• 제목/요약/키워드: Inhibiting Effect

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Metformin enhances the osteogenic activity of rat bone marrow mesenchymal stem cells by inhibiting oxidative stress induced by diabetes mellitus: an in vitro and in vivo study

  • Kai Dong;Wen-Juan Zhou;Zhong-Hao Liu
    • Journal of Periodontal and Implant Science
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    • v.53 no.1
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    • pp.54-68
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    • 2023
  • Purpose: The purpose of this study was to determine whether metformin (MF) could alleviate the expresssion of reactive oxygen species (ROS) and improve the osteogenic ability of bone marrow mesenchymal stem cells derived from diabetic rats (drBMSCs) in vitro, and to evaluate the effect of MF on the ectopic osteogenesis of drBMSCs in a nude mouse model in vivo. Methods: BMSCs were extracted from normal and diabetic rats. In vitro, a cell viability assay (Cell Counting Kit-8), tests of alkaline phosphatase (ALP) activity, and western blot analysis were first used to determine the cell proliferation and osteogenic differentiation of drBMSCs that were subjected to treatment with different concentrations of MF (0, 50, 100, 200, 500 µM). The cells were then divided into 5 groups: (1) normal rat BMSCs (the BMSCs derived from normal rats group), (2) the drBMSCs group, (3) the drBMSCs + Mito-TEMPO (10 µM, ROS scavenger) group, (4) the drBMSCs + MF (200 µM) group, and (5) the drBMSCs + MF (200 µM) + H2O2 (50 µM, ROS activator) group. Intracellular ROS detection, a senescence-associated β-galactosidase assay, ALP staining, alizarin red staining, western blotting, and immunofluorescence assays were performed to determine the effects of MF on oxidative stress and osteogenic differentiation in drBMSCs. In vivo, the effect of MF on the ectopic osteogenesis of drBMSCs was evaluated in a nude mouse model. Results: MF effectively reduced ROS levels in drBMSCs. The cell proliferation, ALP activity, mineral deposition, and osteogenic-related protein expression of drBMSCs were demonstrably higher in the MF-treated group than in the non-MF-treated group. H2O2 inhibited the effects of MF. In addition, ectopic osteogenesis was significantly increased in drBMSCs treated with MF. Conclusions: MF promoted the proliferation and osteogenic differentiation of drBMSCs by inhibiting the oxidative stress induced by diabetes and enhenced the ectopic bone formation of drBMSCs in nude mice.

In Vitro α-Amylase, α-Glucosidase, Pancreatic Lipase, Xanthine Oxidase Inhibiting Activity of Agaricus bisporus Extracts

  • Jung Han Kim;Myoung Jun Jang;Youn Jin Park
    • Mycobiology
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    • v.51 no.1
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    • pp.60-66
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    • 2023
  • In this study, the α-amylase inhibitory activity, α-glucosidase inhibitory activity, pancreatic lipase inhibitory activity, and Xanthine Oxidase inhibitory activity of the fruiting body extracts of 5 varieties of Agaricus bisporus (AB) were confirmed. First, the α-amylase inhibitory activity of AB12, AB13, AB18, AB34, and AB40 methanol extracts was lower than that of acarbose, a positive control, in all concentration ranges. The α-glucosidase inhibitory activity of the AB40, AB13, and AB12 methanol extracts at the extract concentration of 1.0 mg/mL was 80.5%, 81.3%, and 78.5%, respectively, similar to that of acarbose, a positive control. The pancreatic lipase inhibitory activity of the methanol extract of Agaricus bisporus fruiting body was significantly lower than that of the positive control orlistat in the concentration range of 50~1.000 (mg/mL). The Xanthine Oxidase inhibitory activity was 0.5~8.0 mg/mL of each extract, which was significantly lower than that of the positive control allopurinol in the same concentration range. However, the Xanthine Oxidase inhibitory activity of AB13 and AB40 at 8.0 mg/mL was about 70%, which was higher than that of other mushrooms. In conclusion, five kinds of Agaricus bisporus fruiting bodies seem to have inhibitory effects on enzymes such as α-amylase, α-glucosidase, pancreatic lipase, and Xanthine Oxidase that degrade starch and protein. In particular, it has an inhibitory effect and a reduction effect on xanthine oxidase that causes gout, so it is expected that it can be developed and used as a food or health supplement with health functional properties through future research.

