• Journal of Ginseng Research
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• v.47 no.3
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• pp.448-457
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• 2023

Background: Alzheimer's disease (AD) is a common form of dementia, and impaired mitophagy is a hallmark of AD. Mitophagy is mitochondrial-specific autophagy. Ginsenosides from Ginseng involve in autophagy in cancer. Ginsenoside Rg1 (Rg1 hereafter), a single compound of Ginseng, has neuroprotective effects on AD. However, few studies have reported whether Rg1 can ameliorate AD pathology by regulating mitophagy. Methods: Human SH-SY5Y cell and a 5XFAD mouse model were used to investigate the effects of Rg1. Rg1 (1µM) was added to β-amyloid oligomer (AβO)-induced or APPswe-overexpressed cell models for 24 hours. 5XFAD mouse models were intraperitoneally injected with Rg1 (10 mg/kg/d) for 30 days. Expression levels of mitophagy-related markers were analyzed by western blot and immunofluorescent staining. Cognitive function was assessed by Morris water maze. Mitophagic events were observed using transmission electron microscopy, western blot, and immunofluorescent staining from mouse hippocampus. The activation of the PINK1/Parkin pathway was examined using an immunoprecipitation assay. Results: Rg1 could restore mitophagy and ameliorate memory deficits in the AD cellular and/or mouse model through the PINK1-Parkin pathway. Moreover, Rg1 might induce microglial phagocytosis to reduce β-amyloid (Aβ) deposits in the hippocampus of AD mice. Conclusion: Our studies demonstrate the neuroprotective mechanism of ginsenoside Rg1 in AD models. Rg1 induces PINK-Parkin mediated mitophagy and ameliorates memory deficits in 5XFAD mouse models.

• Journal of Nutrition and Health
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• v.48 no.5
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• pp.451-456
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• 2015

Purpose: Neuronal apoptotic events induced by aging and hypoxic/ischemic conditions is an important risk factor in neurodegenerative diseases such as ischemia stroke and Alzheimer's disease. The peel of Citrus sunki Hort. ex Tanaka has long been used as a traditional medicine, based on multiple biological activities including anti-oxidant, anti-inflammation, and anti-obesity. In the current study, we examined the actions of fermented C. sunki peel extract against cobalt chloride ($CoCl_2$)-mediated hypoxic death in human neuroblastoma SH-SY5Y cells. Methods: Cell viability was measured by trypan blue exclusion. Expression of apoptosis related proteins and release of cytochrome c were detected by western blot. Production of intracellular reactive oxygen species (ROS) and apoptotic morphology were examined using 2',7'-dichlorofluorescin diacetate (DCF-DA) and 4',6-diamidino-2-phenylindole (DAPI) staining. Results: Exposure to $CoCl_2$, a well-known mimetic agent of hypoxic/ischemic condition, resulted in neuronal cell death via caspase-3 dependent pathway. Extract of fermented C. sunki peel significantly rescued the $CoCl_2$-induced neuronal toxicity with the cell viability and appearance of apoptotic morphology. Cytoprotection with fermented C. sunki peel extract was associated with a decrease in activities of caspase-3 and cleavage of poly (ADP ribose) polymerase (PARP). In addition, increase in the intracellular ROS and release of cytochrome c from mitochondria to the cytosol were inhibited by treatment with extract of fermented C. sunki peel. Conclusion: Based on these data, fermented C. sunki peel extract might have a protective effect against $CoCl_2$-induced neuronal injury partly through generation of ROS and effectors involved in mitochondrial mediated apoptosis.

