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7,8,4'-Trihydroxyisoflavone, a Metabolized Product of Daidzein, Attenuates 6-Hydroxydopamine-Induced Neurotoxicity in SH-SY5Y Cells

  • Ko, Yong-Hyun;Kim, Seon-Kyung;Kwon, Seung-Hwan;Seo, Jee-Yeon;Lee, Bo-Ram;Kim, Young-Jung;Hur, Kwang-Hyun;Kim, Sun Yeou;Lee, Seok-Yong;Jang, Choon-Gon
    • Biomolecules & Therapeutics
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    • v.27 no.4
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    • pp.363-372
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    • 2019
  • Daidzein isolated from soybean (Glycine max) has been widely studied for its antioxidant and anti-inflammatory activities. However, the protective effects of 7,8,4'-trihydroxyisoflavone (THIF), a major metabolite of daidzein, on 6-hydroxydopamine (OHDA)-induced neurotoxicity are not well understood. In the current study, 7,8,4'-THIF significantly inhibited neuronal cell death and lactate dehydrogenase (LDH) release induced by 6-OHDA in SH-SY5Y cells, which were used as an in vitro model of Parkinson's disease (PD). Moreover, pretreatment with 7,8,4'-THIF significantly increased the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) and decreased malondialdehyde (MDA) activity in 6-OHDA-induced SH-SY5Y cells. In addition, 7,8,4'-THIF significantly recovered 6-OHDA-induced cleaved caspase-3, cleaved caspase-9, cleaved poly-ADP-ribose polymerase (PARP), increased Bax, and decreased Bcl-2 levels. Additionally, 7,8,4'-THIF significantly restored the expression levels of phosphorylated c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase 1/2 (ERK 1/2), phosphatidylinositol 3-kinases (PI3K)/Akt, and glycogen synthase kinase-3 beta ($GSK-3{\beta}$) in 6-OHDA-induced SH-SY5Y cells. Further, 7,8,4'-THIF significantly increased the reduced tyrosine hydroxylase (TH) level induced by 6-OHDA in SH-SY5Y cells. Collectively, these results suggest that 7,8,4'-THIF protects against 6-OHDA-induced neuronal cell death in cellular PD models. Also, these effects are mediated partly by inhibiting activation of the MAPK and PI3K/Akt/$GSK-3{\beta}$ pathways.

Supplementation with psyllium seed husk reduces myocardial damage in a rat model of ischemia/reperfusion

  • Lim, Sun Ha;Lee, Jongwon
    • Nutrition Research and Practice
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    • v.13 no.3
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    • pp.205-213
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    • 2019
  • BACKGROUND/OBJECTIVES: Myocardial infarction (MI) is caused by extensive myocardial damage attributed to the occlusion of coronary arteries. Our previous study in a rat model of ischemia/reperfusion (I/R) demonstrated that administration of arabinoxylan (AX), comprising arabinose and xylose, protects against myocardial injury. In this study, we undertook to investigate whether psyllium seed husk (PSH), a safe dietary fiber containing a high level of AX (> 50%), also imparts protection against myocardial injury in the same rat model. MATERIALS/METHODS: Rats were fed diets supplemented with PSH (1, 10, or 100 mg/kg/d) for 3 d. The rats were then subjected to 30 min ischemia through ligation of the left anterior descending coronary artery, followed by 3 h reperfusion through release of the ligation. The hearts were harvested and cut into four slices. To assess infarct size (IS), an index representing heart damage, the slices were stained with 2,3,5-triphenyltetrazolium chloride (TTC). To elucidate underlying mechanisms, Western blotting was performed for the slices. RESULTS: Supplementation with 10 or 100 mg/kg/d of PSH significantly reduces the IS. PSH supplementation (100 mg/kg/d) tends to reduce caspase-3 generation and increase BCL-2/BAX ratio. PSH supplementation also upregulates the expression of nuclear factor erythroid 2-related factor 2 (NRF2), and its target genes including antioxidant enzymes such as glutathione S-transferase mu 2 (GSTM2) and superoxide dismutase 2 (SOD2). PSH supplementation upregulates some sirtuins ($NAD^+$-dependent deacetylases) including SIRT5 (a mitochondrial sirtuin) and SIRT6 and SIRT7 (nuclear sirtuins). Finally, PSH supplementation upregulates the expression of protein kinase A (PKA), and increases phosphorylated cAMP response element-binding protein (CREB) (pCREB), a target protein of PKA. CONCLUSIONS: The results from this study indicate that PSH consumption reduces myocardial I/R injury in rats by inhibiting the apoptotic cascades through modulation of gene expression of several genes located upstream of apoptosis. Therefore, we believe that PSH can be developed as a functional food that would be beneficial in the prevention of MI.

