Inhibition Of Rat Lens Aldose Reductase Research Articles

Plant-derived molecules from Saussurea grandifolia as inhibitors of aldose reductase

Saussurea grandifolia was tested for aldose reductase (AR) inhibition as part of a search for potentially therapeutic natural compounds. Stepwise polarity fractions were tested for in vitro inhibition of rat lens AR. Of these, the ethyl acetate (EtOAc) and n-butanol (n-BuOH) fractions exhibited AR inhibitory activities. A chromatographic separation of the active EtOAc and n-BuOH fractions led to the isolation of nine compounds, which were known and identified as vitexin (1), genkwanin-5-O-glucoside (2), vitexin 2″-p-hydroxybenzoate (3), kaempferol-3-O-rutinoside (4), isovitexin (5), quercitrin (6), isoquercitrin (7), 1,5-di-O-caffeoylquinic acid (8), and vicenin 1 (9). Among these compounds, compounds 6, 7, and 8 showed very strong inhibitory activities against AR (IC50’s = 0.34, 0.32, and 0.08 μM, respectively). The results suggest that S. grandifolia is clearly a potential source for therapeutic agent that might be useful for the treatment of diabetic complications.

Inhibitory efficacy of Ligularia fischeri against aldose reductase and advanced glycation end products formation

The efficacy of Ligularia fischeri (LF) for managing diabetic complications was evaluated by assessing inhibitory effects against advanced glycation end product (AGE) formation, rat lens aldose reductase (RLAR), and 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging. The ethyl acetate fraction from 70% ethanol extracts of LF showed the highest DPPH radical scavenging activity of 53.90% at a concentration of 3.3 μg/mL. The ethyl acetate fraction exhibited the most potent AGE formation inhibition of 73.57% at a concentration of 55 μg/mL and showed the most potent RLAR inhibition of 88.97% at a concentration of 11.11 μg/mL. The ethyl acetate fraction exhibited the most potent antioxidant and anti-diabetic effects. Nuclear magnetic resonance via bioactivity-guided fractionation of the LF ethyl acetate fraction revealed that 3,4-dicaffeoylquinic acid was the bioactive compound. This compound from LF can be effective for prevention or treatment of diabetic complications.

Screening of aldose reductase inhibitory activities of Korean folk plants in Chungcheong Province

To search for the aldose reductase (AR) inhibitors from Korean folk plants, the inhibition of rat lens AR in vitro using the methanol (MeOH) extracts from Korean folk plants in Chungcheong Province was investigated. Among Korean folk plants tested, the MeOH extract of Persicaria longiseta showed highest inhibition of AR (<TEX>$IC_{50}$</TEX> value, <TEX>$5.14{\mu}g/ml$</TEX>). Consequently, P. longiseta has a possibility of new natural resources for the development of AR inhibitor for the prevention of diabetic complications.

민속식물의 알도즈 환원효소 억제작용

Abstract : To search for the aldose reductase (AR) inhibitors from Korean folk plants, the inhibition of rat lens AR in vitro using the methanol (MeOH) extracts from Korean folk plants was investigated. Among fifty four Korean folk plants tested, the MeOH extract of Cedrela sinensis showed highest inhibition of AR (IC 50 value, 2.52 μg/ml). The plant C. sinensis has a possibility of new natural resources for the development of AR inhibitor for the prevention of diabetic complications. Key words : Aldose reductase inhibition, Cedrela sinensis , Diabetic complications, Folk plant *Corresponding author: Tel: +82-31-670-4688E-mail address: slee@cau.ac.kr I. Introduction Folk plants are traditional plants widely known among the people in daily life for food, disease remedy, and personal preference for a long time. The use of tradi-tional medicine has been expanded globally and gaining popularity during last decade. It has been estimated that about 20,000 plant species are used for medicinal purposes throughout the world. According to World Health Organization (WHO) report (2002), 70% of the world population use medicinal plants for curing diseases through their traditional practitioners. In sub-continent, plant oriented drugs are used extensively and from a very long time. According to a survey conducted by WHO, traditional healers treat 65% patients in Srilanka, 60% in Indonesia, 75% in Nepal, 85% in Myanmar, 80% in India, and 90% in Bangladesh. In Pakistan, 60% of the population, especially in villages is getting health care by traditional practitioners, who prescribe herbal preparations (Hamayun et al., 2006). Developed countries are turning to the use of traditional medicinal systems that involve the use of herbal drugs and remedies. About 1,400 herbal preparations are used widely, according to a recent survey in Member States of the European Union. Herbal preparations are popular and are of significance in primary healthcare in Belgium, France, Germany and the Netherlands. Such popularity of healthcare plant-derived products has been traced to their increasing acceptance and use in the cosmetic industry as well as to increasing public costs in the daily maintenance of personal health and well-being (Hoareau and da Silva, 1999). Like the preceding, herbal medicines for disease remedy are an important

