• 생약학회지
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• 제45권4호
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• pp.359-365
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• 2014

Aldose reductase (AR) is the key enzyme of the polyol pathway in the development of the diabetic complications. Sixty seven Chinese herbal medicines have been investigated for inhibitory activities on AR. Among them, 7 herbal medicines, Buddleja crispa (twigs and leaves), Taiwania flousiana (twigs and leaves), Sloanea hemsleyana (fruits), Euphorbia nemetocypha (whole plants), Photinia glomerata (twigs and leaves), Vitex yunnanensis (twigs and leaves) exhibited a significant inhibitory activity against AR. Particularly, S. hemsleyana and V. yunnanensis showed 1.2-4.5 times more potent inhibitory activity than the positive control, 3,3-tetramethyleneglutaric acid (TMG).

• 생약학회지
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• 제45권4호
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• pp.366-375
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• 2014

Aldose reductase (AR) has been indicated the critical enzyme of the polyol pathway in the development of the diabetic complications. In this study, 119 Vietnamese herbal medicines have been investigated for inhibitory activities on AR. Among them, 7 herbal medicines, Synedrella nodiflora (stems and leaves), Combretum sundaicum (stems and leaves), Argyreia acuta (stems and leaves), Platea latifolia (whole plants), Linociera sangda (whole plants), Rhaphiolepis indica (whole plants), Harrisonia perforata (stems and leaves) and 2 fractions from Harrisonia perforata (stems and leaves) with EtOAc and BuOH, exhibited a significant inhibitory activity against AR. Particularly, S. nodiflora, A. acuta and H. perforata (stems and leaves) showed 1.0-1.8 times more potent inhibitory activity than the positive control, 3,3-tetramethyleneglutaric acid (TMG).

• Natural Product Sciences
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• 제10권1호
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• pp.35-39
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• 2004

Aldose reductase (AR), the key enzyme of the polyol pathway, is known to play important roles in the diabetic complications. The inhibitors of AR, therefore, would be potential agents for the prevention of diabetic complications. In order to clarify the structural requirements of flavonoids for aldose reductase inhibitory activity, thirty flavonoids were examined. Among the thirty flavonoids, flavonols such as quercetin (5), reyneutrin (7), quercitrin (9), isoquercitrin (11), and avicularin (14) were found to exhibit much stronger AR inhibition. Lonicerin (10), amentoflavone (27) and sophoraflavanone B (30) were also showed strong inhibitory activity. Especially, quercitrin and reyneutrin exhibited the most inhibitory potency on rat lens (RL) AR. The results suggested that flavonol having the 7-hydroxyl and/or catechol moiety at the B ring exhibit strong activity. In addition, flavonols having 3-O-monosaccharide also showed stronger inhibition than free flavonols at the 3-position. These results suggested that quercitrin and reyneutrin are attributed to be the promising compounds for the prevention and/or treatment of diabetic complications.

• Archives of Pharmacal Research
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• 제25권3호
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• pp.306-312
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• 2002

Aldose reductase, the key enzyme of the polyol pathway, is known to play important roles in the diabetic complication. The inhibitors of aldose reductase, therefore, would be potential agents for the prevention of diabetic complications. To evaluate active principles for the inhibition of aldose reductase from the rhizomes of Belamcanda chinensis, twelve phenolic compounds were isolated and tested for their effects on rat lens aldose reductase. As a result, isoflavones such as tectorigenin, irigenin and their glucosides were found to show a strong aldose reductase inhibition. Tectoridin and tectorigenin, exhibited the highest aldose reductase inhibitory potency, their $IC_{50}$ values, being $1.08{\times}10^{-6}{\;}M{\;}and{\;}1.12{\times}10^{-6}{\;}M$, respectively, for DL-glyceraldehyde as a substrate. Both compounds, when administered orally at 100 mg/kg for 10 consecutive days to streptozotocin-induced diabetic rats, caused a significant inhibition of sorbitol accumulation in the tissues such as lens, sciatic nerves and red blood cells. Tectorigenin showed a stronger inhibitory activity than tectoridin. From these results, it is suggested that tectorigenin is attributed to be a promising compound for the prevention and/or treatment of diabetic complications.

