• The Korea Journal of Herbology
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• v.28 no.6
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• pp.79-86
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• 2013

Objectives : The purpose of this study is to investigate neuroprotective effects and molecular mechanisms of luteolin against ${\beta}$-amyloid ($A{\beta}_{25-35}$)-induced oxidative cell death in BV-2 cells. Methods : The protective effects of luteolin against $A{\beta}_{25-35}$-induced cytotoxicity and apoptotic cell death were determined by MTT dye reduction assay and TUNEL staining, respectively. The apoptotic cell death was further analyzed by measuring mitochondrial transmembrane potential and expression of pro- and/or anti-apoptotic proteins. To elucidate the molecular mechanisms underlying the protective effects of luteolin, intracellular accumulation of reactive oxygen species, oxidative damages, and expression of antioxidant enzymes were examined. Results : Luteolin pretreatment effectively attenuated $A{\beta}_{25-35}$-induced apoptotic cell death indices such as DNA fragmentation, dissipation of mitochondrial transmembrane potential, increased Bax/Bcl-2 ratio, and activation of c-Jun N-terminal kinase and caspase-3 in BV-2 cells. Furthermore, $A{\beta}_{25-35}$-induced intracellular formation of reactive oxygen species and subsequent oxidative damages such as lipid peroxidation and depletion of endogenous antioxidant glutathione were suppressed by luteolin treatment. The neuroprotective effects of luteolin might be mediated by up-regulation of cellular antioxidant defense system via up-regulation of ${\gamma}$-glutamylcysteine ligase, a rate-limiting enzyme in the glutathione biosynthesis and superoxide dismutase, an enzyme involved in dismutation of superoxide anion into oxygen and hydrogen peroxide. Conclusions : These findings suggest that luteolin has a potential to protect against $A{\beta}_{25-35}$-induced neuronal cell death and damages thereby exhibiting therapeutic utilization for the prevention and/or treatment of Alzheimer's disease.

• Journal of Ginseng Research
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• v.48 no.1
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• pp.1-11
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• 2024

Fresh ginseng is prone to spoilage due to its high moisture content. For long-term storage, most fresh ginsengs are dried to white ginseng (WG) or steamed for hours at high temperature/pressure and dried to form Korean Red ginseng (KRG). They are further processed for ginseng products when subjected to hot water extraction/concentration under pressure. These WG or KRG preparation processes affect ginsenoside compositions and also other ginseng components, probably during treatments like steaming and drying, to form diverse bioactive phospholipids. It is known that ginseng contains high amounts of gintonin lysophosphatidic acids (LPAs). LPAs are simple lipid-derived growth factors in animals and humans and act as exogenous ligands of six GTP-binding-protein coupled LPA receptor subtypes. LPAs play diverse roles ranging from brain development to hair growth in animals and humans. LPA-mediated signaling pathways involve various GTP-binding proteins to regulate downstream pathways like [Ca²⁺]_i transient induction. Recent studies have shown that gintonin exhibits anti-Alzheimer's disease and antiarthritis effects in vitro and in vivo mediated by gintonin LPAs, the active ingredients of gintonin, a ginseng-derived neurotrophin. However, little is known about how gintonin LPAs are formed in high amounts in ginseng compared to other herbs. This review introduces atypical or non-enzymatic pathways under the conversion of ginseng phospholipids into gintonin LPAs during steaming and extraction/concentration processes, which exert beneficial effects against degenerative diseases, including Alzheimer's disease and arthritis in animals and humans via LPA receptors.

• Journal of Marine Bioscience and Biotechnology
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• v.10 no.1
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• pp.1-8
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• 2018

The objective of this study was to purify and characterize the ${\beta}-secretase$ inhibitor from enzymatic hydrolysates of blackfin flounder muscle, for development of a novel anti-dementia agent that may be used in the drug or functional food industries. ${\beta}-secretase$ inhibitory peptide was purified from various enzymatic hydrolysates of blackfin flounder muscle. Among six enzymatic hydrolysates, the Alcalase hydrolysate revealed highest ${\beta}-secretase$ inhibitory activity. Consecutive purification of the blackfin flounder muscle hydrolysate using Sephadex G-25 column chromatography and octadecylsilane C18 reversed phase HPLC techniques were used to isolate a potent ${\beta}-secretase$ inhibitory peptide composed of 5 amino acids, Leu-Thr-Gln-Asp-Trp (MW: 526.7 Da). The $IC_{50}$ value of purified ${\beta}-secretase$ inhibitory peptide was $126.93{\mu}M$. Results of this study suggest that peptides derived from blackfin flounder muscle may be beneficial as anti-dementia compounds in functional foods or as pharmaceuticals.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.4
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• pp.307-319
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• 2021