Aurantio-obtusin exerts an anti-inflammatory effect on acute kidney injury by inhibiting NF-κB pathway

  • Haiyan Xiang;Yun Zhang;Yan Wu;Yaling Xu;Yuanhao Hong
    • The Korean Journal of Physiology and Pharmacology
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    • v.28 no.1
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    • pp.11-19
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    • 2024
  • Acute kidney injury (AKI) is one of the major complications of sepsis. Aurantio-obtusin (AO) is an anthraquinone compound with antioxidant and anti-inflammatory activities. This study was developed to concentrate on the role and mechanism of AO in sepsis-induced AKI. Lipopolysaccharide (LPS)-stimulated human renal proximal tubular epithelial cells (HK-2) and BALB/c mice receiving cecal ligation and puncture (CLP) surgery were used to establish in vitro cell model and in vivo mouse model. HK-2 cell viability was measured using MTT assays. Histological alterations of mouse renal tissues were analyzed via hematoxylin and eosin staining. Renal function of mice was assessed by measuring the levels of serum creatinine (SCr) and blood urea nitrogen (BUN). The concentrations of pro-inflammatory cytokines in HK-2 cells and serum samples of mice were detected using corresponding ELISA kits. Protein levels of factors associated with nuclear factor kappa-B (NF-κB) pathway were measured in HK-2 cells and renal tissues by Western blotting. AO exerted no cytotoxic effect on HK-2 cells and AO dose-dependently rescued LPS-induced decrease in HK-2 cell viability. The concentrations of pro-inflammatory cytokines were increased in response to LPS or CLP treatment, and the alterations were reversed by AO treatment. For in vivo experiments, AO markedly ameliorated renal injury and reduced high levels of SCr and BUN in mice underwent CLP operation. In addition, AO administration inhibited the activation of NF-κB signaling pathway in vitro and in vivo. In conclusion, AO alleviates septic AKI by suppressing inflammatory responses through inhibiting the NF-κB pathway.

Comparison of Biological Activities of Extracts from Different Parts of Seabuckthorn (Hippophae rhamnoides L.) (비타민나무(Seabuckthorn, Hippophae rhamnoides L.) 부위별 추출물의 생리활성 비교)

  • Park, Yu-Hwa;Lim, Sang-Hyun;Ham, Hun-Ju;Jeong, Haet-Nim;Lee, Kwang-Jae;Kim, Kyung-Hee;Kim, Song-Mun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.7
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    • pp.975-979
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    • 2010
  • Biological activities of different parts (stems, leaves, roots, fruits) and solvents (water, ethanol) of seabuckthorn (Hippophae rhamnoides L.) grown in Korea were tested as follows. In the experiment of inhibiting $\alpha$-glucosidase activity, ethanol extract of Hippophae rhamnoides L. stem showed the highest inhibitory activity by 93% and the next highest was the ethanol extract of its leaf by 88.7%. In the case of these two extracts, the effect of inhibiting $\alpha$-glucosidase activity was extraordinarily great when comparing with control group, acarbose. In the experiment of inhibiting $\alpha$-amylase activity, water extract of leaf showed the highest result by 54.7%, among all extracts. Regarding anticancer effect for HT-29 cell and DU-145 cell, water extract of root showed 47.1% and 32.3% activities, respectively. The experiment on antibacterial activity showed that the ethanol extract from the leaf inhibitory activity of Clostridium butyricum, Proteus mirabilis, and Shigella flexneri which are the several food borne pathogenic strains. In future research, materials for biological activity appear isolated and purified and research should continue.

Combination Therapy of the Active KRAS-Targeting Antibody inRas37 and a PI3K Inhibitor in Pancreatic Cancer

