• Title/Summary/Keyword: Glycation

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Oxidative damage of DNA induced by the reaction of methylglyoxal with lysine in the presence of ferritin

  • An, Sung Ho;Kang, Jung Hoon
    • BMB Reports
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    • v.46 no.4
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    • pp.225-229
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    • 2013
  • Methylglyoxal (MG) is an endogenous metabolite which is present in increased concentrations in diabetics and reacts with amino acids to form advanced glycation end products. In this study, we investigated whether ferritin enhances DNA cleavage by the reaction of MG with lysine. When plasmid DNA was incubated with MG and lysine in the presence of ferritin, DNA strand breakage was increased in a dose-dependent manner. The ferritin/MG/lysine system-mediated DNA cleavage was significantly inhibited by reactive oxygen species (ROS) scavengers. These results indicated that ROS might participate in the ferritin/MG/lysine system-mediated DNA cleavage. Incubation of ferritin with MG and lysine resulted in a time-dependent release of iron ions from the protein molecules. Our data suggest that DNA cleavage caused by the ferritin/MG/lysine system via the generation of ROS by the Fenton-like reaction of free iron ions released from oxidatively damaged ferritin.

RAGE-binding peptide-conjugated polyethylenimine as a dual-functional carrier: A RAGE-mediated gene carrier and an anti-angiogenic reagent

  • Lee, Dahee;Choi, Eunji;Lee, Jaewon;Oh, Jungju;Lee, Seonyeong;Lee, Minhyung
    • Journal of Industrial and Engineering Chemistry
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    • v.67
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    • pp.284-292
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    • 2018
  • Receptor for advanced glycation end-products (RAGE) is overexpressed in various cancer cells. In this study, a RAGE-binding peptide (RBP) was conjugated to polyethylenimine (25 kDa, PEI). RBP-conjugated PEI (PEI-RBP) was characterized as a dual-functional reagent, a RAGE-mediated gene carrier and an anti-angiogenic reagent. As a gene carrier, PEI-RBP had higher transfection efficiency to the C6 glioblastoma cells than PEI. As an anti-angiogenic reagent, the pEmpty/PEI-RBP complex reduced RAGE expression on the surface of the C6 glioblastoma cells. Also, the complex reduced the VEGF expression and tube formation of endothelial cells. Therefore, PEI-RBP may be useful for development of glioblastoma therapy.

Characterization of Anti-Advanced Glycation End Products (AGEs) and Radical Scavenging Constituents from Ainsliaea acerifolia (단풍취의 최종당화산물 생성 저해 및 라디칼 소거 물질의 동정)

  • Jeong, Gyeng Han;Kim, Tae Hoon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.6
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    • pp.759-764
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    • 2017
  • Reactive oxygen species (ROS) and advanced glycation end products (AGEs) are valuable therapeutic targets for the regulation of diabetic complications. Activity-guided isolation of the ethylacetate (EtOAc)-soluble portion of 70% ethanolic extract from aerial parts of Ainsliaea acerifolia was performed, followed by AGE formation inhibition assay for the characterization of four dicaffeoylquinic acid derivatives of a previously known structure, methyl 3,5-di-O-caffeoyl-epi-quinate (1), 3,5-di-O-caffeoyl-epi-quinic acid (2), 4,5-di-O-caffeoyl-quinic acid (3), and methyl 4,5-di-O-caffeoyl-quinate (4). The structures of these compounds were confirmed by interpretation of nuclear magnetic resonance (NMR, $^1H-$, $^{13}C-NMR$, two-dimensional NMR) and mass spectroscopic data. Among the isolates, the major secondary metabolites, 3,5-di-O-caffeoyl-epi-quinic acid (2) and 4,5-di-O-caffeoyl-quinic acid (3) showed the most potent inhibitory effects against AGE formation with $IC_{50}$ values of $0.6{\pm}0.1{\mu}M$ and $0.4{\pm}0.1{\mu}M$, respectively. Furthermore, all isolated dicaffeoylquinic acid derivatives were evaluated for their radical scavenging activities using 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical, and compound 3 exhibited the most potent inhibitory effect in a concentration-dependent manner. This result suggests that the caffeoylquinic acid dimers isolated from A. acerifolia might be beneficial for the prevention of diabetic complications and related diseases.

