• Title/Summary/Keyword: Inhibitory Activity

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Synthesis and Biological Activities of Myomodulin E and its Analogs (Myomodulin E 및 유도체들의 합성 및 생리활성)

  • Go, Hye-Jin;Seo, Jung-Kil;Seo, Hae-Jeom;Lee, Min-Jeong;Park, Tae-Hyun;Kim, Gun-Do;Park, Nam-Gyu
    • Journal of Life Science
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    • v.22 no.4
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    • pp.499-507
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    • 2012
  • Previous work has characterized myomodulin A (MMA, PMSMLRLamide) and myomodulin E (MME, GLQMLRLamide) purified from the central nervous systems of the sea hare, $Aplysia$ $Kurodai$, using the anterior byssus retractor muscle (ABRM) of the mussel, $Mytilus$ $edulis$. The amino acid sequences of MMA and MME were the same as those of the myomodulin family peptide found in other mollusks. In this study, we synthesized MME, its derivatives, and other neuropeptides to investigate the relationship between the structure and biological activity of MME. The primary structures of MME's derivatives, Des[$Gly^1$]-MME, Des[$Gly^1,Leu^2$]-MME, and Des[$Gly^1,Leu^2,Gln^3$]-MME, were LQMLRLamide, QMLRLamide, and MLRLamide, respectively. MMA and synthetic peptides were tested on ABRM in $M.$ $edulis$ as well as muscle preparations in $Achatina$ $fulica$. MME displayed an inhibitory effect on phasic contraction of the ABRM at $1{\times}10^{-9}$ M or higher. MME also had a relaxing effect on the catch-tension of AMRM at $1{\times}10^{-8}$ M. Both MMA and its analogs stimulated a contractile response on the crop and relaxed the catch-relaxing response on the penial retractor muscle of $A.$ $fulica$. These results suggest that MME and its analogs have modulatory effects on various muscles of mollusks. This study has also laid the groundwork for future neural and circuit modulation studies during animal behavioral changes.

Influence of Hypoxia on Catecholamine Secretion Evoked by DMPP, McN-A-343, Excess $K^+$ and ACh from The Perfused Rat Adrenal Gland (저산소증이 흰쥐 관류부신에서 DMPP, McN-A-343, Excess $K^+$ 및 Ach의 카테콜아민 분비작용에 미치는 영향)

  • Lim Dong-Yoon;Heo Jae-Bong;Park Yoo Han
    • The Korean Journal of Pharmacology
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    • v.31 no.1 s.57
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    • pp.63-74
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    • 1995
  • It has been known that, during hypoxia, the adrenal medulla is activated to release catecholamines (CA) while hypoxia also inhibits high $K^+$ -induced CA secretion in the cultured bovine adrenal chromaffin cells. The present study was attempted to examine the effect of hypoxia on CA secretion evoked by chlinergic stimulation and membrane-depolarization from the isolated perfused rat adrenal glands and also to clarify its mechanism of action. For this purpose, using the isolated rat adrenal glands, the effects of hypoxia on CA release evoked by nicotinic ($N_1$) and muscarinic ($M_1$) receptor agonists, membrane-depolarizing agent, $Ca^{++}$-channel activator, intracellular $Ca^{++}$-releaser and ACh were determined. Experiments were carried out, perfusing Krebs solution pre-equilibrated with a gas mixture of 95% N_2$ and 5% $CO_2$. Hypoxia was maintained for $3{\sim}4$ hours through the experiments. Hypoxia gradually caused a time-dependent seduction in CA secretion evoked by DMPP ($100{\mu}M$), McN-A-343 ($100{\mu}M$), ACh (5.32 mM), Bay-K-8644 ($10{\mu}M$) and high $K^+$ (56 mM) respectively. How-ever, it did not affect CA secretion evoked by cyclopiazonic acid ($10{\mu}M$). Hypoxia itself also did fail to produce any influence on spontaneous secretory response of CA. These experimental results suggest that hypoxia depresses CA release evoked by both cholinergic stimulation and membrane-depolarization from the isolated rat adrenal medulla, and that this inhibitory activity may be due to the result of the direct inhibition of $Ca^{++}$ influx into the chromaffin cells without any effect on the calcium mobilization from the intracellular store.