• Korean Journal of Materials Research
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• v.20 no.3
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• pp.132-136
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• 2010

This study examined the biostability and drug delivery efficiency of g-$Fe_2O_3$ magnetic nanoparticles (GMNs) by cytotoxicity tests using various tumor cell lines and normal cell lines. The GMNs, approximately 20 nm in diameter, were prepared using a chemical coprecipitation technique, and coated with two surfactants to obtain a water-based product. The particle size of the GMNs loaded on hangamdan drugs (HGMNs) measured 20-50 nm in diameter. The characteristics of the particles were examined by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-TEM) and Raman spectrometer. The Raman spectrum of the GMNs showed three broad bands at 274, 612 and $771\;cm^1$. A 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay showed that the GMNs were non-toxic against human brain cancer cells (SH-SY5Y, T98), human cervical cancer cells (Hela, Siha), human liver cancer cells (HepG2), breast cancer cells (MCF-7), colon cancer cells (CaCO2), human neural stem cells (F3), adult mencenchymal stem cells (B10), human kidney stem cells (HEK293 cell), human prostate cancer (Du 145, PC3) and normal human fibroblasts (HS 68) tested. However, HGMNs were cytotoxic at 69.99% against the DU145 prostate cancer cell, and at 34.37% in the Hela cell. These results indicate that the GMNs were biostable and the HGMNs served as effective drug delivery vehicles.

• Korean Journal of Acupuncture
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• v.39 no.2
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• pp.34-42
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• 2022

Objectives : Parkinson's disease (PD) is a neurodegenerative disease caused by dopaminergic neuronal death in the substantia nigra pars compacta. PD is known to be linked with mitochondrial dysfunction and increased oxidative stress. In this study, anti-cytotoxic and anti-oxidative effect of 12 herbal formulae were compared. Methods : According to experts' advice, 12 types of herbal formulae (Gamisoyosan, Galgeuntang, Galgeunhaegitang, Banhabaekchoolcheonmatang, Bojungikgitang, Boheotang, Sihogyejitang, Sihosogantang, Sihocheonggantang, Ojeoksan, Cheongsanggyeontongtang and Palmultang) were selected from 56 types of herbal formulae covered by the National Health Insurance Service in Korea. To detect anti-oxidative effect, 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was performed, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to detect anti-cytotoxic effect of 12 herbal formulae using SH-SY5Y human neuroblastoma cells. Results : In DPPH assay, anti-oxidant activity was increased in a dose-dependent manner and half maximal inhibitory concentration was highest in the order of Galgeuntang, Gamisoyosan, Galgeunhaegitang, Ojeoksan, Palmultang, Sihogyejitang, Sihosogantang, Cheongsanggyeontongtang, Sihocheonggantang, Bojungikgitang, Boheotang and Banhabaekchoolcheonmatang. In MTT assay, concentration of 80% cell survival was highest in the order of Sihosogantang, Cheongsanggyeontongtang, Sihocheonggantang, Sihogyejitang, Bojungikgitang, Galgeuntang, Ojeoksan, Boheotang, Palmultang, Galgeunhaegitang, Banhabaekchoolcheonmatang and Gamisoyosan. Formulae with more than 50% DPPH radical scavenging activity at concentrations for 80% cell survival were Sihosogantang, Cheongsanggyeontongtang, Sihogyejitang, Galgeuntang and Sihocheonggantang. Conclusions : Sihosogantang, Cheongsanggyeontongtang, Sihogyejitang, Galgeuntang and Sihocheonggantang extracts can be candidate medicines for PD, but the effect should be validated in PD models.

• The Korea Journal of Herbology
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• v.24 no.2
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• pp.87-92
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• 2009

Objectives : This study was performed to evaluate the neuroprotective effect of water extracts from Nelumbinis semen (NSW) in dopaminergic cells. Methods : We performed 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay, 2,2-azinobis3-ethyl-benzothiazoline-6-sulfonic acid (ABTS) cation scavenging assay, and determination of total polyphenolic content to examine the antioxidant effects of NSW. We also evaluated the neuroprotective effects against 6-hydroxydopamine (6-OHDA)-induced toxicity using 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl-tetrazolium bromide assay (MIT) assay, trypan blue cytotoxicity assay, and nitric oxide assay in SH-SY5Y cells and tyrosine hydroxylase (TH) immunohistochemistry in primary rat dopaminergic neurons. Results : NSW showed $IC_{50}$ values of 184.80 and 92.90 ${\mu}$g/mL in DPPH and in ABTS assays, respectively. NSW showed 1.05% of total polyphenol contents. NSW showed protective effect against 6-0HDA-induced neurotoxicity whereas no influence on cell viability at the concentration of 1${\sim}$50 ${\mu}$g/mL. NSW reduced NO generation while 6-OHDA produced it. Moreover, it protected rat dopaminergic neurons against 6-0HDA at a dose of 1 ${\mu}$g/mL. Conclusions : These results indicated that NSW has neuroprotective effect against 6-0HDA-induced neurotoxicity through antioxidant activity in dopaminergic cell culture.