Inhibitory effects of advanced glycation end products formation and free radical scavenging activity of Cirsium setidens (곤드레 추출물의 최종당화산물의 생성저해 및 라디칼소거 활성)

  • Kim, Taewan;Lee, Jaemin;Jeong, Gyeong Han;Kim, Tae Hoon
    • Food Science and Preservation
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    • v.23 no.2
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    • pp.283-289
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    • 2016
  • Naturally occurring antioxidants, such as polyphenols are widely found in fruits, vegetables, wines, juices, and other plant-based dietary sources and are divided into several sub classes, including phenylpropanoids, flavonoids, stilbenoids, and lignans. As part of the our ongoing search for bioactive food ingredients, the antioxidant and advanced glycation end products (AGEs) formation inhibitory activities of the methanolic extract of the aerial parts of Cirsium setidens were investigated in vitro bioassay system. The antioxidant properties were evaluated through radical scavenging assays using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) ($ABTS^+$) radicals. In addition, the activity of C. setidens against diabetes complications was also tested via AGEs formation inhibition assay. The total phenolic contents were determined using a UV-VIS spectrophotometric method. All tested samples showed a dose-dependent radical scavenging and AGEs inhibitory activities. In particular, the n-butanol (BuOH)-soluble portion showed the most potent radical scavenging activities against DPPH and $ABTS^+$ radicals with $IC_{50}$ values of $24.3{\pm}1.7$ and $25.0{\pm}3.3{\mu}g/mL$, respectively. Futhermore, the inhibition of AGEs formation by the n-BuOH-soluble portion ($IC_{50}$ value; $46.0{\pm}1.5{\mu}g/mL$) was higher than that those of the soluble portions for the other solvent. The results showed that C. setidens could be considered as an effective source of natural antioxidants and other ingredients.

Effect of Reactive Oxygen Species on the Formation of Nε-(carboxymethyl)lysine, an Endproduct of Maillard Reaction of Proteins (단백질의 Maillard 반응의 최종산물인 CML 형성에 미치는 ROS의 영향)

  • Lee, Jong-Sun;Yang, Ryung;Shin, Dong-Bum
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.33 no.1
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    • pp.123-131
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    • 2004
  • The effect of reactive oxygen species (ROS) on the formation of $N^{\varepsilon}$-(carboxymethly)lysine (CML). one of the endproducts in the Maillard reaction of protein (or glycation), was investigated. Glyoxal, a main precursor of CML formation, was produced from both glucose and fructose during their autoxidation. The transition metal ion showed to involve in the formation of glyoxal by the metal catalyzed oxidation, suggesting that ROS accelerated the reducing sugar autoxidation. The stimulative effect of ROS on the autoxidation was more prominent in glucose than in fructose. Polyunsaturated acids (PUFAs) were shown to form glyoxal by peroxidation in proportion to the degree of unsaturation, but ROS did not affect on PUFA peroxidation. Ascorbic acid also lysine (CMHL) in the model system using hippuryl lysine and glucose had a significant effect on ROS, whereas it had no effect on ROS using glyoxal as a reactant. Almost the same trend was obtained by the analysis of antigen coated indirect noncompetitive ELISA using monoclonal antibody (6D12). These data indicated that ROS affected glucose autoxidation as well as mediated both CML and glyoxal formation, but did not affect the reactive compounds such as fructose, PUFAs and ascorbic acid.