The Treatment Effect of Ulcerative Colitis of Supercritical Heat-Treated Radish Extracts

  • Kim, Hyun-Kyoung
    • International Journal of Internet, Broadcasting and Communication
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    • v.13 no.2
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    • pp.145-155
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    • 2021
  • With the recent rapid improvement in the standards of life and westernization of dietary lifestyles, the consumption of high-calorie diets such as high-fat and high-protein red meat and instant foods has increased, while less vegetables containing dietary fiber are consumed. In addition to that, stress, erroneous dietary behaviors, and contaminated environments are linked to the risk of developing ulcerative colitis, which is on the rise. Another cause of ulcerative colitis is that involve laxative abuse, including repeated, frequent use of laxatives, and include such conditions as deteriorated bowel function, irritable bowel syndrome, diarrhea, intestinal inflammation, etc. The present study aimed to investigate the comparative evaluation of pharmacological efficacy between sulfasalazine alone and combination with herbal medicine on dextran sodium sulfate (DSS)-induced UC in mice. Balb/c mice received 5% DSS in drinking water for 7 days to induce colitis. Animals were divided into five groups (n = 9): group I-normal group, group II-DSS control group, group III-DSS + sulfasalazine (30 mg/kg), group IV-DSS + sulfasalazine (60 mg/kg), group V-DSS + sulfasalazine (30 mg/kg) + Radish Extract mixture (30 mg /kg) (SRE). DSS-treated mice developed symptoms similar to those of human UC, such as severe bloody diarrhea and weight loss. SRE supplementation, as well as sulfasalazine, suppressed colonic length and mucosal inflammatory infiltration. In addition, SRE treatment significantly reduced the expression of pro-inflammatory signaling molecules through suppression both mitogen-activated protein kinases (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways, and prevented the apoptosis of colon. Moreover, SRE administration significantly led to the up-regulation of antioxidant enzyme including SOD and Catalase. This is the first report that Radish extract mixture combined with sulfasalazine protects against experimental UC via the inhibition of both inflammation and apoptosis, very similar to the standard-of-care sulfasalazine.

Anti-inflammation Effect of Cyrtomium fortunei J.Sm. Extracts in Lipopolysaccharides-induced Microglia BV2 Cell (LPS로 자극한 microglia BV2 cell에서 Cyrtomium fortunei J.Sm. 추출물의 항염증 효과)

  • Jiwon Choi;Shintae Kim;Sang Yoon Choi;Inwook Choi;Jinyoung Hur
    • Journal of the Korean Society of Food Culture
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    • v.38 no.3
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    • pp.176-183
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    • 2023
  • In this study, we investigated the effect of the extracts of Cyrtomium fortunei J.Sm. (CFJ) on lipopolysaccharide (LPS) induced inflammation in mouse BV-2 microglial cells. Nitric oxide (NO) production and cell viability were measured using the Griess reagent and the (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) (MTT) assay. Inflammatory cytokines were detected by quantitative polymerase chain reaction (qPCR) in BV-2 microglial cells with and without CFJ extracts. Subsequently, mitogen-activated protein kinases (MAPKs) and antioxidant markers were assessed by western blot analysis. It was found that the CFJ extract significantly decreased the production of pro-inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α, and IL-1β) and NO in BV-2 microglial cells that were stimulated with LPS. In addition, the expression levels of the phosphorylation of the MAPK family (p38, c-Jun N-terminal kinases [JNK], and extracellular-signal regulated kinase [ERK]) were reduced by CFJ. Also, treatment with CFJ significantly increased the activities of superoxide dismutase type 1(SOD1) and Catalase in BV-2 microglial cells. Our results indicate that CFJ has a potent suppressive effect on the pro-inflammatory responses of activated BV-2 microglia. Therefore, CFJ has the potential to be an effective treatment for neurodegenerative diseases, as it can inhibit the production of inflammatory mediators in activated BV-2 microglial cells.

