• Title/Summary/Keyword: advanced glycation end-products

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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.

Fucoidan Reduces Cellular and Mitochondrial Injury and Improves Impaired Osteogenic Activity in MC3T3-E1 Cells Treated with Advanced Glycation End-products (MC3T3-E1 세포에서 최종당산화물에 의한 세포와 미토콘드리아 손상, 조골세포 분화능, 조골 및 파골 활동성 변화에 미치는 후코이단의 효과)

  • Tae Hyun Kim;Jae Suk Woo
    • Journal of Life Science
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    • v.34 no.10
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    • pp.701-712
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    • 2024
  • Fucoidan is a polysaccharide found in brown algae, which is known for its various bioactive effects, including immune enhancement, anti-cancer, and anti-inflammatory properties. In this study, the effects of fucoidan on cellular and mitochondrial damage, as well as changes in osteogenic and osteoclastic activities induced by advanced glycation end-products (AGEs) in MC3T3-E1 osteoblast-like cells, were investigated. Treatment with AGEs resulted in a time- and dose-dependent decrease in MTT reduction capacity, activation of caspases (-3, -8, and -9), and an increase in apoptosis. Pre-treatment with fucoidan significantly alleviated these cellular damage markers caused by AGEs. In addition, fucoidan protected against AGEs-induced mitochondrial dysfunction by significantly mitigating the loss of mitochondrial membrane potential, reduction in intracellular ATP levels, and occurrence of mitochondrial permeability transition in AGEs-treated cells. Fucoidan also markedly suppressed the production of reactive oxygen species and, lipid and protein peroxidation induced by AGEs. In cells exposed to AGEs, gene expression related to osteogenic differentiation and markers of osteogenic activity increased, while markers of osteoclastic activity decreased. Fucoidan significantly moderated these changes. In conclusion, AGEs induce mitochondrial dysfunction and apoptosis in MC3T3-E1 cells, while decreasing osteogenic differentiation and activity, and increasing osteoclastic activity. Fucoidan appears to reduce cellular and mitochondrial damage and improve osteogenic activity impaired by AGEs.

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.

Inhibitory Effects of the EtOH Extract of Aster koraiensis on AGEs formation in STZ-induced diabetic rats and AGEs-induced Protein Cross-linking in vitro (벌개미취 에탄올추출물의 STZ-유도 당뇨 모델에서의 최종당화산물의 생성 및 교차결합에 미치는 효과)

  • Kim, Junghyun;Kim, Chan-Sik;Kim, Jin Sook
    • Korean Journal of Pharmacognosy
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    • v.47 no.4
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    • pp.312-318
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    • 2016
  • Advanced glycation end products (AGEs) such as $N^{\varepsilon}$-(carboxy-methyl)lysine (CML) have been implicated in the development of diabetic nephropathy. The aim of this study was to investigate the inhibitory effects of ethanolic extract of Aster koraiensis (AKE) on AGEs formation and AGEs-collagen cross-linking in vitro and CMLs formation in streptozotocin (STZ)-induced diabetic rats. AKE significantly inhibited AGEs formation ($IC_{50}$ value of $18.74{\mu}g/mL$) and AGEs-collagen cross-linking ($IC_{50}$ value of 0.274 mg/mL) in vitro than the well-known glycation inhibitor aminoguanidine ($IC_{50}$ value of $72.12{\mu}g/mL$ and 1.99 mg/mL, respectively). AKE (100 mg/kg per day) was given to diabetic rats for 9 weeks. In STZ-induced diabetic rats, severe hyperglycemia was developed, and urinary CMLs and plasma CMLs were markedly increased. Immunohistochemical stain revealed that CMLs were accumulated within renal glomerulus in STZ-induced diabetic rats. However, AKE significantly reduced urinary CMLs and plasma CMLs in diabetic rats. CMLs accumulation was inhibited by AKE treatment in the renal glomerulus. These results suggest that AKE had an inhibitory effect of AGE accumulation in the glomeruli of diabetic rat and could be an inhibitor of AGE-induced protein cross-linking. The oral administration of AKE may significantly help to prevent the progression of diabetic nephropathy in patients with diabetes.

Gold Nanoparticles Inhibit AGEs Induced Migration and Invasion in Bovine Retinal Endothelial Cells (소망막내피세포에서 금 나노입자의 최종당화산물에 의한 세포 이동 및 침윤성 억제 효과)

  • Chae, Soo-Chul
    • Korean Journal of Environmental Biology
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    • v.28 no.1
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    • pp.8-13
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    • 2010
  • This study aimed the role of gold nanoparticles (AuNP) in advanced glycation end-products (AGEs) induced migration and invasion in bovine retinal endothelial cells (BRECs). BRECs were isolated from the retina. Cell viability was confirmed by the MTT assay. In vitro wound migration assay was performed to investigate the migration of BRECs. In vitro tube formation was measured by on-gel system. Apoptosis induced by AuNP was confirmed by caspase-3 assay. AGE-bovine serum albumin (BSA) demonstrated increase of cell migration and proliferation in BRECs. In addition, AuNP regardless of the existence of AGE-BSA suppressed proliferation, migration, and angiogenesis. AuNP suppressed AGE-BSA induced migration and invasion, and induced apoptosis through caspase-3. As a results, AuNP have a potential anti-angiogenic effect for AGE-induced angiogenesis in vitro and offer possibility for the treatment of diabetic retinopathy.