Antioxidant and Physiological Activities of Capsicum annuum Ethanol Extracts (고추 에탄올 추출물의 항산화 효과 및 생리활성에 관한 연구)

  • Kim, Hun-Joong;Hong, Chung-Oui;Nam, Mi-Hyun;Ha, Young-Min;Lee, Kwang-Won
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.6
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    • pp.727-732
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    • 2012
  • The goal of this study is to determine the activities of antioxidants and antiglycation from the extracts of various Capsicum annum (known as pepper) ethanolic extract (CAE). We tested the extracts of Capsicum annum seeds and pericarps using 70% ethanol. The CAE showed antioxidant activities in a 2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radical cation assay, 1,1-diphenyl-2-picrylhydrazyl free radical-scavenging assay, ferric-reducing antioxidant power assay, total flavonoid content, and total polyphenol content. Also, the physiological activities of CAE on glycation inhibition activities, anti-${\alpha}$-glucosidase activities, and tyrosinase activities were measured. As a result, green and red Capsicum annuum seeds show higher levels of antioxidant activities. In addition, the physiological activities are also more effective in the seeds than in the plant pericarps. A radar chart proves that antioxidants and physiological activities are more effective coming from the seeds. And the red Capsicum annuum seeds are more effective than the green ones.

Preventive effects of crocin on neuronal damages induced by D-galactose through AGEs and oxidative stress in human neuroblastoma cells (SH-SY5Y)

  • Heidari, Somaye;Mehri, Soghra;Shariaty, Vahidesadat;Hosseinzadeh, Hossein
    • Journal of Pharmacopuncture
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    • v.21 no.1
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    • pp.18-25
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    • 2018
  • Objective: D-galactose (D-gal) is well-known agent to induce aging process. In the present study, we selected crocin, the main constituent of Crocus sativus L. (saffron), against D-gal- induced cytotoxicity in human neuroblastoma SH-SY5Y cells. Methods: Pretreated cells with crocin ($25-500{\mu}M$, 24 h) were exposed to D-gal (25-400 mM, 48 h). The MTT assay was used for determination cell viability. Dichlorofluorescin diacetate assay (DCF-DA) and senescence associated ${\beta}$-galactosidase staining assay (SA-${\beta}$-gal) were used to evaluate the generation of reactive oxygen species and beta-galactosidase as an aging marker, respectively. Also advanced glycation end products (AGEs) expression which is known as the main mechanism of age-related diseases was measured by western blot analysis. Results: The findings of our study showed that treatment of cells with D-gal (25-400 mM) for 48h decreased cell viability concentration dependency. Reactive oxygen species (ROS) levels which are known as main factors in age-related diseases increased from $100{\pm}8%$ in control group to $132{\pm}22%$ in D-gal (200 mM) treated cells for 48h. The cytotoxic effects of D-gal decreased with 24h crocin pretreatment of cells. The cell viability at concentrations of $100{\mu}M$, $200{\mu}M$ and $500{\mu}M$ increased and ROS production decreased at concentrations of 200 and $500{\mu}M$ to $111.5{\pm}6%$ and $108{\pm}5%$, respectively. Also lysosomal biomarker of aging and carboxymethyl lysine (CML) expression as an AGE protein, significantly increased in D-gal 200 mM group after 48h incubation compare to control group. Pre-treatment of SHSY-5Y cells with crocin ($500{\mu}M$) before adding D-gal significantly reduced aging marker and CML formation. Conclusion: Treatment of SH-SY5Y cells with crocin before adding of D-gal restored aging effects of D-gal concentration dependency. These findings indicate that crocin has potent anti- aging effects through inhibition of AGEs and ROS production.

Anti-diabetic and Anti-oxidative Activities of Extracts from Crataegus pinnatifida (산사 추출물의 항산화 및 항당뇨 활성)

