Isoflavonoids from the Rhizomes of Belamcanda chinensis and Their Effects on Aldose Reductase and Sorbitol Accumulation in Streptozotocin Induced Diabetic Rat Tissues

Jung, Sang-Hoon,Lee, Yeon-Sil,Lee, Sanghyun,Lim, Soon-Sung,Kim, Yeong-Shik,Shin, Kuk-Hyun The Pharmaceutical Society of Korea 2002 Archives of Pharmacal Research Vol.25 No.3

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.

Isoflavonoids from the Rhizomes of Belamcanda chinensis and Their Effects on Aldose Reductase and Sorbitol Accumulation in Streptozotocin Induced Diabetic Rat Tissues

정상훈,이연실,이상현,임순성,김영식,신국현 대한약학회 2002 Archives of Pharmacal Research Vol.25 No.3

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 IC50 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.

Aldose Reductase: a cause and a potential target for the treatment of diabetic complications

Sapna Thakur,Sonu Kumar Gupta,Villayat Ali,Priyanka Singh,Malkhey Verma 대한약학회 2021 Archives of Pharmacal Research Vol.44 No.7

Diabetes mellitus, a disorder of metabolism,results in the elevation of glucose level in the blood. In thishyperglycaemic condition, aldose reductase overexpressesand leads to further complications of diabetes through thepolyol pathway. Glucose metabolism-related disorders arethe accumulation of sorbitol, overproduction of NADH andfructose, reduction in NAD + , and excessive NADPH usage,leading to diabetic pathogenesis and its complications suchas retinopathy, neuropathy, and nephropathy. Accumulationof sorbitol results in the alteration of osmotic pressureand leads to osmotic stress. The overproduction of NADHcauses an increase in reactive oxygen species productionwhich leads to oxidative stress. The overproduction of fructosecauses cell death and non-alcoholic fatty liver disease. Apart from these disorders, many other complications havealso been discussed in the literature. Therefore, the articleoverviews the aldose reductase as the causative agent and apotential target for the treatment of diabetic complications. So, aldose reductase inhibitors have gained much importanceworldwide right now. Several inhibitors, like derivativesof carboxylic acid, spirohydantoin, phenolic derivatives,etc. could prevent diabetic complications are discussedin this article.

수종 생약에 의한 Lens Aldose Reductase의 억제

정도래,박웅양,이승호,이경순,노재섭,Jeong, Do-Rae,Park, Woong-Yang,Lee, Seung-Ho,Lee, Kyong-Soon,Ro, Jai-Seup 한국생약학회 1993 생약학회지 Vol.24 No.1

To search for inhibitory activities for lens aldose reductase, twenty two medicinal plants were tested by the method of bovine lens aldose reductase inhibition test. In this test Rubia akane(68%), Artemisia selengensis(61%), Lespedeza cuneata (58%), Ligustrum lucidum(58%), Viola patrinii(58%) extracts were shown to have aldose reductase inhibitory activity. From the radix of Rubia akane, $2-methyl-1,\;3,\;6-trihydroxy-9,\;10-anthraquinone-3-O-(6'-O-acetyl)-{\alpha}-rhamnosyl-(1{\rightarrow}2)-{\beta}-D-glucoside$ was isolated and the $IC_{50}$ of this compound in the aldose reductase inhibition test was about $1.2{\times}10^{-6}M$.

흑삼릉의 수치에 따른 Aldose Reductase 및 항산화활성에 미치는 영향

정상훈,신국현,신현경,임순성 대한약학회 2004 약학회지 Vol.48 No.5

Sparganium stoloniferum Buch.-Ham. (Sparganiaceae) is a perennial herb which has been used as treatments for menstrual disorder, galactagogue and endometriosis in folk remedies. The Sparganii Rhizoma processed, heated with vinegar, used to different purpose compared with origin in medicine. In order to estimate the different effects between processed (PSR) and unprocessed (USR) Sparganii Rhizoma, extraction and systemic fractionation of the rhizomes were archived. Inhibitory effects of the extracts as well as the fractions of PSR and USR on rat lens aldose reductase and on rat platelet aggregation were investigated for the prevention or the treatment of chronic diabetic complications. Their antioxidant effects, measured using lipid peroxidation of liver tissue and radical scavenging activities on 1,1-diphenyl-picrylhydrazyl in vitro, were evaluated. The most of biological activities tested except rat platelet aggregation, fractions from PSR were shown to exhibit stronger activities than those from USR. It seems that caused by changing of the chemical components by heating process in conditioned with acetic acid. Compounds isolated were shown to significant inhibitory activity on rat lens aldose reductase. Inhibitory activity of compounds isolated on rat lens aldose reductase have been tested in vitro. $IC_{50}$/ (6.31 $\mu$M) of cerebroside I (V) was nearly equal to that (6.32 $\mu$M) of a reference compound, tetrametbylene glutaric acid (TMG).

Aldose Reductase Inhibitors from the Leaves of Salix hulteni

Hyun Young Park,김명조,Hye Kyung Kim,Seong Ho Jeon,Soo Hee Kim,전완주,임순성,권용수 한국응용생명화학회 2009 Applied Biological Chemistry (Appl Biol Chem) Vol.52 No.5

From the n-BuOH soluble fraction of the leaves of Salix hulteni, six compounds were isolated as aldose reductase inhibitors. On the basis of spectral data, these compounds were identified as diosmetin-7-O-β-D-glucoside (1), isoquercitrin (2), diosmetin-7-O-β-D-xylosyl-(1→6)-β-D-glucoside (3), aromadendrin-3-O-β-D-glucoside (4), astragalin (5), and p-hydroxyacetophenone glucoside (6). All of the isolates were evaluated in vitro for inhibitory activity against the aldose reductase. Of these, compounds 1-5 exhibited inhibitory activity against aldose reductase with IC50 values ranging 1.4 to 5.8 µM.