  • Lee, Ji Eun;Woo, Min Gyu;Jung, Kyung Hee;Kang, Yeo Wool;Shin, Seung-Min;Son, Mi Kwon;Fang, Zhenghuan;Yan, Hong Hua;Park, Jung Hee;Yoon, Young-Chan;Kim, Yong-Sung;Hong, Soon-Sun
    • Biomolecules & Therapeutics
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    • v.30 no.3
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    • pp.274-283
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    • 2022
  • KRAS activating mutations, which are present in more than 90% of pancreatic cancers, drive tumor dependency on the RAS/mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways. Therefore, combined targeting of RAS/MAPK and PI3K/AKT signaling pathways may be required for optimal therapeutic effect in pancreatic cancer. However, the therapeutic efficacy of combined MAPK and PI3K/AKT signaling target inhibitors is unsatisfactory in pancreatic cancer treatment, because it is often accompanied by MAPK pathway reactivation by PI3K/AKT inhibitor. Therefore, we developed an inRas37 antibody, which directly targets the intra-cellularly activated GTP-bound form of oncogenic RAS mutation and investigated its synergistic effect in the presence of the PI3K inhibitor BEZ-235 in pancreatic cancer. In this study, inRas37 remarkably increased the drug response of BEZ-235 to pancreatic cancer cells by inhibiting MAPK reactivation. Moreover, the co-treatment synergistically inhibited cell proliferation, migration, and invasion and exhibited synergistic anticancer activity by inhibiting the MAPK and PI3K pathways. The combined administration of inRas37and BEZ-235 significantly inhibited tumor growth in mouse models. Our results demonstrated that inRas37 synergistically increased the antitumor activity of BEZ-235 by inhibiting MAPK reactivation, suggesting that inRas37 and BEZ-235 co-treatment could be a potential treatment approach for pancreatic cancer patients with KRAS mutations.

INHIBITORY EFFECT OF LACTOCOCCUS LACTIS 1370 ON THE FORMATION OF DENTAL PLAQUE IN CHILDREN (소아에서 Lactococcus lactis 1370에 의한 치태형성 억제 효과)

  • Lee, Lan-Young;Lee, Chang-Seop;Lee, Kwang-Hee;Oh, Jong-Suk;Lee, Sang-Ho
    • Journal of the korean academy of Pediatric Dentistry
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    • v.28 no.4
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    • pp.583-592
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    • 2001
  • This study was undertaken to evaluate the clinical effect of inhibiting plaque formation of Lactococcus lactis 1370, a acid producing bacterium residing in the mouth. 30 children were asked to use 10ml of control mouth-wash and mouthwash containing Lactococcus lactis 1370. The plaque index and plaque area rate at 24h and 48h after the use of the mouthwashes were measured. And the number of Lactococcus lactis 1370 was counted at 1h, 3h, and 6h in the mouth. The results are as follow. 1. The mean plaque index at 24h after the use of the control mouthwash and the mouthwash containing Lactococcus lactis 1370 were 2.43 and 2.06, respectively. The inhibiting rate of plaque formation was 15% (P<0.05). 2. The mean plaque index at 48h after the use of the control mouthwash and the mouthwash containing Lactococcus lactis 1370 were 2.95 and 2.17, respectively. The inhibiting rate of plaque formation was 26%, showing more decrease than at 24h(P<0.05). 3. The mean plaque area rate at 24h after the use of the control mouthwash and the mouthwash containing Lactococcus lactis 1370 were 21.2% and 15.6%, respectively. The inhibiting rate of plaque formation was 26% (P<0.05). 4. The mean plaque area rate at 48h after the use of the control mouthwash and the mouthwash containing Lactococcus lactis 1370 were 33.0% and 17.8%, respectively. The inhibiting rate of plaque formation was 46% (P<0.05). 5. The number of Lactococcus lactis 1370 in the mouth decreased significantly from mouthwashing to 3h, but increased slightly between 3h and 6h. As seen with the above results, we think that using the mouth wash with Lactococcus lactis 1370 would prevent the formation of plaque in the mouth and can be an effective method to prevent dental caries and periodontal disease.

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The Whitening Effect by Water Extracts of Bombyx Mori Linne (백강잠(Bombyx Mori Linne) 물추출물의 미백 효능)

  • Ann, Young-Hee;Choi, Jeung-Sook
    • Journal of the Korean Society of Fashion and Beauty
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    • v.4 no.4 s.10
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    • pp.81-86
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    • 2006
  • Numerous novel ingredients have been introduced for the hight functionality of whitening cosmetics. Tough the preliminary research, we have found water extracts Bombyx mori have high whitening efficacy. The results of the research for the whitening effect of Bombyx Mori L. are as follow 1. Bombyx Mori L. inhibited concentration dependently the generation of melanin increased by the stimulation of $\alpha$-MSH and protoporphyrin IX, and $IC_{50}$ value was 8.3, 9.2 ${\mu}M$ respectively. 2. Melanin increased by the stimulation of $\alpha$-MSH and protoporphyrin IX was five to seven times superior in the inhibiting effect, compared with kojic acid used as positive control group. 3. Bombyx Mori L. did not have a decolorizing effect on melanin already generated. 3. Bombyx Mori L. was observed to have toxicity of over 100 ${\mu}M$ for the mouse melanoma B16 cells. Therefore, These results suggest that water extracts of Bombyx mori have inhibitory activity against mushroom tyrosinase and inhibitory activity of melanin synthesis in B16 melanoma cells in vitro.