• Journal of the Korean Society of Food Science and Nutrition
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• v.30 no.4
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• pp.657-661
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• 2001

Osteoporosis that is associated with ovarian hormone deficiency following menopause (postmenopausal osteoporosis) is by far the most common cause of age-related bone loss. Isoflavone has been reported as a natural substance that possibly minimizes bone loss in postmenopausal women. This study was conducted to investigate the preventing, treating effects of isoflavone on bone loss in ovariectomized rats. 120 Sprague Dawley rats of 13 week-old were devided into 2 groups, a treatment group and prevention group. Each group was consisted of six subgroups; control (CON), sham operated (SH) or ovariectomized (OVX) and isoflavone supplemented goups: OVX+0.25mg isoflavone/kg diet (OL), OVX+0.8mg isoflavone/kg diet(OM) and OVX+2.5mg isoflavone/kg diet(OH). to study the preventing effects of isoflavone on bone loss, OL, OM and OH groups were fed with isoflavone from 4 days after ovariectomization. Treating effects of isoflavone on bone metabolism were investigated with OL, OM, OH groups supplemented with isoflavone from 8 weeks after ovariectomization. Isoflavone supplementation continued for 8 weeks. At 8 weeks after ovariectomization significant increase in alkaline phosphatase occurred comparing with CON and SH group. By isoflavone supplementation from 4 days after ovariectomy alkaline phosphatase and urinary hydroxyproline were lowered and bone mineral density, bone strength of the femur and tibia and bone dry weight were slightly enhanced with no significant difference. Isoflavone supplemented group at the level of 0.8mg/kg diet (OM group) had significantly lower serum alkaline phosphatase, urinary hydroxyproline, and higher strength of femur than OVX group. Groups with isoflavone supplementation fro 8 weeks after ovariectomy had lower level of serum alkaline phosphatase, urinary hydroxyproline than OVX group. Bone mineral density, bone dry weight and bone strength of the femur and tibia were slightly enhanced by isoflavone supplementation. However there was no significanct difference between OVS ad isoflavone supplementation groups. The results suggest that isoflavone might have potential role for preventing postmenopausal bone loss. Isoflavone supplementation at early stage of postemenopause may be beneficial to age-related bone health.

• Korean Journal of Pharmacognosy
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• v.39 no.4
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• pp.290-294
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• 2008

The objective of this study is screening the anti-oxidative effects of several plant MeOH extracts against oxidative stress in Neuroblastoma cell. Oxidative stress has been implicated in the pathogenesis of many neurotoxicity, neurodegenerative disorders and cell death. This oxidative stress is generated by ROS (Reactive Oxygen Species) such as nitric oxide, nitrogen dioxide, peroxyl, superoxide ($O_2^-$), hydroxyl, alkoxyl. So, in the present study, we induced oxidative stress by treatment of sodium nitroprusside (2.5 mM) in human neuroblastoma SH-SY5Y cell which was treated samples before 24hr, and cell viability was measured by MTT reduction assay. Of those tested, the extracts of Paeonia japonica (roots), Eucommia ulmoides (炒)(barks), Paeonia japonica (曝乾)(roots), Phyllostachys bambusoides (stems), Polygala tenuifolia (去心, 炒)(roots), Paeonia japonica (roots), Polygala tenuifolia (roots), Machilus thunbergii (barks), Mallotus japonicus (leaves), Poria cocos (whole), Sophora flavescens (roots), Angelica tenuissima (roots), Angelica gigas (當歸尾)(roots) showed anti-oxidative effects[$EC_{50}$<15.20 ${\mu}g$/ml(Carnosine:Positive control)]in dose dependent manner.