한국산 한약재 (생약) 추출물의 알도즈 환원 효소 억제 효능 검색과 꽃개오동의 수정체 혼탁 억제 (I)

이윤미,김란희,김영숙,장대식,김주환,배기환,김진숙,김종민 한국생약학회 2008 생약학회지 Vol.39 No.3

Aldose reductase (AR), the principal enzyme of the polyol pathway, has been shown to play an important role inthe diabetic complications, including diabetic cataract. The inhibitors of AR, therefore, would be potential agents for preventionof diabetic complications. As part of our ongoing project directed toward the discovery of preventive and/or treatment for diabeticcomplications, 48 Korean herbal medicines have been investigated with an in vitro evaluation system using aldose reductaseinhibitory activities. Of these, 12 herbal medicines exhibited a significant inhibitory activity against aldose reductase. Particularly, seven herbal medicines, i.e., Eurya japonica, Chrysanthemum indicum, Akebia quinata, Saururus chinensis, Catalpabignonioides, Lonicera japonica, Vitex rotundifolia showed two times more potent inhibitory activity than the positive control3.3-tetramethyleneglutaric acid (TMG). In addition, Catalpa bignonioides showed the retardation of cataract-opacificationof the lens of the eye under diabetic condition by xylose. Therefore, this result may provide a potential therapeutic approachfor preventing and treating diabetic cataracts.

베트남 약용식물 추출물의 알도즈 환원 효소 억제 효능 검색(II)

이윤미,김영숙,장대식,김종민,배기환,김주환,김진숙 한국생약학회 2008 생약학회지 Vol.39 No.4

Aldose reductase (AR), the key enzyme in the polyol pathway, plays an important role in the pathogenesis of diabeticcomplications 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 diabeticcomplications. 49 Vietnam herbal medicines have been investigated with an in vitro evaluation system using aldose reductaseinhibitory activities. Of these, 7 herbal medicines, Artemisia annua (leaf, stem), Duranta repens (leaf, stem), Excoecariacochinchinensis (aerial part), Flueggea virosa (leaf, stem), Khaya senegalensis (leaf), Polygonum orientale (aerial part), Toxicodendronsuccedanea (leaf, stem) exhibited a significant inhibitory activity against aldose reductase. Particularly, Durantarepens (leaf, stem) and Toxicodendron succedanea (leaf, stem) showed two times more potent inhibitory activity than the positivecontrol, 3.3-tetramethyleneglutaric acid (TMG).

Aldose Reductase Inhibitors from the Leaves of Salix hulteni

Park, Hyun-Young,Kim, Hye-Kyung,Jeon, Seong-Ho,Kim, Soo-Hee,Chun, Wan-Joo,Lim, Soon-Sung,Kim, Myong-Jo,Kwon, Yong-Soo The Korean Society for Applied Biological Chemistr 2009 Applied Biological Chemistry (Appl Biol Chem) Vol.52 No.5

From the n-BuOH soluble fraction of the leaves of Salix hulteni, six compounds were isolated as aldose reductase inhibitors. On the basis of spectral data, these compounds were identified as diosmetin-7-O-${\beta}$-D-glucoside (1), isoquercitrin (2), diosmetin-7-O-${\beta}$-D-xylosyl-(1${\rightarrow}$6)-${\beta}$-D-glucoside (3), aromadendrin-3-O-${\beta}$-D-glucoside (4), astragalin (5), and p-hydroxyacetophenone glucoside (6). All of the isolates were evaluated in vitro for inhibitory activity against the aldose reductase. Of these, compounds 1-5 exhibited inhibitory activity against aldose reductase with $IC_{50}$ values ranging 1.4 to 5.8 ${\mu}M$.

Rats Lens Aldose Reductase Inhibitor Activities of Leguminous Seed Extracts

Kim, Byung-Su,Kim, Min-Jeong,Kim, Hye-Young,Ahn, Young-Joon,Lee, Hoi-Seon The Korean Society of Food Science and Nutrition 2001 Preventive Nutrition and Food Science Vol.6 No.1

The methanol extracts of 25 leguminous seeds in vitro were evaluated for inhibitory activities against lens aldose reductase of Sprague Dawley male rats. The responses varied with both leguminous seed and concentration used. At the concentration of 0.1 mg/mL, the methanol extracts from Amphicaraea edgeworthii, Canavalia lineata, Gylcine max var. solitae, Glycine max var. yagkong, Glycine max var. hooktae, Glycine max var. bangkong, Glycine max var. geumdu, Glycine max var. chungtae, Glycine max var. mejukong, Glycine soja, Phaseolus radiatus var. geodu, Vicia tetrasperma, Vigna angulasis, and Vigna sinensis inhibited enzyme activity by greatertha 60%. In following study, at the concentration of 0.01 mg/mL, the extracts of C. lineata and V. tetraspermahad relatively strong inhibitory activity against aldose reductase. Because of their potent inhibitory activities, the activity of each solvent fraction from C. lineata and V. tetrasperma was determined, and the potent activity was showed from chloroform and hexane fractions, respectively. {TEX}$IC_{50}${/TEX} values of C. lineata and V. tetrasperma were 0.004 and 0.006 mg/mL, respectively. As a naturally occurring therapeutic agent, leguminous seeds described could be useful for developing new agents of antidiabetic complications.