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Effect of Probenecid on Tetraethylammonium (TEA) Transport Across Basolateral Membrane of Rabbit Proximal Tubule

  • Choi, Tae-Ryong;Kim, Yong-Keun
    • The Korean Journal of Physiology
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    • v.30 no.2
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    • pp.249-256
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    • 1996
  • The effect of probenecid on the transport of tetraethylammonium (TEA) was studied in renal cortical slices and isolated membrane vesicles to investigate the interaction of organic anion with the organic cation transport system in proximal tubule. Probenecid reversibly inhibited TEA uptake by renal cortical slices in a dose-dependent manner over the concentration range of 1 and 5 mM. The efflux of TEA was not affected by the presence of 3 mM probenecid. Kinetic analysis indicated that probenecid decreased Vmax without significant change in Km. Probenecid inhibited significantly tissue oxygen consumption at concentrations of 3 and 5 mM. However, probenecid did not significantly reduce TEA uptake in brush border and basolateral membrane vesicles prepared from renal cortex even at a concentration as high as 10 mM. These results indicate that probenecid reduces TEA uptake in cortical slices by inhibiting tissue metabolism rather than by an interaction with the organic ration transporter.

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Antioxidant Effect of Flavonoids Isolated from the Root of Clematis trichotoma Nakai

  • Hung, Tran Manh;Thuong, Phuong Thien;Bae, Ki-Hwan
    • Korean Journal of Medicinal Crop Science
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    • v.13 no.5
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    • pp.227-232
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    • 2005
  • The antioxidant effect of methanol extract (ME) and water extract (WE) from Clematis trichotoma was evaluated as primary study to scavenge stable 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH), inhibited iron-induce lipid peroxidation in linoleic acid emulsion, peroxidation of liposome induced by $Fe^{3+}/H_2O_2/ascorbie$ acid, and on $Fe^{2+}/H_2O_2$ induced the mitochondrial lipid peroxidation. In secondary study, five flavonoids as luteolin (1), quercetin (2), apigenin (3), hirsutrin (4), kaempferol-3-O-glucoside were isolated (5). Among them, compounds 1 and 2 showed good activities in all the model systems. Compound 3 exhibited moderate antioxidant activities in both radical scavenging and these lipid peroxidation systems tested. Compound 4 showed significant inhibitions in liposome peroxidation and compound 5 displayed weak inhibition in all four tested systems. All the results presented herein indicate that products of C. trichotoma maybe useful in inhibiting membrane lipid peroxidation and preventing free radical-linked diseases.

Hypoglycemic Effect of Sargassum ringgoldianum Extract in STZ-induced Diabetic Mice

  • Lee, Chae-Won;Han, Ji-Sook
    • Preventive Nutrition and Food Science
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    • v.17 no.1
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    • pp.8-13
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    • 2012
  • This study was designed to investigate whether Sargassum ringgoldianum extract may inhibit ${\alpha}$-glucosidase and ${\alpha}$-amylase activities, and alleviate postprandial hyperglycemia in streptozotocin-induced diabetic mice. The $IC_{50}$ values of Sargassum ringgoldianum extract against ${\alpha}$-glucosidase and ${\alpha}$-amylase were 0.12 mg/mL and 0.18 mg/mL, respectively, which evidenced higher activities than those of acarbose. The blood glucose levels of the Sargassum ringgoldianum extract administered group were significantly lower compared to the control group in the streptozotocin-induced diabetic mice. Moreover, the area under the two-hour blood glucose response curve was significantly reduced and the absorption of dietary carbohydrates was delayed after administration of Sargassum ringgoldianum extract in the diabetic mice. Therefore, these results indicated that Sargassum ringgoldianum extract may help decrease the postprandial blood glucose level via inhibiting ${\alpha}$-glucosidase.