Neuroprotective Effects of Stachys sieboldii Miq. Extract Against Ischemia/reperfusion-induced Apoptosis in SH-SY5Y Neuroblastoma Cells (허혈-재관류 유도 신경세포사멸에 대한 초석잠 추출물의 신경보호 효과 연구)

  • Young-Kyung Lee;Chul Hwan Kim;Su Young Shin;Buyng Su Hwang;Min-Jeong Seo;Hye Jin Hwang;Kyung-Min Choi;Jin-Woo Jeong
    • 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.

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Stachys sieboldii M iq. Protects SH-SY5Y Cells Against Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury by Inhibition of Mitochondrion-Mediated Apoptosis Pathway (허혈-재관류 유도 SH-SY5Y 모델에서 미토콘드리아 매개 Apoptosis 기전 제어를 통한 초석잠 추출물의 세포보호 효과)

  • Jin-Woo Jeong;Eun Jung Ahn;Chul Hwan Kim;Su Young Shin;Seung Young Lee;Kyung-Min Choi;Chang-Min Lee
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2021.04a
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    • pp.57-57
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    • 2021
  • Oxygen glucose deprivation/re-oxygenation (OGD/R) induces neuronal injury via mechanisms that are believed to mimic the pathways associated with brain ischemia. Stachys sieboldii Miq. (Chinese artichoke), which has been extensively used in oriental traditional medicine to treat of ischemic stroke; however, the role of S. sieboldii Miq. (SSM) in OGD/R induced neuronal injury is not yet fully understood. The present research is aimed to investigate the protective effect and possible mechanisms of SSM extract treatment in an in vitro model of OGD/R to simulate ischemia/reperfusion Injury. Pretreatment of these cells with SSM significantly attenuated OGD/R-induced production of reactive oxygen species (ROS) by increasing GPx, SOD, and decreasing MDA. SSM decreased mitochondrial damage caused by OGD/R injury and inhibited the release of cyt-c from mitochondrion to cytoplasm in SH-SY5Y cells. Furthermore, neuronal cell apoptosis caused by OGD/R injury was inhibited by SSM, and SSM could decrease apoptosis by increasing ratio of Bcl-2/Bax and inhibiting caspase signaling pathway in SH-SY5Y cells. SSM demonstrated a neuroprotective effect on the simulated cerebral ischemia in vitro model, and this effect was the inhibition of mitochondria-mediated apoptosis pathway by scavenging of ROS generation. Therefore, SSM may be a promising neuroprotective strategy against ischemic stroke.

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Difference of Protoporphyrin IX Accumulation and Antioxidative Activity of Wheat and Barley by Protoporphyrinogen Oxidase-Inhibiting Herbicides (Protoporphyrinogen Oxidase 저해형 제초제에 대한 밀과 보리의 Protoporphyrin IX축적 및 항산화 방어계 차이)

