodeok (Codonopsis lanceolata) is generally used in conventional medicines and is considered to have remedial properties to cure several diseases. However, application of the C. lanceolata bud as a novel food ingredient has not been fully explored. Hydrogen peroxide (H₂O₂) is associated with the production of oxidative damage that results in mutagenesis, carcinogenesis, and cell death. This study examines the neuroprotective effect of C. lanceolate bud extracts (CLBE) on H₂O₂-stimulated apoptosis in SH-SY5Y cells. Methods: C. lanceolata bud of length 10 to 15 cm was collected and extracted using 70% ethanol. Cytotoxicity was evaluated by the EZ-cytox reagent, measurement of lactic dehydrogenase (LDH) release and reactive oxygen species (ROS). The morphological changes of the nuclei were determined using the Hoechst 33258 dye. Enzyme activities were analyzed using the caspase activity assay kit. Related protein expressions were quantified by the Western blot immunoassay in H₂O₂-stimulated SH-SY5Y cells. Results: Cell viability, LDH release and ROS generation, demonstrated neuroprotective effects of CLBE in H₂O₂-stimulated SH-SY5Y cells. The occurrence of apoptosis in H₂O₂-stimulated cells was confirmed by caspase activity, which was increased in H₂O₂-stimulated SH-SY5Y cells compared to the unexposed group. Pretreatment of CLBE was observed to inhibit the H₂O₂-stimulated apoptosis. In addition, exposure to CLBE resulted in increased expression of the Bcl-2 (B cell lymphoma 2) protein and decreased expression of the Bax (Bcl2 associated X) protein. Conclusion: This study shows that exposure to CLBE alleviates the H₂O₂-stimulated neuronal damage in SH-SY5Y cells. Our results indicate the potential application of CLBE in neurodegenerative disease therapy or prevention.