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Antioxidant Effects of Eriodictyol on Hydrogen Peroxide-Induced Oxidative Stress in HepG2 Cells (산화스트레스가 유도된 HepG2 세포에서 Eriodictyol의 항산화 효과)

  • Joo, Tae-Woo;Hong, Sung-Hyun;Park, Sun-Young;Kim, Gur-Yoo;Jhoo, Jin-Woo
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.4
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    • pp.510-517
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    • 2016
  • This study was conducted to investigate the antioxidant and hepatoprotective effects of eriodictyol compound against hydrogen peroxide-induced oxidative stress in HepG2 cells by measuring expression levels of antioxidant enzymes, liver function index enzyme activities, and inhibitory effects against reactive oxygen species (ROS) production. HepG2 cell viability was assessed using 3-(4,5-dimethyl thiazole-2-yl)-2,5-diphenyl tetrazolium bromide assay. In the concentration range of $10{\sim}50{\mu}g/mL$, eriodictyol displayed over 98% cell viability in HepG2 cells. The effects of increased gene expression on hydrogen peroxide-induced oxidative stress were analyzed by monitoring antioxidant enzyme (superoxide dismutase, SOD; catalase, CAT; glutathione peroxidase, GPx) gene expression levels using real-time PCR. Eriodictyol compound significantly increased gene expression levels of SOD, CAT, and GPx in a dose-dependent manner ($10{\sim}50{\mu}g/mL$). Hepatoprotective effects against hydrogen peroxide-induced oxidative stress were analyzed by monitoring glutamic oxaloacetic transaminase (GOT), lactate dehydrogenase (LDH), and gamma-glutamyl transferase (GGT) activities in HepG2 cell culture medium using a biochemistry analyzer. Eriodictyol compound significantly reduced GOT, LDH, and GGT activities in a dose-dependent manner in HepG2 cells. ROS level in HepG2 cells was analyzed by 2',7'-dichlorofluorescein fluorescence diacetate assay, and eriodictyol compound effectively reduced the intracellular ROS level in HepG2 cells. The results reveal that eriodictyol compound can be useful for development of effective antioxidant and hepatoprotective agents.

Biodegradation Characteristics of Monochlorophenols by Wood Rot Fungi (Monochlorophenol의 목질분해균에 의한 분해 특성)

  • Choi, In-Gyu;Lee, Jae-Won;Choi, Don-Ha
    • Korean Journal of Environmental Agriculture
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    • v.21 no.4
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    • pp.261-268
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    • 2002
  • Biodegradation of monochlorophenols by wood rot fungi such as Daldina concentrica, Trametes versicolor and Pleurotus ostreatus was evaluated by determining their resistance or toxic test and biodegradability. The metabolites of monochlorophenols were also analyzed. Among the three fungi, T. versicolor was the most resistant to 200 ppm of 2-, 3- and 4-chlorophenols, and did not show any inhibitory mycellium growth. But D. concentrica had a little inhibition effect at more than 100 ppm of 3- or 4-chlorophenol. Control cultures of P. ostreatus took even 14 days far the completion of mycellium growth, but the hyphal growth was improved when 2- or 3-chlorophenol were added to the culture. In biodegradation analysis, P. ostreatus showed the highest degradation of 2- or 3-chlorophenol, while T. versicolor was the most effective in 4-chlorophenol. D. concentrica and P. ostreatus slowly degraded 4-chlorophenol. However, T. versicolor had similar degradation capability in the three monochlorophenols, suggesting that the biode- gradation nude is dependent on the fungi as well as the type of monochlorophenol. Several metabolites such as 1,3,5-trihydroxyl benzene, 1-ethyl-1-hydroxyl pentane, 2-propenoicacid, methylmalonic acid and 2-methyl-4-keto-pentan-2-ol were found as products of primary oxidation of 2-, 3- and 4-chlorophenols by intact fungal cultures. fatty acids including tetradecanoic, heptadecanoic and octadecanoic acids were also detected The order of increase of mycellium weight during incubation were P. ostreatus > T. versicolor > D. concentrica. The pH in the culture was not constantly changed depending on incubation days, but the mycellium weight was slightly increased, indicating that the biodegradation of monochlorophenol might have low relationship with the mycellium growth Laccase activities of T. versicolor and P. ostreatus were continuously increased depending on the incubation days, suggesting that the ligninolytic enzyme activity play an important role in the biodegradation of monochlorophenol.