• 생약학회지
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• 제42권2호
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• pp.187-194
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• 2011

Aldose reductase (AR), the key enzyme in the polyol pathway, plays an important role in the development of the diabetic complications. None of Aldose reductase Inhibitor (ARI) has achieved worldwide use because of limited efficacy or undesirable side effects. Therefore, evaluating natural sources for ARI potential may lead to the development of safer and more effective agents against diabetic complications. Fifty two Chinese herbal medicines have been investigated for inhibitory activities on AR. Among them, twelve herbal medicines, Artemisia anomala (aerial part), Centella asiatica (aerial part), Scutellaria baicalensis (root), Senecio chrysanthermoides (whole plant), Gleditsia japonica (twig), Zizyphus jujube (twig, leaf), Citrus aurantium (fruit), Hydnocarpus anthelmintica (fruit), Potaninia mongolica (aerial part), Tribulus terrestris (fruit), Artemisia apiacea (aerial part) and Eclipta prostrate (aerial part) exhibited a significant inhibitory activity against AR. Particularly, Artemisia anomala, Centella asiatica and Scutellaria baicalensis showed four times more potent inhibitory activity than the positive control, 3,3-tetramethyleneglutaric acid (TMG).

• Journal of Yeungnam Medical Science
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• 제40권4호
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• pp.328-334
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• 2023

An aging population and changes in dietary habits have increased the incidence of diabetes, resulting in complications such as diabetic foot ulcers (DFUs). DFUs can lead to serious disabilities, substantial reductions in patient quality of life, and high financial costs for society. By understanding the etiology and pathophysiology of DFUs, their occurrence can be prevented and managed more effectively. The pathophysiology of DFUs involves metabolic dysfunction, diabetic immunopathy, diabetic neuropathy, and angiopathy. The processes by which hyperglycemia causes peripheral nerve damage are related to adenosine triphosphate deficiency, the polyol pathway, oxidative stress, protein kinase C activity, and proinflammatory processes. In the context of hyperglycemia, the suppression of endothelial nitric oxide production leads to microcirculation atherosclerosis, heightened inflammation, and abnormal intimal growth. Diabetic neuropathy involves sensory, motor, and autonomic neuropathies. The interaction between these neuropathies forms a callus that leads to subcutaneous hemorrhage and skin ulcers. Hyperglycemia causes peripheral vascular changes that result in endothelial cell dysfunction and decreased vasodilator secretion, leading to ischemia. The interplay among these four preceding pathophysiological factors fosters the development and progression of infections in individuals with diabetes. Charcot neuroarthropathy is a chronic and progressive degenerative arthropathy characterized by heightened blood flow, increased calcium dissolution, and repeated minor trauma to insensate joints. Directly and comprehensively addressing the pathogenesis of DFUs could pave the way for the development of innovative treatment approaches with the potential to avoid the most serious complications, including major amputations.

• 생약학회지
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• 제41권4호
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• pp.289-296
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• 2010

Aldose reductase (AR), the principal enzyme of the polyol pathway, has been shown to play an important role in the development of the diabetic complications. Evaluating natural sources for ARI potential may lead to the development of safer and more effective agents against diabetic complications. Sixty four Chinese herbal medicines have been investigated for inhibitory activities on AR. Among them, thirteen herbal medicines, Inula helianthus-aquatilis C. Y. Wu ex Ling. (whole plant), Erigeron breviscapus (Vant.) Hand. Mazz. (whole plant), Lonicera hypoglauca Miq. (leaf, stem), Scutellaria orthocalyx Hang. Mazz. (whole plant), Berchemia floribunda Brongn. (leaf, stem), Michelia alba DC. (flower), Oroxylum indicum (seed), Punica granatum L. (peel), Elsholtzia capituligera (whole plant), Trachelospermum jasminoides (Lindl.) Lem. (whole plant), Elsholtzia strobilifera Benth. (whole plant), Agrimonia pilosa var. nepalensis (D. Don) Nakai (whole plant) and Aster poliothamnus Diels (whole plant) exhibited a significant inhibitory activity against AR. Particularly, Inula helianthus-aquatilis C. Y. Wu ex Ling. showed seven times more potent inhibitory activity than the positive control, 3,3-tetramethyleneglutaric acid (TMG).