Beneficial Effect of Lespedeza cuneata (G. Don) Water Extract on Streptozotocin-induced Type 1 Diabetes and Cytokine-induced Beta-cell Damage

  • Kim, Min Suk;Sharma, Bhesh Raj;Rhyu, Dong Young
    • Natural Product Sciences
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    • v.22 no.3
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    • pp.175-179
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    • 2016
  • The aim of this study was to evaluate the anti-diabetic effects of the water extract of Lespedeza cuneata (LCW) using rat insulinoma (RIN) m5F cells and streptozotocin (STZ)-induced diabetic rats. The effect of LCW on the protection of pancreatic beta cells was assessed using MTT assay, and nitric oxide production was assessed using Griess reagent. STZ-induced diabetic rats were treated with 100 and 400 mg/kg body weight of LCW for 5 weeks. In results, LCW significantly protected cytokine-induced toxicity and NO production, and increased insulin secretion in RINm5F cells. LCW significantly decreased serum blood glucose, thiobarbituric acid reactive substances (TBARS), blood urea nitrogen (BUN) and advanced glycation end products (AGEs) levels, and renal fibronectin expression in STZ-induced diabetic rats. Also, LCW effectively improved BW loss in STZ-induced diabetic rats. Thus, our results suggest that LCW has a beneficial effect on cytokine-induced pancreatic beta cell damage and biomarkers of diabetic complication in hyperglycemic rats.

Hypericin, a Naphthodianthrone Derivative, Prevents Methylglyoxal-Induced Human Endothelial Cell Dysfunction

  • Do, Moon Ho;Kim, Sun Yeou
    • Biomolecules & Therapeutics
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    • v.25 no.2
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    • pp.158-164
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    • 2017
  • Methylglyoxal (MGO) is a highly reactive metabolite of glucose which is known to cause damage and induce apoptosis in endothelial cells. Endothelial cell damage is implicated in the progression of diabetes-associated complications and atherosclerosis. Hypericin, a naphthodianthrone isolated from Hypericum perforatum L. (St. John's Wort), is a potent and selective inhibitor of protein kinase C and is reported to reduce neuropathic pain. In this work, we investigated the protective effect of hypericin on MGO-induced apoptosis in human umbilical vein endothelial cells (HUVECs). Hypericin showed significant anti-apoptotic activity in MGO-treated HUVECs. Pretreatment with hypericin significantly inhibited MGO-induced changes in cell morphology, cell death, and production of intracellular reactive oxygen species. Hypericin prevented MGO-induced apoptosis in HUVECs by increasing Bcl-2 expression and decreasing Bax expression. MGO was found to activate mitogen-activated protein kinases (MAPKs). Pretreatment with hypericin strongly inhibited the activation of MAPKs, including P38, JNK, and ERK1/2. Interestingly, hypericin also inhibited the formation of AGEs. These findings suggest that hypericin may be an effective regulator of MGO-induced apoptosis. In conclusion, hypericin downregulated the formation of AGEs and ameliorated MGO-induced dysfunction in human endothelial cells.

In vivo Screening of Herbal Extracts on High Glucose-induced Changes in Hyaloid-Retinal Vessels of Zebrafish (고혈당으로 유도된 제브라피쉬 당뇨망막병증 모델에서 약용식물의 효능 평가)

  • Lee, Yu-Ri;Jung, Seung-Hyun;Lee, Ik Soo;Kim, Joo Hwan;Kim, Young Sook;Kim, Jin Sook
    • Korean Journal of Pharmacognosy
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    • v.50 no.1
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    • pp.25-31
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    • 2019
  • The zebrafish (Danio rerio) is an established model organism for several pathophysiological conditions which are related to human diseases. In this study, we tested the preventive effect of eight herbal extracts, which show the inhibitory effect of advanced glycation end products (AGEs) or aldose reductase (AR) in our previous study, on high glucose (HG)-induced retinal vessel dilation in larval zebrafish and analyzed the change of hyaloid vasculature. HG-induced zebrafish hyaloid vasculatures were significantly increased in the thickness compared to untreated zebrafish (P<0.001, n=6~10). Eight herbal extracts were found to have significant retinal vessel dilation on the inhibitory activity. Particularly, Brandisia hancei (twigs and fruits), Castanopsis orthacantha (leaves and twigs), Litsea japonica (leaves and twigs), Spenceria ramalana (whole plant), and Synedrella nodiflora (leaves and stems) showed potent inhibitory activity against retinal vessel dilation in HG-induced larval zebrafish.

Glyoxalase 1 as a Therapeutic Target in Cancer and Cancer Stem Cells

  • Ji-Young, Kim;Ji-Hye, Jung;Seung-Joon, Lee;Seon-Sook, Han;Seok-Ho, Hong
    • Molecules and Cells
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    • v.45 no.12
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    • pp.869-876
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    • 2022
  • Methylglyoxal (MG) is a dicarbonyl compound formed in cells mainly by the spontaneous degradation of the triose phosphate intermediates of glycolysis. MG is a powerful precursor of advanced glycation end products, which lead to strong dicarbonyl and oxidative stress. Although divergent functions of MG have been observed depending on its concentration, MG is considered to be a potential antitumor factor due to its cytotoxic effects within the oncologic domain. MG detoxification is carried out by the glyoxalase system. Glyoxalase 1 (Glo1), the ubiquitous glutathionedependent enzyme responsible for MG degradation, is considered to be a tumor promoting factor due to it catalyzing the removal of cytotoxic MG. Indeed, various cancer types exhibit increased expression and activity of Glo1 that closely correlate with tumor cell growth and metastasis. Furthermore, mounting evidence suggests that Glo1 contributes to cancer stem cell survival. In this review, we discuss the role of Glo1 in the malignant progression of cancer and its possible use as a promising therapeutic target for tumor therapy. We also summarize therapeutic outcomes of Glo1 inhibitors as prospective treatments for the prevention of cancer.