Neuroprotective effects of cultured and fermented wild ginseng extracts on oxidative stress induced by hydrogen peroxide in PC12 cells (발효산삼배양근농축액의 산화방지 효과 및 과산화수소로 유발된 PC12 세포독성 보호효과)

  • Choi, Yeo Ok;Kim, Yu-Ri;Shin, Seung-Yong;Lee, Jae Geun;Kim, Chul Joong;Lee, Ye ji;Kang, Byeongju;Kim, Gwansu;Choi, Jee Eun;Han, Beom-Seok
    • Korean Journal of Food Science and Technology
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    • v.50 no.4
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    • pp.383-390
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    • 2018
  • Most neurodegenerative diseases are known to be influenced by oxidative stress. We investigated the anti-oxidative activity of the concentrate of fermented wild ginseng root culture (HLJG0701) containing ginsenosides Rg5 and Rk1. HLJG0701 showed effective DPPH and ABTS radical scavenging ability ($IC_{50}$: 16- and 4-fold dilution, respectively) and was inhibited dose-dependently by the $FeSO_4$-induced lipid peroxidation group (8- and 4-fold dilution: 2.3 and 1.5 nM, respectively). In MTT and LDH assays, 8-, 16-, 32- and 64-fold diluted HLJG0701 significantly increased cell viability by 70, 53, 35, and 26%, respectively. LDH released by HLJG0701 was reduced 1.3-fold with 8-fold diluted HLJG0701 compared to the $H_2O_2$-treated control. In addition, the inhibitory effect of HLJG0701 on oxidative stress in PC12 cells was confirmed by DCF-DA analysis (16-, 4-fold diluted HLJG0701: 50 and 68% ROS inhibition, respectively), TBARS (16- and 4-fold diluted HLJG0701: 50.7 and 46.5% inhibition, respectively), GPx (16- and 4-fold diluted HLJG0701: 133.3 and 227.3% release, respectively), and SOD analysis (16- and 4-fold diluted HLJG0701: 118.2 and 218.2% release, respectively). These results suggested that HLJG0701 protects neuronal cells by its anti-oxidative effects and hence can be a potential preventive material against neurodegenerative diseases.

Cytotoxicities of Hydrolyzed Crude Laminaran from Eisenia bicyclis on the SNU-1, HeLa and SW Cells (대황으로부터 추출한 crude laminaran 가수분해물의 암 세포독성)

  • Do, Jeong-Ryong;Kim, Dong-Soo;Park, Jong-Hyuk;Kim, Young-Myung
    • Korean Journal of Food Science and Technology
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    • v.38 no.6
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    • pp.793-798
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    • 2006
  • We investigated the effects on the cytotoxicity against several cancer cells of the hydrolysis and molecular weight fractionation of crude laminaran from E. bicyclis, a brown seaweed collected from Uleung island in Korea, was extracted with boiling water and then crude laminaran was prepared by ethanol precipitation of extract obtained after elimination of calcium alginate by calcium chloride. Crude laminaran was hydrolyzed by enzyme (Econase CE), acid (0.1 N HCl) and autoclaving ($121^{\circ}C$, 180 min), and the molecular weight fractions by ultrafiltration to generate molecular weight fractions. Total sugar and sulfate contents of hydrolyzed laminaran were 72.3 and 3.5% (enzyme hydrolysate), 68.5 and 3.0% (acid hydrolysate), 70.2 and 3.2% (autoclaved), and monosaccharides of which consisted of glucose (74.7-78.5%), mannose (9.9-11.5%), galactose (8.5-9.6%) and fucose (3.1-4.5%), respectively. When the cytotoxicity of hydrolyzed laminaran on SNU-1, HeLa and SW cells was evaluated by MTT assay, growth-inhibitory activity of the enzyme hydrolysate against cancer cells was higher than that of acid hydrolysate or autoclaved laminaran. Furthermore, the fraction at a molecular weight range of 10 to 50 kDa revealed higher anti-proliferative activities. The $IC_{50}$ values of 10-50 kDa fraction at a molecular weight range of 10 to 50 kDa revealed higher anti-proliferative activities. The $IC_{50}$ values of 10-50 kDa fractions on SNU-1, HeLa and SW cells were 60.4, 58.6 and 53.9 ${\mu}g/mL$ for enzymatic hydrolysate, 75.6, 73.5 and 77.4 ${\mu}g/mL$ for acid hydrolysate, and 61.7, 68.2 and 60.8 ${\mu}g/mL$ for autoclaved, respectively.