화이트 칼라소재의 알도즈 환원효소 억제작용 탐색

The purpose of this study was to evaluate the potential of naturally occurring aldose reductase (AR) inhibitors from white-color natural products (Aruncus dioicus var. kamtschaticus, Chionanthus retusa, Cosmos bipinnatus, Hibiscus syriacus, Hydrangea paniculata, Magnolia denudata, Prunus padus, Robinia pseudo-accacia, Rhododendron mucronulatum for. albiflorum, Spiraea blumei, and Spiraea prunifolia var. simpliciflora). The MeOH extract of white-color natural products were tested on rat lens AR inhibition in vitro. Among them, the MeOH extract of R. mucronulatum for. albiflorum showed highest inhibition on AR (<TEX>$IC_{50}$</TEX> value, 1.07 <TEX>${\mu}g/ml$</TEX>). These results suggested that R. mucronulatum for. albiflorum, a white-color natural product, could be a useful resource in the development of a novel AR inhibitory agent against diabetic complications.

Inhibitory Activity of Caffeoylquinic Acids from the Aerial Parts of Artemisia princeps on Rat Lens Aldose Reductase and on the Formation of Advanced Glycation End Products

Caffeoylquinic acids -3,4-di-O-caffeoylquinic acid (1); 1,3,5-tri-O-caffeoylquinic acid (2); and 3,4,5-tri-O-caffeoylqunic acid (3)- were isolated from an acetone-soluble fraction of the aerial parts of Artemisia princes. Their structures were determined spectroscopically using 1D- and 2D-nuclear magnetic resonance (NMR) studies, as well as by comparing the NMR results with previously published structures. All the isolates were subjected to in vitro bioassays to evaluate their efficacy in inhibiting rat lens aldose reductase (RLAR) activity and the formation of advanced glycation end products (AGEs). We found 1,3,5-tri-O-caffeoylquinic acid (2) to be the most potent AGE inhibitor, and the concentration that resulted in 50% inhibition (IC50) was 22.18 ±1.46 mM, as compared to the aminoguanidine and chlorogenic acid controls, which had IC50 values of 1,093.11±10.95 and 117.63±0.20 mM, respectively. In the RLAR assay, the three caffeoylquinic acids were found to have IC50 values in the range of 1.78-2.40 μM, demonstrating a 5- to 10-fold greater efficacy in RLAR inhibition as compared to the quercetin control, which had an IC50 value of 17.91 μM.

Aldose Reductase Inhibitors fromViola hondoensisW. Becker et H Boss

The isolation and characterization of rat lens aldose reductase inhibitors from the Viola hondoensis W. Becker et H Boss were conducted. The extracts and organic fractions from V. hondoensis were tested. The MeOH extract and EtOAc fraction were found to exhibit potent rat lens aldose reductase inhibition in vitro, their IC(50) being 1.2 and 0.6 microg/ml, respectively. One major isoflavonoid glycoside was isolated from the ethyl acetate soluble fraction of V. hondoensis. Kakkalide was found to be the potential rat lens aldose reductase inhibitor (IC(50) = 0.34 microg/ml), and may be useful for the prevention and/or treatment of diabetic complications.

Constituents from the fruiting bodies ofGanoderma applanatum and their aldose reductase inhibitory activity

Eight compounds were isolated from the fruiting bodies of Ganoderma applanatum, and were identified as 2-methoxyfatty acids (1), 5-dihydroergosterol (2), ergosterol peroxide (3) 3beta,7beta, 20,23xi-tetrahydroxy-11,15-dioxolanosta-8-en-26-oic acid (4), 7beta,20,23xi-trihydroxy-3,11,15-trioxolanosta-8-en-26-oic acid (5), cerevisterol (6), 7beta,23xi-dihydroxy-3,11,15-trioxolanosta-8,20E (22)-dien-26-oic acid (7), and 7beta-hydroxy-3,11,15,23-tetraoxolanosta-8,20E(22)-dien-26-oic acid methyl ester (8) by spectral analysis. All compounds were isolated for the first time from this fruiting bodies, and their effect on rat lens aldose reductase (RLAR) activity was tested. Among these eight compounds, ergosterol peroxide (3) was found to exhibit potent RLAR inhibition, its IC50 value being 15.4 microg/mL.

