• The Korean Journal of Physiology and Pharmacology
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• v.3 no.3
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• pp.251-261
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• 1999

The effects of carnosine and related compounds (CRCs) including anserine, homocarnosine, histidine, and ${\beta}-alanine$ on monosaccharide autoxidation and $H_2O_2$ formation were investigated. The incubation of CRCs with D-glucose, D-glucosamine, and D, L-glyceraldehyde at $37^{\circ}C$ increased the absorption maxima at 285 nm, 273 nm, and $290{\sim}330$ nm, respectively. D, L-glyceraldehyde was the most reactive sugar with CRCs. The presence of copper strongly stimulated the reaction of carnosine and anserine with D-glucose or D-glucosamine. Carnosine and anserine stimulated $H_2O_2$ formation from D-glucose autoxidation in a dose-dependent manner in the presence of 10 ${\mu}M$ Cu (II). The presence of human serum albumin (HSA) decreased their effect on $H_2O_2$ formation. Carnosine and anserine has a biphasic effect on ${\alpha}-ketoaldehyde$ formation from glucose autoxidation. CRCs inhibited glycation of HSA as determined by hydroxymethyl furfural, lysine residue with free ${\varepsilon}-amino$ group, and fructosamine assay. These results suggest that CRCs may be protective against diabetic complications by reacting with sugars and protecting glycation of protein.

• The Korea Journal of Herbology
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• v.32 no.3
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• pp.63-69
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• 2017

Objectives : Advanced glycation end product (AGEs) is combine formation of glucose and protein. AGEs and reactive oxygen species are potential therapeutic targets for the various disease such as diabetic complications, renal injury, skin damage. The aim of this study was investigated the AGEs inhibitory activity and antioxidant activity of water extracts from 40 Korean medicines and 5 heating-processed Korean medicines. Methods: AGEs formation inhibitory activities of Korean medicines measured using bovine serum albumin (BSA), glucose, and fructose. Then, five effective Korean medicines were selected and heated with 30% ethanol. The AGEs inhibitory activities of heated Korean medicine were measured compared with not-heated Korean medicines. The antioxidant activities 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. Furthermore, we examined total phenol and flavonoids contents. Results: Scutellariae Radix, Corni Fructus, Persimmon Fruit, Paeoniae Radix, Mori Folium respectively reduced AGEs production. Morever, heating-processed Scutellariae Radix has AGEs inhibitory activities better than not-processed Scutellariae Radix. Heating- processed Scutellariae Radix scavenged DPPH and ABTS effectively and $IC_{50}$ of DPPH and ABTS radical scavenging activity of Heat processed Scutellariae Radix were $15.47{\pm}0.26{\mu}g/m{\ell}$ and $12.07{\pm}1.23{\mu}g/m{\ell}$. It caused heat processing methods of Scutellariae Radix up regulated total phenol and flavonoids contents ($26.68{\pm}0.01$ to $46.15{\pm}0.10$, $20.30{\pm}0.38$ to $64.20{\pm}0.52$). Conclusion: It has AGEs inhibitory activities that 20 kind of medicinal plants of 40 medicinal plants. Especially, heat processed Scutellariae Radix has excellent AGEs inhibitory activities and antioxidant effect.

• Proceedings of the Korean Biophysical Society Conference
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• 1996.07a
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• pp.46-46
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• 1996

To elucidate the mechanism for the cross-linking reaction in the glycation or Maillard reaction, we studied the reaction between proteins, and a three-carbon ${\alpha}$-ketoaldehyde, methylglyoxal. When Cu, Zn-SOD was incubated with 200 mM of methylglyoxal, the peroxidase activity as well as the superoxide dismutase activity was reduced. This reduction is accompanied by the decrease of the anion binding affinity of the enzyme. (omitted)

• Interdisciplinary Bio Central
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• v.4 no.4
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• pp.13.1-13.6
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• 2012

The advanced glycation endproducts receptor (AGER) is a multiligand signal transduction receptor. One of its ligands, S100b molecules activates vascular smooth muscle cells and endothelial cells via its receptor, thus triggering activation of signaling cascades and generation of cytokines and proinflammatory molecules. Ubiquitin-conjugating enzyme Ubc9 is an E2 conjugating enzyme that transfers the activated small ubiquitin-related modifier to protein substrates, and thus it plays a critical role in SUR-Mylation-mediated cellular pathways. Previous studies have shown that both AGE-R and Ubc9 play roles in diverse cellular signaling pathways. However, until recently, little attention has been paid to interactions between AGE-R and Ubc9. In this study, sequence database searches allowed us to identify a potential interaction motif between AGE-R and Ubc9. The subsequent biochemical and molecular biological analysis suggested that there may be specificity in AGE-R and Ubc9 complex signaling in atherosclerosis and cancer cells in a cell-type specific manner. Although the determinant for specificity in AGE-R and Ubc9 complex signaling in cancer cells and atherosclerosis is yet to be determined, this study provides the basis to develop a specific therapeutic application of AGE-R, SURM (small ubiquitin-related modifier)-1, and Ubc9 complex activation pathways in atherosclerosis, diabetes, cancer and inflammatory diseases.