Dysregulation of the Wnt pathway causes various diseases including cancer, Parkinson's disease, Alzheimer's disease, schizophrenia, osteoporosis, obesity and chronic kidney diseases. The modulation of dysregulated Wnt pathway is absolutely necessary. In the present study, we evaluated the anti-inflammatory effect and the mechanism of action of Wnt-C59, a Wnt signaling inhibitor, in lipopolysaccharide (LPS)-stimulated epithelial cells and macrophage cells. Wnt-C59 showed a dose-dependent anti-inflammatory effect by suppressing the expression of proinflammatory cytokines including IL6, CCL2, IL1A, IL1B, and TNF in LPS-stimulated cells. The dysregulation of the Wnt/β-catenin pathway in LPS stimulated cells was suppressed by WntC59 treatment. The level of β-catenin, the executor protein of Wnt/β-catenin pathway, was elevated by LPS and suppressed by Wnt-C59. Overexpression of β-catenin rescued the suppressive effect of Wnt-C59 on proinflammatory cytokine expression and nuclear factor-kappa B (NF-κB) activity. We found that the interaction between β-catenin and NF-κB, measured by co-immunoprecipitation assay, was elevated by LPS and suppressed by Wnt-C59 treatment. Both NF-κB activity for its target DNA binding and the reporter activity of NF-κB-responsive promoter showed identical patterns with the interaction between β-catenin and NF-κB. Altogether, our findings suggest that the anti-inflammatory effect of Wnt-C59 is mediated by the reduction of the cellular level of β-catenin and the interaction between β-catenin and NF-κB, which results in the suppressions of the NF-κB activity and proinflammatory cytokine expression.

• Food Science and Biotechnology
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• v.15 no.2
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• pp.244-247
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• 2006

Neuronal cell death significantly contributes to neuronal loss in neurological injury and disease. Typically, neuronal loss or destruction upon exposure to neurotoxins, oxidative stress, or DNA damage causes neurodegenerative diseases such as Alzheimer's disease. In this study, we attempted to determine whether ginsenoside Rg3 from red ginseng has a neuroprotective effect via an anti-apoptotic role induced by S-nitroso-N-acetylpenicillamine (SNAP) at the molecular level. We also investigated the antioxidant effect of Rg3 using a metal-catalyzed reaction with $Cu^{2+}/H_2O_2$. Our results showed that Rg3 ($40-100\;{\mu}g/mL$) protected SK-N-MC neuroblastoma cells under cytotoxic conditions and effectively protected DNA from fragmentation. In the signal pathway, caspase-3, and poly (ADP-ribose) polymerase (PARP) were kept at an inactivated status when pretreated with Rg3 in all ranges. In particular, the important upstream p-Akt signal pathway was increased in a dose-dependent manner, which indicates that Rg3 may contribute to cell survival. We also found that oxidative stress can be mitigated by Rg3. Therefore, we have concluded that Rg3 plays a certain role in neurodegenerative pathogenesis via an anti apoptotic, antioxidative effect.

• Korean Journal of Pharmacognosy
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• v.51 no.3
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• pp.151-157
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• 2020

When blood vessels are damaged, a rapid hemostatic reaction occurs to minimize blood loss and maintain normal circulation. Platelet activation and aggregation is essential in this process. However, excessive platelet aggregation or abnormal platelet aggregation may be the cause of cardiovascular disease, such as thrombosis, stroke and atherosclerosis. Therefore, it is important to prevent and treat cardiovascular disease by finding substances that can regulate platelet activation and suppress aggregation reactions. Isoscopoletin, which is mainly found in the roots of plants Artemisia or Scopolia, has been reported to have potential pharmacological effects on anticancer and Alzheimer's disease, but its role and mechanisms for platelet aggregation and thrombus formation are unknown. This study confirmed the effect of isoscopoletin on major regulation of collageninduced human platelet aggregation, TXA₂ production and intracellular granular secretion (ATP and serotonin release). In addition, the effects of isoscopoletin on phosphorylation of phosphorylated proteins PI3K/Akt and MAPK involved in signal transduction in platelet aggregation was studied. As a result, isoscopoletin significantly inhibited the phosphorylation of PI3K/Akt and MAPK, significantly inhibiting platelet aggregation through TXA₂ production and intracellular granular secretion (ATP and serotonin release). Therefore, we suggest that isoscopoletin is an anti-platelet substance that regulates phosphorylation of phosphorus proteins such as PI3K/Akt and MAPK and is valuable as a preventive and therapeutic agent for platelet-derived cardiovascular disease.

• Journal of Life Science
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• v.28 no.8
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• pp.931-937
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• 2018

Triptolide is a compound found in Tripterygium wilfordii and reported to have an anti-inflammatory and anti-oxidant activities. A previous study shows that the dietary supplementation with triptolide increases resistance to environmental stressors, including oxidative stress, heat shock, and ultraviolet irradiation, and extends lifespan in C. elegans. Here, we investigated the underlying mechanisms involved in the lifespan-extending effect of triptolide. The effect of triptolide on age-related diseases, such as diabetes mellitus and Alzheimer's disease, was also examined using animal disease models. The longevity phenotype conferred by triptolide was not observed in the eat-2 mutant, a well-known genetic model of dietary restriction, while there was an additional lifespan extension with triptolide in age-1 and clk-1 mutants. The long lifespan of age-1 mutant is resulted from a reduced insulin/IGF-1-like signaling and the clk-1 mutant lives longer than wild-type due to dysfunction of mitochondrial electron transport chain reaction. The effect of dietary restriction using bacterial dilution on lifespan also overlapped with that of triptolide. The toxicity of high glucose diet or transgenic human amyloid beta gene was significantly suppressed by the supplementation with triptolide. These findings suggest that triptolide can mimic the effect of dietary restriction on lifespan and onset of age-related diseases. We conclude that triptolide can be a strong candidate for the development of dietary restriction mimetics.