  • 국용인;구자옥;천상욱
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.42 no.1
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    • pp.79-88
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    • 1997
  • This experiment was conducted to investigate the protoporphyrin Ⅸ (PPIX)accumulation, activity of antioxidative enzymes and contents of antioxidant in tolerant-wheat and susceptible-barley to protoporphyrinogen oxidase (Protox) inhibiting-herbicides [oxyfluorfen(2-chloro-l-(3-ethoxy-nitrophenoxy-4-(trifluoromethyl) benzene, acifluorfen (5-[2-chloro-4-(trifl-uoromethyl) phenoxy]-2-nitrobenzoic acid), bifenox(methyl-5-(2, 4-dichlorophenoxy) 2-nitroben-zoate), and oxadiazon (5-tert-butyl-3-(2,4-dichloro-5-isopropoxyphenyl)-1,3,4-oxadiazol-2-one)]. The tolerant-wheat and susceptible-barley were soaked in these compounds at 10$^{-6}$ M for 2hrs and exposed to light for 2,4,6 or 8hrs to investigate change of the activity of antioxidative enzymes. The activities of monodehydroascorbate reductase(MDAR), catalase(CAL) and superoxide dismutase(SOD) were lower in the barley than in the wheat after the treatement of these compounds. The activity of peroxidase(POX) was lower in the barley than in the wheat at 8hrs after the treatment of oxyfluorfen but other compounds showed no difference in activity in wheat and barley. The activity of glutathione reductase(GR) was increased in wheat and barley according as hours of treatment of these compounds became increased but its activity was no difference between wheat and barley. In the case of the content of vitamin C due to the treatment of these compounds, the wheat decreased less than the barley. After the treatment of oxyfluorfen the content of vitamin E in the wheat was higher than in the barley but other compounds didn't have any difference between wheat and barley. And after the treatment of acifluorfen the content of carotenoid was greater in the wheat than in the barley but other compounds didn't have any difference between wheat and barley. The content of glutathione (GSH, GSSG) was greater in the barley than in the wheat. The content of protoporphyrin Ⅸ (PPIX) accumulation by the treatments of these compounds was more in the barley than in the wheat. Especially, the treatment of oxyfluorfen and acifluorfen were more accumulated 2.3 and 1.3 fold in the barley than in the wheat, respectively.

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Hypoglycemic and Hypolipidemic Effects of Jerusalem artichoke Composites in Streptozotocin induced Diabetic Rats (명월초, 여주 및 울금을 포함하는 돼지감자 복합물의 streptozotocin 유발 당뇨쥐에서 혈당강하 및 체내 지질개선에 미치는 영향)

  • Hu, Wen-Si;Lee, Soo-Jung;Pyo, Jae-Ho;Kim, Sung-Hee;Sung, Nak-Ju
    • Journal of Life Science
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    • v.28 no.6
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    • pp.671-680
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    • 2018
  • Hypoglycemic and hypolipidemic effects of Jerusalem artichoke composites (JAP) with extracts of G. procumbens (12.5%), M. charantia (12.5%), and C. longa (12.5%) to H. tuberosus concentrate (JA, 50%) were evaluated in streptozotocin (STZ) induced diabetic rats. Rats were divided into seven groups: normal (Normal), diabetic control (Diabetic), group fed G. procumbens extract (0.5 g/kg bw, D-GPE), group fed JAP (0.5 g/kg bw, D-JAP1; 1.5 g/kg bw, D-JAP2), group fed JA (0.5 g/kg bw, D-JA), and group fed Metformin (0.2 g/kg bw, D-MET) as a positive control. The blood glucose levels over 4 weeks were significantly decreased in the D-JAP2 and D-MET groups compared to the other groups after 3 weeks. The serum insulin level was not significant among the groups fed an experimental diet, but the HOMA-IR value was significantly decreased compared to the diabetic control group. AST and ALT activities in the serum were lowest in D-JAP1. Total lipid and triglyceride contents in the serum decreased in the groups fed an experimental diet, and the HDL-C contents of D-GPE, D-JAP1, and D-JAP2 were significantly increased compared to the diabetic control group. Triglyceride contents in the liver tissue were significantly lower in the D-GPE, D-JAP1, and D-JAP2 groups, and hepatic TBARS content was significantly decreased in the D-JAP1 and D-JAP2 groups compared to the diabetic control group. Hepatic antioxidative enzyme levels, such as SOD, catalase, and GSH-Px, were significantly elevated in groups fed an experimental diet compared to the diabetic control group. Therefore, JAP may be more effective than JA in the human body due to its hypoglycemic and hypolipidemic activities.