• Natural Product Sciences
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• v.12 no.4
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• pp.210-213
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• 2006

A 4,5-dioxoaporphine type alkaloid, cepharadione B (1), a phenolic acid, protocatechuic acid (2), and flavonols, quercetin (3), afzelin (4), and quercitrin (5), were isolated from the EtOAc-soluble extract of the whole plants of Houttuynia cordata. All the isolates (1-5) were subjected to in vitro bioassays to evaluate advanced glycation end products (AGEs) formation and rat lens aldose reductase (RLAR) inhibitory activity. The three flavonols 3-5 exhibited a significant inhibitory activity on AGEs formation with $IC_{50}$ values of 66.9, 58.9, and $32.3{\mu}M$, respectively. While the two flavonol rhamnosides 4 and 5 showed a remarkable inhibitory activity against RLAR with $IC_{50}$ values of 0.81 and $0.16{\mu}M$, respectively.

• BMB Reports
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• v.41 no.7
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• pp.516-522
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• 2008

The glycation of BSA leads to protein/peptide modifications that result in the formation of AGEs. AGEs react with the amino groups of N-terminal amino acid residues, particularly arginine and lysine residues. Enhanced AGE formation exists in the blood and tissues of diabetics, as well as in aging and other disorders. The Identification of AGEs is of great importance. Mass spectrometry has been applied to identify and structurally elucidate AGEs. Here, we report on the identification of AGE-peptides and AGE precursors based on relative mass changes as a result of specific AGE formation. HPLC-ESIMS, ESI-MS/MS, and the Mascot database were used. The relative mass changes due to the specific type of AGE formation were added to the identified peptides followed by a manual search of the glycated samples, which resulted in the identification of seven peptides for the formation of five AGEs, namely CML, pyrraline, imidazolone A, imidazolone B, and AFGP. Four glycated peptides (FPK, ECCDKPLLEK, IETMR, and HLVDEPQNLIK) were identified in the formation of AGE-precursors.

• Natural Product Sciences
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• v.13 no.2
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• pp.160-163
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• 2007

Four glycosides, rosamultin (1), tetracentronside B (2), 4-O-methylellagic acid 3-O-${\alpha}$-$_L$-rhamnopyranoside (3), and vanillic acid 4-O-${\beta}$-$_L$-glucopyranoside (4), isolated from the roots extract of Potentilla discolor, were subjected to in vitro bioassays to evaluate the inhibitory activity on advanced glycation end products (AGEs) formation and rat lens aldose reductase (RLAR). Compound 3 exhibited a significant inhibitory activity against both AGEs formation and RLAR with IC$_{50}$ values of 79.5 and 8.03 ${\mu}$M, respectively. All the compounds (1-4) were isolated for the first time from this plant.

• 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.

• The Journal of Korean Medicine
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• v.29 no.4
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• pp.133-145
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• 2008

Objectives: The aim of present study was to investigate recovery effects of Hirudo, which has been used clinically in diabetes therapy. Methods: We established three groups: normal, control, Hirudo, and assigned 6 rats to each group. The normal group was not treated by any process and fed by normal saline. The control & Hirudo groups were administered streptozotocin (STZ) to induce diabetes. Hirudo extract was orally administered to the Hirudo group for 10 days. After 8 weeks, the rats were sacrificed and their body weight, 24hrs urinary protein excretion, glucose, albumin, BUN, creatinine, total-cholesterol, LDL-cholesterol, triglyceride in blood, and level of glycation end-product (AGE) and transforming growth factor (TGF-${\beta}1$) in serum were measured. Morphological profiles and morphometric studies of the kidney cortex, renal transforming growth factor (TGF-${\beta}1$) expression, and renal receptor for advanced glycation end-products (RAGE) expression were studied. Results: The following results were obtained. The protein amount in urine per 24hrs of the Hirudo-treated group as compared to the control group was significantly reduced. The BUN and creatinine level in serum of the Hirudo-treated group as compared to the control group was significantly inhibited. The construction change in kidney of the Hirudo-treated group as compared to the control group was significantly inhibited. The factor of the Hirudo-treated group as compared to the control group was significantly inhibited, which induced the construction change in kidney. Conclusions: The above results suggest that Hirudo partially improved the function of the kidney.

• Korean Journal of Pharmacognosy
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• v.39 no.3
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• pp.249-254
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• 2008

An 80% EtOH extract and the solvent fractions of the seeds of Cornus officinalis were evaluated for their inhibitory activities against advanced glycation end products (AGEs) formation and AGEs-induced protein cross-linking in vitro. In vitro assay for AGEs-bovine serum albumin (BSA) formation showed that the 80% EtOH extract, n-hexane, EtOAc, n-BuOH and water fractions significantly inhibited AGEs formation with observed $IC_{50}$ values of 1.13, 17.64, 1.52, 1.24 and $3.27{\mu}g/ml$, respectively. In indirect AGEs-ELISA assay, the 800% EtOH extract, EtOAc and n-BuOH fractions exhibited more potent inhibitory activity on AGEs-BSA formation than aminoguanidine, a well know AGEs inhibitor. Furthermore, the 80% EtOH extract and all the solvent fractions inhibited concentration-dependently AGE-BSA cross-linking to collagen. The 80% EtOH extract, EtOAc, n-BuOH and water fractions also had a breaking activity against preformed AGE-BSA cross-linking concentration dependently. Thus these results suggest that the 80% EtOH extract and fractions of the seeds of C. officinalis could be an inhibitor as well as breaker of AGE-BSA cross-linking.