Antimutagenic Effects of Korean Bamboo Trees and Inhibitory Effect of Hepatic Toxicity of Bamboo Extracts Coated Rice (한국산 대나무의 항돌연변이 효과 및 대나무 코팅쌀의 간 독성 억제효과)

  • Lee, Min-Ja;Kim, Eun-Young;Jeong, Keun-Ok;Park, Kun-Young;Moon, Gap-Soon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.33 no.8
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    • pp.1279-1285
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    • 2004
  • To evaluate the antimutagenic effect and hepato protective of bamboo trees and bamboo byproduct, hot-water extracts from four kinds of bamboo [wang-dae (Phyllostachys bambusoides S. et Z.), som-dae (Phyllostachys nigra var. henonis), maengjong-juk (Phyllostachys pubescens) and o-juk (Phyllostachys nigra Munro)] and maengjong-juk extract coated rice were evaluated for antimutagenicity by Ames test using Salmonella typhimurium TA100. Bamboo extracts showed strong antimutagenic activity in the Ames test which MNNG was used as mutagen in the absence and presence of S9 mix. Maengjong-juk extract coated rice diet suppressed the loss of body weight significantly. Food intake was increased in maengjong-juk extract coated rice supplemented group but showed no significant differences between control and maengjong-juk extract coated rice diet groups. Food efficiency of maengjong-juk extract coated rice supplemented group was significantly higher than that of the control group. Liver weight was significantly increased by maengjong-juk extract coated rice diet administration. Plasma GOT & GPT activities of rabbit were significantly suppressed in maengjong-juk extract coated rice supplemented group. These results suggest that bamboo trees extracts and maengjong-juk extract coated rice are bioavailable resource on treatment of cardiovascular disease, such as atherosclerosis and hypercholesterolemia.

Inhibition of Adipocyte Differentiation and Adipogenesis by Aged Black Garlic Extracts in 3T3-L1 Preadipocytes (흑마늘 추출물에 의한 3T3-L1 지방전구세포의 분화 및 adipogenesis 억제에 관한 연구)

  • Park, Jung-Ae;Park, Cheol;Han, Min-Ho;Kim, Byung-Woo;Chung, Yoon-Ho;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.21 no.5
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    • pp.720-728
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    • 2011
  • Garlic (Allium sativum) has been used as a source food as well as a traditional folk medicine ingredient since ancient times. Aged black garlic is a type of fermented garlic and is expected to have stronger anticancer and antioxidant activities than raw garlic. However, the mechanisms of their inhibitory effects on adipocyte differentiation and adipogenesis are poorly understood. In the present study, the effects and mechanisms of water extracts of raw garlic (WERG) and aged black garlic (WEABG) on adipocyte differentiation and adipogenesis in 3T3-L1 preadipocytes were investigated. Treatment with WEABG significantly suppressed terminal differentiation of 3T3-L1 preadipocytes in a dose-dependent manner as confirmed by a decrease in lipid droplet number and lipid content through Oil Red O staining, however WERG had no such effect. In addition, WEABG reduced accumulation of cellular triglyceride, which is associated with a significant inhibition of key pro-adipogenic transcription factors including peroxisome proliferator-activated receptor ${\gamma}$ (PPAR${\gamma}$), cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT)/enhancer binding proteins ${\alpha}$ (C/EBP${\alpha}$) and C/EBP${\beta}$. Taken together, these results provide important new insight that aged black garlic might inhibit adipogenesis by suppressing the pro-adipogenic transcription factors in 3T3-L1 preadipocytes, and further studies will be needed to identify the active compounds that confer the anti-obesity activity of aged black garlic.