Inhibitory Effects of Isorhamnetin-3-O-.BETA.-D-glucoside from Salicornia herbacea on Rat Lens Aldose Reductase and Sorbitol Accumulation in Streptozotocin-Induced Diabetic Rat Tissues

The inhibitory effects of compounds from Salicornia herbacea (Chenopodiaceae) on rat lens aldose reductase (RLAR) and sorbitol accumulation in streptozotocin-induced diabetic rat tissues were investigated. The various fractions from the MeOH extract of S. herbacea were tested for their effects on RLAR in vitro. Among them, the EtOAc fraction was found to exhibit a potent RLAR inhibition (IC(50)=0.75 microg/ml), from which an active principle as a potent AR inhibitor was isolated and its chemical structure was elucidated as isorhamnetin-3-O-beta-D-glucoside (1) by spectral analysis. Compound 1 exhibited a potent RLAR inhibition in vitro, its IC(50) being 1.4 microM. Compound 1, when administered orally at 25 mg/kg in streptozotocin (STZ)-induced diabetic rats, caused not only a significant inhibition of serum glucose concentration but also sorbitol accumulation in the lenses, red blood cells (RBC), and sciatic nerves. These results indicate that compound 1 from S. herbacea is a leading compound for further study as a new drug for the prevention and/or treatment of diabetes and its complications.

Aldose Reductase Inhibitors from the Fruiting Bodies of Ganoderma applanatum

The isolation and characterization of rat lens aldose reductase (RLAR) inhibitors from the fruiting bodies of Ganoderma applanatum were conducted. Among the extracts and fractions from G. applanatum tested, the MeOH extract and EtOAc fraction were found to exhibit potent RLAR inhibition in vitro, their IC50 being 1.7 and 0.8 microg/ml, respectively. From the active EtOAc fraction, seven compounds with diverse structural moieties were isolated and identified as D-mannitol (1), 2-methoxyfatty acids (2), cerebrosides (3), daucosterol (4), 2,5-dihydroxyacetophenone (5), 2,5-dihydroxybenzoic acid (6), and protocatechualdehyde (7). Among them, protocatechualdehyde (7) was found to be the most potent RLAR inhibitor (IC50=0.7 microg/ml), and may be useful for the prevention and/or treatment of diabetic complications.

한국산 해산식물의 추출물로부터 Aldose Reductase 억제활성의 검색

We examined MeOH extracts of the marine plants from Korea for their inhibitory activities on rat lens aldose reductase in vitro. Among the MeOH extracts tested, the extracts of Enteromorpha prolifera, Ecklonia cava, Pelvetia siliquosa and Salicornia herbacea exhibited a rat lens aldose reductase inhibition (IC: 3.04, 8.84, 11.42 and 4.99 g-ml, respectively) in vitro.

Screening of Korean forest plants for rat lens aldose reductase inhibition.

Naturally occurring substances which can prevent and treat diabetic complications were sought by examining ethanol extracts prepared from Korean forest plants for their inhibitory effects on rat lens aldose reductase activity in vitro. Among the plants examined, Acer ginnala, Illicium religiosum and Cornus macrophylla exerted the most strong inhibitory activity on aldose reductase.

Isolation of aldose reductase inhibitors from the flowers ofChrysanthemum boreale

The methanol extract from the whole parts of the flowers ofChrysanthemum boreale was found to exhibit a significant inhibition of rat lens aldose reductase (RLAR) activityin vitro. Bioassay guided systematic fractionation of the methanol extract led to the isolation of four flavonoids which were identified as acacetin (I), apigenin (II), luteolin (III) and linarin (IV). Compounds I–III were demonstrated to exhibit a significant inhibition of RLAR. Luteolin (III) was found to be the most potent AR inhibitor with IC50 value of 5×10−7M.

X-ray affinity and photoaffinity inhibitor of aldose reductase.

A reversible affinity inhibitor of rat lens aldose reductase (RLAR), that can be transformed into an irreversible inhibitor by low doses of X-rays or by exposure to light, has been synthesized and characterized. The inhibitor consists of quercitrin, a reversible receptor binding moiety, that is connected through a hexanediamine spacer to an azido containing moiety which becomes chemically reactive when irradiated. This reagent, N-(2-nitro-4-azidophenyl)-hexamethylenediamine-N'-(3'-O-quercit rin), (NAP-HEX-Q), represents a new class of affinity agents which have potential applications as target-entrapped drugs. The KI's for quercitrin and NAP-HEX-Q, both non-competitive inhibitors, are 0.6 uM and 0.5 uM, respectively. Rates are calculated from the tangent of the angle of descent of the linear absorbance vs time plots, measured simply and rapidly with a protractor. Irreversible inhibition of RLAR by NAP-HEX-Q, as a function of the dose of irradiation with either X-rays or light, is consistent with apparent first order kinetics. NAP-HEX-Q is designed as a drug to prevent or reverse diabetic cataract formation by selective photoaffinity inhibition of RLAR with no significant effect on aldose reductase in other tissues. However, when not accessible to light, other potential target-entrapped drugs can be activated by low doses of X-rays at their targeted anatomic sites.