Rat Lens Aldose Reductase Research Articles

Vicenin 2 isolated from Artemisia capillaris exhibited potent anti-glycation properties

Vicenin 2, isolated from a traditionally used medicinal plant Artemisia capillaris, is a 6,8-di-C-glucoside of apigenin which has been previously reported to possess a wide variety of pharmacological activities including antioxidant, anti-inflammatory, anti-cancer, and hepatoprotective. However, there have not been any reports concerning its anti-diabetic potential until now. Therefore, in the present study, we evaluated the anti-diabetic potential of vicenin 2 via α-glucosidase, protein tyrosine phosphatase 1B (PTP1B), rat lens aldose reductase (RLAR), and advanced glycation end products (AGE) formation inhibitory assays. Vicenin 2 strongly inhibited α-glucosidase, PTP1B, and RLAR in the corresponding assays. In addition, vicenin 2 inhibited the formation of both fluorescent AGE and nonfluorescent AGE, e.g., CML, as well as the level of fructosamine in glucose–fructose-induced bovine serum albumin (BSA) glycation. In the test system, vicenin 2 suppressed glycation-induced protein oxidation by attenuating the formation of protein carbonyl groups as well as by inhibiting the modification of protein thiol groups. Moreover, vicenin 2 was found to be a potent inhibitor of glycation-induced formation of amyloid cross-β structures in BSA. Taken together, vicenin 2 might be a useful lead for the development of multiple target-oriented therapeutic modalities for the treatment of diabetes and diabetes-associated complications.

DW1029M, a novel botanical drug candidate, inhibits advanced glycation end-product formation, rat lens aldose reductase activity, and TGF-β1signaling

DW1029M is a botanical extract consisting of Morus bark and Puerariae radix, produced by Dong-Wha Pharmaceutical, for nephroprotective drug development; it has been in phase II clinical trials in Korea. In our mechanistic investigations, we found that DW1029M inhibits advanced glycation end products (AGEs), rat lens aldose reductase (RLAR), and transforming growth factor (TGF)-β1 signaling, all of which are implicated in diabetic complications such as diabetic nephropathy and diabetic retinopathy. DW1029M inhibits AGE formation via Fe(2+) chelation. The extract contains 13 active constituents that inhibit AGE formation, 8 active constituents that inhibit RLAR activity, and 1 inhibitor of TGF-β1 signaling. Our results suggest DW1029M protects against diabetic nephropathy via blockade of AGE formation, RLAR activity, and TGF-β1 signaling.

2-Chloro-1,4-naphthoquinone derivative of quercetin as an inhibitor of aldose reductase and anti-inflammatory agent

The ability of flavonoids to affect multiple key pathways of glucose toxicity, as well as to attenuate inflammation has been well documented. In this study, the inhibition of rat lens aldose reductase by 3,7-di-hydroxy-2-[4-(2-chloro-1,4-naphthoquinone-3-yloxy)-3-hydroxy-phenyl]-5-hydroxy-chromen-4-one (compound 1), was studied in greater detail in comparison with the parent quercetin (compound 2). The inhibition activity of 1, characterized by IC50 in low micromolar range, surpassed that of 2. Selectivity in relation to the closely related rat kidney aldehyde reductase was evaluated. At organ level in isolated rat lenses incubated in the presence of high glucose, compound 1 significantly inhibited accumulation of sorbitol in a concentration-dependent manner, which indicated that 1 was readily taken up by the eye lens cells and interfered with cytosolic aldose reductase. In addition, compound 1 provided macroscopic protection of colonic mucosa in experimental colitis in rats. At pharmacologically active concentrations, compound 1 and one of its potential metabolite 2-chloro-3-hydroxy-[1,4]-naphthoquinone (compound 3) did not affect osmotic fragility of red blood cells.

The effects of C-glycosylation of luteolin on its antioxidant, anti-Alzheimer's disease, anti-diabetic, and anti-inflammatory activities.

To investigate the effect of C-glycosylation at different positions of luteolin, the structure-activity relationships of luteolin and a pair of isomeric C-glycosylated derivatives orientin and isoorientin, were evaluated. We investigated the effects of C-glycosylation on the antioxidant, anti-Alzheimer's disease (AD), anti-diabetic and anti-inflammatory effects of luteolin and its two C-glycosides via in vitro assays of peroxynitrite (ONOO(-)), total reactive oxygen species (ROS), nitric oxide (NO), 1,1-diphenyl-2-picrylhydraxyl (DPPH), aldose reductase, protein tyrosine phosphatase 1B (PTP1B), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor cleaving enzyme 1 (BACE1), and cellular assays of NO production and inducible nitric oxide synthase (iNOS)/cyclooxygenase-2 expression in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Of the three compounds, isoorientin showed the highest scavenging activity against DPPH, NO, and ONOO(-), while luteolin was the most potent inhibitor of ROS generation. In addition, luteolin showed the most potent anti-AD activity as determined by its inhibition of AChE, BChE, and BACE1. With respect to anti-diabetic effects, luteolin exerted the strongest inhibitory activity against PTP1B and rat lens aldose reductase. Luteolin also inhibited NO production and iNOS protein expression in LPS-stimulated macrophages, while orientin and isoorientin were inactive at the same concentrations. The effects of C-glycosylation at different positions of luteolin may be closely linked to the intensity and modulation of antioxidant, anti-AD, anti-diabetic, and anti-inflammatory effects of luteolin and its C-glycosylated derivatives.