• Journal of Microbiology and Biotechnology
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• v.34 no.3
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• pp.487-494
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• 2024

Recently, the term metabiotics has emerged as a new concept of probiotics. This concept entails combining existing probiotic components with metabolic by-products improve specific physiological functionalities. Representative ingredients of these metabiotics include short-chain fatty acids (SCFAs), bacteriocins, polysaccharides, and peptides. The new concept is highly regarded as it complements the side effects of existing probiotics and is safe and easy to administer. Known health functions of metabiotics are mainly immune regulation, anti-inflammatory, anticancer, and brain-neurological health. Research has been actively conducted on the health benefits related to the composition of intestinal microorganisms. Among them, the focus has been on brain neurological health, which requires extensive research. This study showed that neurological disorders, such as depression, anxiety, autism spectrum disorder, Alzheimer's disease, and Parkinson's disease, can be treated and prevented according to the gut-brain axis theory by changing the intestinal microflora. In addition, various studies are being conducted on the immunomodulatory and anticancer effects of substances related to metabiotics of the microbiome. In particular, its efficacy is expected to be confirmed through human studies on various cancers. Therefore, developing various health functional effects of the next-generation probiotics such as metabiotics to prevent or treatment of various diseases is anticipated.

• The Journal of Korean Medicine
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• v.29 no.1
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• pp.106-116
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• 2008

Objectives : Peroxynitrite $(ONOO^-)$, superoxide anion radical $({\cdot}O_2^-)$ and nitric oxide (NO) are cytotoxic because they can oxidize several cellular components such as proteins, lipids and DNA. They have been implicated in the aging processes, and age-related diseases such as Alzheimer's disease, rheumatoid arthritis, cancer and atherosclerosis. The aim of this study was to investigate the $ONOO^-$, NO, and $({\cdot}O_2^-)$ scavenging and anti-inflammatory activities of Mori Fructus in ob/ob mice. Methods : Mice were grouped and treated for 5 weeks as follows. Both the normal lean (C57/BL6J black mice) and control obese (ob/ob mice) groups received the standard chow. The experimental groups were fed a diet of chow supplemented with 7.5, 15 and 30 mg Mori Fructus per 1 kg of body weight for 14 days. For this study, the fluorescent probes, namely 2',7'-dichlorodihydrofluorescein diacetate (DCFDA), 4,5-diaminofluorescein (DAF-2) and dihydrorhodamine 123 (DHR 123) were used. Western blotting was performed using anti-phospho $I{\kappa}B-\alpha$, anti-IKK-$\alpha$, anti-NF-${\kappa}B$ (p50, p65), anti-COX-2 and anti-iNOS respectively. Results : Mori Fructus inhibited the generation of $ONOO^-$, NO and $({\cdot}O_2^-)$ in the lipopolysaccharide (LPS)-treated mouse kidney postmitochondria in vitro. The generation of $ONOO^-$, NO and $({\cdot}O2^-)$ were inhibited in the Mori Fructus-administered ob/ob mice groups. The GSH/GSSG ratio decreased in the ob/ob mice, whereas they improved in the Mori Fructus-administered groups. Mori Fructus inhibited the expression of phospho $I{\kappa}B-\alpha$, IKK-$\alpha$, COX-2, iNOS genes, and thereby the activation of NF-$I{\kappa}B$. Conclusions : These results suggest that Mori Fructus is an effective $ONOO^-$, $({\cdot}O_2^-)$ and NO scavenger, and therefore it might be a potential therapeutic drug against the inflammation process and inflammation-related diseases.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.6
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• pp.1810-1820
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• 2004

The purpose of this study was to estimate the effects of Ramulus et Uncus Uncariae DM fraction on CT105-injuried neuronal cells. We were examined by ROS formation, neurite outgrowth assay and DPPH scravage assay. Additionally, we investigated the association between the CT105 and neurite degeneration caused by CT105-induced apoptotic response in neurone cells. We studied on the regeneratory and inhibitory effects of anti-Alzheimer disease in pCT105-induced neuroblastoma cell lines by REUD. Findings from our experiments have shown that REUD inhibits the synthesis or activities of CT105, which has neurotoxityies and apoptotic activities in cell line. In addition, treatment of REUD(>50㎍/㎖ for 12 hours) partially prevented CT105-induced cytotoxicity in SK-N-SH cell lines, and were inhibited by the treatment with its. REUD(>50㎍/㎖ for 12 hours) repaired CT105-induced neurite outgrowth when SK-N-SH cell lines was transfected with CT105. As the result of this study, In REUD group, the apoptosis in the nervous system was inhibited, the repai: against the degeneration of Neuroblastoma cells by CT105 expression was promoted. Base on these findings, REUD may be beneficial for the treatment of AD.