Inhibitory Mechanisms of Cell Cycle Regulation Induced by Indole-3-carbinol in Hepatocellular Carci-noma HepG2 Cells. (간암 세포주에서의 Indole-3-Carbinol에 의해 유도되는 세포주기 억제 기전)

  • 김동우;이광수;김민경;조율희;이철훈
    • Microbiology and Biotechnology Letters
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    • v.29 no.3
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    • pp.181-185
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    • 2001
  • The naturally occurring chemical indole-3-carbinol (13C), found in vegetables of the Brassica genus, is a promising anticancer agent that was shown previ- ously to induce a Gl cell cycle arrest of human breast cancer cell lines, independent of estrogen receptor signaling. The anticancer activity of 13C and the possible mechanisms of its action were explored in a human hepatocellular carcinoma cell line, HepG2. Treatment of HepG2 cells with 13C suppressed the growth of the cells. The growth sup- pression caused by 13C ($IC_{50}$/: 444$\mu$M) was found to be partially due to its ability to stop the cell cycle in HepG2 cells. Western blot analysis for the Gl phase artiest demonstrated that the expression-levels of cyclin-dependent kinase (Cdk4, Cdk6) and cyclic D were reduced strongly after treatment of Hep72 cells with 13C (4007M) for 24- 72 hrs. Furthermore, I3C selectively abolished the expression of Cdk6 in a dose- and time-dependent manner, and accordingly, inhibited the phosphorylation of retinoblastoma. Interestingly, after the HepG2 cells reached their max- imal growth arrest, the level of the p21, a well-known Cdk inhibitor, increased significantly. Therefore, it could be considered that the Gl arrest of HepG2 cells treated with 13C was due to the indirect inhibition of Cdk4/6 activities by p21 Western blot analysis for G2/M phase arrest of demonstrated the levels of Cdc2 and cyclin Bl werer reduced dramatically after the treatment of HepG2 cells with 13C ($40\mu$M) for 24-72 hrs. flow cytometry of propidium iodide-stained HepG2 cells revealed that 13C induces a Gl (53%,72hr incubation) and G2 (25%,24hr incubation) cell cycle arrest. Thus, our observations have uncovered a previously undefined antiproliferative pathway for r3C that implicates Cdk4/6 and Cdc2 as a target for cell cycle control in human HepG2 cells. However, the 13C-medi- ated cell cycle arrest and repression of Cdk4/6 production did not affect the apoptotic induction of HepG2 cell.

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Anti-Inflammatory Effect of Wheat Germ Oil on Lipopolysaccharide-stimulated RAW 264.7 Cells and Mouse Ear Edema (LPS로 유도한 RAW 264.7 세포 및 귀부종 동물 모델에 대한 밀배아유의 항염증 효과)

  • Kang, Bo-Kyeong;Kim, Min-Ji;Jeong, Da-Hyun;Kim, Koth-Bong-Woo-Ri;Bae, Nan-Young;Park, Ji-Hye;Park, Sun-Hee;Ahn, Dong-Hyun
    • Microbiology and Biotechnology Letters
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    • v.44 no.3
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    • pp.236-245
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    • 2016
  • This study investigated the anti-inflammatory effects of wheat germ oil (WGO) on RAW 264.7 cells. It was shown that WGO had no cytotoxicity against the treated cells or negative effect on their proliferation. WGO suppressed nitric oxide (NO) secretion considerably and had inhibitory effects on the production of LPS-induced NO and pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β). In particular, the IL-6 and TNF-α inhibition activities were over 90% at 100 μg/ml concentration of the oil. WGO also inhibited the LPS-induced expression of cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor-kappa B (NF-κB), and reduced the expression of phosphorylated ERK and JNK. Moreover, the croton-oil-induced edema in mouse ears was reduced by WGO, and no mortalities occurred in mice administered 5,000 mg/kg body weight of WGO over a 2-week observation period. In conclusion, these results provide evidence for the anti-inflammatory effect of WGO that likely occurs via modulation of NF-κB and the JNK/ERK MAPK signaling pathway.