Comparison of biological activities of Glycyrrhiza glabra and G. uralensis

The biological activities of Glycyrrhiza (GLs) extracts (GL-1, Glycyrrhiza glabra from Eumseong, Korea; GL-2, G. uralensis from Eumseong, Korea; GL-3, G. uralensis from Yeongcheon, Korea; GL-4, G. uralensis from Neimenggu, China: GL-5, G. uralensis purchased from Korea Medicine Herbal Association, Korea) were investigated. G. uralensis (GLs-2, -3, -4, and -5) extracts exhibited higher free radical scavenging activity against DPPH and OH radicals than G. glabra (GL-1). In addition, all GLs had antibacterial activity against E. coli, S. aureus, and H. pylori. GL-3 inhibited the growth of E. coli and S. aureus, while GL-1 had antibacterial activity against H. pylori. All GL extracts tested inhibited the lipopolysaccharide- and interferon-γ-induced inflammatory activity of RAW 264.7 cells. G. glabra and G. uralensis reduced NO generation. GL-3 also inhibited the growth of AGS human gastric adenocarcinoma cells. GLs-3 and -4 showed the inhibition of rat lens aldose reductase. GL-4 had a higher total content of glycyrrhizin (1), glycyrrhetinic acid (2), glabridin (3), and isoliquiritigenin (4). G. uralensis (GLs-2, -3, -4, and -5) is thus more effective than G. glabra (GL-1).

Caffeoylated Phenylpropanoid Glycosides from Brandisia hancei Inhibit Advanced Glycation End Product Formation and Aldose Reductase in Vitro and Vessel Dilation in Larval Zebrafish in Vivo

In our continuing efforts to identify effective naturally sourced agents for diabetic complications, five caffeoylated phenylpropanoid glycosides, acteoside (1), isoacteoside (2), poliumoside (3), brandioside (4), and pheliposide (5) were isolated from the 80% EtOH extract of Brandisia hancei stems and leaves. These isolates (1-5) were subjected to an in vitro bioassay evaluating their inhibitory activity on advanced glycation end product formation and rat lens aldose reductase activity. All tested compounds exhibited significant inhibition of advanced glycation end product formation with IC50 values of 4.6-25.7 µM, compared with those of aminoguanidine (IC50=1,056 µM) and quercetin (IC50=28.4 µM) as positive controls. In the rat lens aldose reductase assay, acteoside, isoacteoside, and poliumoside exhibited greater inhibitory effects on rat lens aldose reductase with IC50 values of 0.83, 0.83, and 0.85 µM, respectively, than those of the positive controls, 3,3-tetramethyleneglutaric acid (IC50=4.03 µM) and quercetin (IC50=7.2 µM). In addition, the effect of acteoside on the dilation of hyaloid-retinal vessels induced by high glucose in larval zebrafish was investigated. Acteoside reduced the diameters of high glucose-induced hyaloid-retinal vessels by 69% at 10 µM and 81% at 20 µM, compared to the high glucose-treated control group. These results suggest that B. hancei and its active components might be beneficial in the treatment and prevention of diabetic vascular complications.

Effects of C-glycosylation on anti-diabetic, anti-Alzheimer’s disease and anti-inflammatory potential of apigenin

Apigenin has gained particular interests in recent years as a beneficial and health promoting agent because of its low intrinsic toxicity. Vitexin and isovitexin, naturally occurring C-glycosylated derivatives of apigenin, have been known to possess potent anti-diabetic, anti-Alzheimer’s disease (anti-AD), and anti-inflammatory activities. The present study was designed to investigate the anti-diabetic, anti-AD, and anti-inflammatory potential of apigenin and its two C-glycosylated derivatives, vitexin and isovitexin by in vitro assays including rat lens aldose reductase (RLAR), human recombinant aldose reductase (HRAR), advanced glycation endproducts (AGEs), protein tyrosine phosphatase 1B (PTP1B), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), β-site amyloid precursor (APP) cleaving enzyme 1 (BACE1), and nitric oxide (NO), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Among them, isovitexin was found as the most potent inhibitor against RLAR, HRAR, AGE, AChE, and BChE while vitexin showed the most potent PTP1B inhibitory activity. Despite the relatively weak anti-diabetic and anti-AD potentials, apigenin showed powerful antiinflammatory activity by inhibiting NO production and iNOS and COX-2 expression while vitexin and isovitexin were inactive. Therefore, it could be speculated that C-glycosylation of apigenin at different positions might be closely linked to relative intensity of anti-diabetic, anti-AD, and anti-inflammatory potentials.