• 생약학회지
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• 제40권4호
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• pp.394-399
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• 2009

Aldose reductase (AR) is a critical enzyme in the development of the diabetic complications. AR, the first enzyme in the polyol pathway, catalyzes the reduction of the aldehyde form of glucose to sorbitol with concomitant conversion of NADPH to $NADP^+$. None of aldose reductase inhibitor (ARI) has achieved worldwide use because of limited efficacy or undesirable side effects. Therefore, evaluating natural sources for ARI potential may lead to the development of safer and more effective agents against diabetic complications. Forty eight Chinese herbal medicines have been investigated for inhibitory activities on AR. Among them, seven herbal medicines, Buddleja officinalis (whole plant), Lonicera japonica (leaf and flower), Polygonum aviculare (aerial part), Polygonum aviculare (whole plant), Salvia miltiorrhiza (root), Schisandra chinensis (stem), and Zanthoxylum armatum (leaf and stem) exhibited a significant inhibitory activity against AR. Particularly, L. japonica and P. aviculare showed two times more potent inhibitory activity than the positive control, 3,3-tetramethyleneglutaric acid (TMG).

• 생약학회지
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• 제39권4호
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• pp.324-329
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• 2008

Aldose reductase (AR), the key enzyme in the polyol pathway, plays an important role in the pathogenesis of diabetic complications such as cataract formation. AR inhibitors (ARI) can prevent or reverse early abnormalities in diabetic complications. However, none of ARI has achieved worldwide use because of limited efficacy or undesirable side effects. Therefore, evaluating natural sources for ARI potential may lead to the development of safer and more effective agents against diabetic complications. 49 Vietnam herbal medicines have been investigated with an in vitro evaluation system using aldose reductase inhibitory activities. Of these, 7 herbal medicines, Artemisia annua (leaf, stem), Duranta repens (leaf, stem), Excoecaria cochinchinensis (aerial part), Flueggea virosa (leaf, stem), Khaya senegalensis (leaf), Polygonum orientale (aerial part), Toxicodendron succedanea (leaf, stem) exhibited a significant inhibitory activity against aldose reductase. Particularly, Duranta repens (leaf, stem) and Toxicodendron succedanea (leaf, stem) showed two times more potent inhibitory activity than the positive control, 3.3-tetramethyleneglutaric acid (TMG).

• Journal of Microbiology and Biotechnology
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• 제30권2호
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• pp.271-278
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• 2020

Glycerol dehydrogenase (GlyDH) catalyzes the oxidation of glycerol to dihydroxyacetone (DHA), which is the first step in the glycerol metabolism pathway. GlyDH has attracted great interest for its potential industrial applications, since DHA is a precursor for the synthesis of many commercially valuable chemicals and various drugs. In this study, GlyDH from Klebsiella pneumoniae (KpGlyDH) was overexpressed in E. coli and purified to homogeneity for biochemical and molecular characterization. KpGlyDH exhibits an exclusive preference for NAD⁺ over NADP⁺. The enzymatic activity of KpGlyDH is maximal at pH 8.6 and pH 10.0. Of the three common polyol substrates, KpGlyDH showed the highest k_cat/K_m value for glycerol, which is three times higher than for racemic 2,3-butanediol and 32 times higher than for ethylene glycol. The k_cat value for glycerol oxidation is notably high at 87.1 ± 11.3 sec^-1. KpGlyDH was shown to exist in an equilibrium between two different oligomeric states, octamer and hexadecamer, by size-exclusion chromatography analysis. KpGlyDH is structurally thermostable, with a T_m of 83.4℃, in thermal denaturation experiment using circular dichroism spectroscopy. The biochemical and biophysical characteristics of KpGlyDH revealed in this study should provide the basis for future research on its glycerol metabolism and possible use in industrial applications.