• Archives of Pharmacal Research
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• v.28 no.8
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• pp.923-929
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• 2005

Methanol extracts of domestic plants of Korea were evaluated as a potential inhibitor of neutral pH optimum and membrane-associated 60 kDa sphingomyelinase (N-SMase) activity. In this study, we partially purified N-SMase from bovine brain membranes using ammonium sulfate. It was purified approximately 163-fold by the sequential use of DE52, Butyl-Toyopearl, DEAE-Cellulose, and Phenyl-5PW column chromatographies. The purified N-SMase activity was assayed in the presence of the plant extracts of three hundreds species. Based on the in vitro assay, three plant extracts significantly inhibited the N-SMase activity in a time- and concentration-dependent manner. To further examine the inhibitory pattern, a Dixon plot was constructed for each of the plant extracts. The extracts of Abies nephrolepis, Acer tegmentosum, and Ginkgo biloba revealed a competitive inhibition with the inhibition constant (Ki) of $11.9 {\mu}g/mL,\;9.4{\mu}g/mL,\;and\;12.9{\mu}g/mL$, respectively. These extracts also inhibited in a dose-dependent manner the production of ceramide induced by serum deprivation in human neuroblastoma cell line SH-SY5Y.

• Journal of Korean Neurosurgical Society
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• v.64 no.5
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• pp.716-725
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• 2021

Objective : The anti-tumor effect of the beta-adrenergic receptor antagonist propranolol in breast cancer is well known; however, its activity in glioblastoma is not well-evaluated. The Notch-Hes pathway is known to regulate cell differentiation, proliferation, and apoptosis. We investigated the effect of propranolol to human glioblastoma cell lines, and the role of Notch and Hes signaling in this process. Methods : We performed immunohistochemical staining on 31 surgically resected primary human glioblastoma tissues. We also used glioblastoma cell lines of U87-MG, LN229, and neuroblastoma cell line of SH-SY5Y in this study. The effect of propranolol and isoproterenol on cell proliferation was evaluated using the MTT assay (absorbance 570 nm). The impact of propranolol on gene expression (Notch and Hes) was evaluated using real-time polymerase chain reaction (RT-PCR, whereas protein levels of Notch1 and Hes1 were measured using Western blotting (WB), simultaneously. Small interfering RNA (siRNA) was used to suppress the Notch gene to investigate its role in the proliferation of glioblastoma. Results : Propranolol and isoproterenol caused a dose-dependent decrease in cell proliferation (MTT assay). RT-PCR showed an increase in Notch1 and Hes1 expression by propranolol, whereas WB demonstrated increase in Notch1 protein, but a decrease in Hes1 by propranolol. The proliferation of U87-MG and LN229 was not significantly suppressed after transfection with Notch siRNA. Conclusion : These results demonstrated that propranolol suppressed the proliferation of glioblastoma cell lines and neuroblastoma cell line, and Hes1 was more closely involved than Notch1 was in glioblastoma proliferation.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.11
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• pp.1533-1543
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• 2016

The anti-stress effects of Punica granatum L. (family Lythraceae, PG) on $H_2O_2$/corticosterone (CORT)-induced stress in cells and sleep-deprived rats were investigated. The PG extract showed neuroprotective effects in SH-SY5Y cells against $H_2O_2$/CORT-induced stress. Sleep deprivation led to behavioral, hormonal, and biochemical alterations in the animal model. The effects of P. granatum on physiological, behavioral, and biochemical parameters aggravated by sleep deprivation were investigated. Sleep deprivation impaired physiological (survival, body weight, and drowsiness scores) and behavioral (rotarod, passive avoidance, hot hyperalgesia, and Y maze) parameters as well as biochemical factors (cortisol, serotonin, dopamine, testosterone, and growth factor I contents in serum). These parameters were significantly recovered by PG extract in a concentration-dependent manner. The PG extract also enhanced catalase, superoxide dismutase, and non-enzymatic antioxidative activities such as glutathione compared to sleep-deprived rats. On the basis of these results, our findings suggest that Punica granatum prevents impairment of body functions induced by sleep deprivation and related oxidative damage.