  • Nam, Sang-Myeoung;Kang, Il-Jun;Shin, Mee-Hye
    • Journal of the East Asian Society of Dietary Life
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    • v.25 no.2
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    • pp.270-277
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    • 2015
  • This study was performed to investigate the antidiabetic and antioxidant activities of Crataegus pinnatifida which was extracted with water and different concentrations of EtOH (0~100%). The extraction yield of 70% EtOH (33.16%) was higher than that of 50% EtOH (27.79%), water (21.71%), 30% EtOH (21.88%) and 100% EtOH (19.03%). Total polyphenol contents of 50% EtOH extract from C. pinnatifida were the highest. DPPH and ABTS radical scavenging activities were $80.79{\pm}0.83%$ and $34.92{\pm}0.97%$ in 50% EtOH extract, respectively, which were higher than those of other extracts. The inhibitory activities of 50% ethanol extract from C. pinnatifida against advanced glycation end products (AGEs) formation and ${\alpha}$-glucosidase were determined to be $27.09{\pm}2.27%$ and $58.87{\pm}0.70%$, respectively. The inhibitory activity of water extract from C. pinnatifida against aldose reductase was higher ($30.68{\pm}1.41%$) than those of other extracts. Overall, 50% EtOH extract from C. pinnatifida showed the highest antidiabetic and antioxidant effects. These results suggest that 50% ethanol extracts from C. pinnatifida have potential as a useful ingredient with antidiabetic and antioxidant effects.

Degraded Products Induced by Gamma-Irradiation of Mangiferin with Anti-Diabetic Complication Effects (감마선 조사에 의한 Mangiferin 변화물의 항당뇨합병증 활성)

  • Jeong, Gyeong Han;Kim, Tae Hoon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.11
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    • pp.1414-1418
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    • 2017
  • Inhibition of advanced glycation end product (AGE) formation is a valuable therapeutic strategy for the regulation of diabetic complications. This study was conducted to identify potential therapeutic targets of anti-diabetic complications from irradiated mangiferin using AGE formation assay. Radiolytic degradation of the xanthone glucoside mangiferin by gamma-irradiation resulted in three degraded mangiferin analogues: mangiferdiol (1), mangiferinol (2), and isomangiferinol (3). Structures of the three newly generated compounds were characterized by interpretation of nuclear magnetic resonance ($^1H$, $^{13}C$ NMR, $^1H-^1H$ COSY, HSQC, HMBC, and NOESY) and mass spectroscopic data. The anti-diabetic complication of the generated mangiferin derivatives were tested using in vitro AGE formation method. Among the tested degraded products, mangiferinol (2) and isomangiferinol (3) exhibited significantly improved potency against AGE formation inhibitory activities with $IC_{50}$ values of $5.6{\pm}0.8$ and $7.6{\pm}0.9{\mu}M$, respectively. This result implies that xanthone derivatives generated from gamma-irradiated mangiferin might be beneficial for prevention of diabetic complication and related diseases.

Anti-aging Effects of Prescription Extracts Containing Forsythia viridissima L. (연교를 함유한 처방단 추출물의 항노화 효과)

  • Kim, Mi Jin;Jung, Taek Kyu;Yoon, Kyung-Sup
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.41 no.1
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    • pp.85-96
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    • 2015
  • Forsythia fructus has been shown to have antioxidative, anti-inflammatory, antibacterial, anti-aging and whitening effects. This work was carried out to investigate the anti-aging effects of Forsythia viridissima-prescription extracts (Yeongyoseungma-tang, Gamiyeongyoseungma-tang, Hoechunyangkyeok-san) on skin. Skin anti-aging effect of Forsythia viridissima-prescription extracts (Yeongyoseungma-tang, Gamiyeongyoseungma-tang, Hoechunyangkyeok-san) was evaluated by using antioxidant assay, anti-glycation activity, inhibitory effect of tyrosinase activity, expression of type I procollagen and UVA-induced matrix metalloproteinase-1 on HS68 cells, and reduction of ${\alpha}$-MSH-induced melanin on B16F1 cells. Forsythia viridissima-prescription extracts showed anti-oxidative and anti-glycation activity. The pectinex hydrolysed extract from Yeongyoseungma-tang 75% EtOH extract and Gamiyeongyoseungma-tang 75% EtOH extract increased the type I procollagen synthesis, and decreased the UVA-induced MMP-1 expression on HS68 cells. The pectinex hydrolysed extracts of Hoechunyangkyeok-san 75% EtOH extract had the inhibitory effect of melanin synthesis on B16F1 cells. Based on these results, we suggest that Forsythia viridissima-prescription extracts may be useful as a potential source of functional anti-aging cosmetics.