Anti-oxidant and Anti-microbial Activities of Seungmakalgeuntang (복합처방인 승마갈근탕(升摩葛根湯)의 항산화 및 항균효과)

  • Lee, Jin-Young;Bae, Ho-Jung;Park, Tae-Soon;Kim, Tae-Wan;Moon, Doo-Hwan;Kwon, O-Jun;Son, Jun-Ho;Lee, Chang-Eon;Park, Gun-Hye;Kim, Han-Hyuk;An, Bong-Jeun
    • Journal of Applied Biological Chemistry
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    • v.53 no.1
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    • pp.13-20
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    • 2010
  • Biological activities such as anti-oxidative and anti-microbial of the Seungmakalgeuntang, a traditional prescription, were evaluated. The electron donating ability of water, ethanol, supercritical fluid and 1,3-butylene glycol extract of Seungmakalgeuntang showed more than 50% at a 100 ppm concentration. At a 1000 ppm concentration, the superoxide dismutase-like activities of ethanol and supercritical fluid extract of Seungmakalgeuntang showed less than 50%. xanthine oxidase inhibition effect of the supercritical fluid extract showed more than 70% at a 1,000 ppm concentration, which was higher than vitamin C. From the measurement on lipid oxidation, the $Fe^{2+}$ chelating abilities of the supercritical fluid extract of Seungmakalgeuntang was more than 60% at a 100 ppm concentration. Also the $Cu^{2+}$ chelating abilities of supercritical fluid extract Seungmkalgeuntang was showed more than 60% at a 500 ppm concentration. Clear zones formed by sample against the human skin-resident microflora such as Staphylococcus epidermidis, Staphylococcus aureus and Propionibacterium acne of ethanol and supercritical fluid extract of Seungmakalgeuntang showed the highest among all the extracts tested using a 4mg/disc. The minimum inhibitory concentration (MIC) against both S. epidermidis and S. aureus showed 2,500 ppm in the extract of the supercritical fluid.

Memory improvement effect of Artemisia argyi H. fermented with Monascus purpureus on streptozotocin-induced diabetic mice (스트렙토조토신으로 유도된 당뇨 마우스에서 Monascus purpureus을 이용한 발효 쑥의 기억력 개선 효과)

  • Lee, Chang Jun;Lee, Du Sang;Kang, Jin Yong;Kim, Jong Min;Park, Seon Kyeong;Kang, Jeong Eun;Kwon, Bong Seok;Park, Sang Hyun;Park, Su Bin;Ha, Gi-Jeong;Heo, Ho Jin
    • Korean Journal of Food Science and Technology
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    • v.49 no.5
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    • pp.550-558
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    • 2017
  • The effect of Artemisia argyi H. under liquid-state fermentation by Monascus purpureus (AAFM) on cognitive impairments has been studied in a mice model of diabetes-associated cognitive decline induced by streptozotocin (STZ). C57BL/6 mice (9 weeks of age, male) were separated into four groups: a normal control, STZ-induced diabetic mouse group (STZ group), Artemisia argyi H. (AA) 10 group (diabetic mouse+AA 10 mg/kg/day), AAFM 10 group (diabetic mouse+AAFM 10 mg/kg/day). Administration of AA and AAFM significantly improved glucose tolerance, as shown by the intraperitoneal glucose tolerance test (IPGTT), and ameliorated cognitive deficit, as shown by the behavioral tests including passive avoidance, Morris water maze, and Y-maze tests. After behavioral tests, the cholinergic system was examined by assessment of the acetylcholine (ACh) level and acetylcholinesterase (AChE) inhibitory activity, and the antioxidant system was also assessed by measuring malondialdehyde (MDA) and superoxide dismutase (SOD) levels in the brain and liver.