Kinetics and molecular docking studies of an anti-diabetic complication inhibitor fucosterol from edible brown algae Eisenia bicyclis and Ecklonia stolonifera

In the present study, we investigated the anti-diabetic potential of fucosterol by evaluating the ability of this compound to inhibit rat lens aldose reductase (RLAR), human recombinant aldose reductase (HRAR), protein tyrosine phosphatase 1B (PTP1B), and α-glucosidase. Fucosterol displayed moderate inhibitory activity against RLAR, HRAR, and PTP1B. However, it showed weak or no activity against AGE formation and α-glucosidase. In addition, our kinetic study revealed that fucosterol showed a mixed type inhibition against RLAR and HRAR, while it noncompetitively inhibited PTP1B. Since fucosterol inhibited aldose reductase (AR), it holds great promise for use in the treatment of diabetic complications. Therefore, we predicted the 3D structure of AR in rat and human using the Autodock program to simulate binding between AR and fucosterol and evaluate the binding site-directed inhibition of AR by fucosterol. Results of the docking simulations of fucosterol demonstrated negative binding energies (−8.2kcal/mol for RLAR and −8.5kcal/mol for HRAR), which indicated a higher affinity and tighter binding capacity of fucosterol for the active site of the enzyme. In particular, the hydrophobic ring system and the aliphatic side chain of fucosterol were found to be tightly bound in a specificity pocket through apolar amino acid residues on AR, while the anion binding site on AR interacts with the 3-hydroxyl group and the double bond on the side chain of fucosterol. The results of the present study clearly demonstrated the potential of using fucosterol for the management and treatment of diabetes and diabetes-associated complications.

Inhibition of aldose reductase by Aegle marmelos and its protective role in diabetic cataract

Ethnopharmacological relevanceAegle marmelos (L.) Corr. Serr. (Aegle marmelos) leaves were extensively used in the Ayurvedic, Unani and Siddha systems of Indian medicine as an anti-diabetic agent, which serves as hypoglycemic agent. However, the significance of this plant on secondary complications of diabetes such as cataract remained unknown. The aim of the study was to investigate the possible anti-cataractous activity of Aegle marmelos against streptozotocin (STZ) induced diabetic cataract in rats. Materials and methodsAegle marmelos leaf extract was prepared using three different solvents (petroleum ether, ethyl acetate and methanol) and tested for inhibition against rat lens aldose reductase (AR), a key enzyme of polyol pathway. Furthermore, the pharmacological potential of Aegle marmelos extract was investigated against osmotic stress induced opacification of lens in ex vivo organ culture and streptozotocin (STZ) induced diabetic cataract in rats. ResultsEthyl acetate extract of Aegle marmelos inhibited rat lens AR in vitro with an IC50 value of ∼15µg/ml. This extract also prevented the hyperglycemia induced increase in AR activity, sorbitol accumulation and opacification of rat lens in ex vivo lens organ culture. Supplementation of ethyl acetate extract of Aegle marmelos to STZ-induced diabetic rats decreased the blood glucose levels due to hyperglycemia and inhibited the AR activity and delayed cataract progression in dose dependent manner. α-crystallin isolated from diabetic rats fed with Aegle marmelos showed improved chaperone activity than that of isolated from rats naïve to Aegle marmelos. ConclusionThis study indicates that ethyl acetate extract of Aegle marmelos has pharmacologically active components with a potential to inhibit rat lens AR and consequential decrease in osmotic stress. Besides this, the present study also demonstrates that the extract prevented loss of antioxidants contributing to the integrity of α-crystallin's chaperone activity and thereby delaying cataract.

Analysis of the inhibitory activity of Abeliophyllum distichum leaf constituents against aldose reductase by using high-speed counter current chromatography

We isolated five phenolic glycosides (acteoside, eutigoside B, isoacteoside, rutin and cornoside) from Abeliophyllum distichum leaves by high-speed counter current chromatography (HSCCC) using a solvent system of ethyl acetate:n-butanol:water (8:0.7:5). We determined the purity of the 5 compounds by high-performance liquid chromatography, and confirmed their chemical structures by using nuclear magnetic resonance data. We examined the inhibitory effect of these compounds on rat lens aldose reductase. Among these compounds, acteoside (1) showed the most potent inhibitory effect, with an IC₅₀ value of 1.39 μM. The inhibitory effect of 1 was 5.0 times greater than that of quercetin (7.05 μM), which was used as a positive control. These results suggest that acteoside may be a promising agent for the prevention or treatment of diabetic complications. Moreover, HSCCC is a promising method for the isolation and purification of biologically active compounds from natural products.

Aldose Reductase Inhibitory Compounds from Xanthium strumarium

As part of our ongoing search for natural sources of therapeutic and preventive agents for diabetic complications, we evaluated the inhibitory effects of components of the fruit of Xanthium strumarium (X. strumarium) on aldose reductase (AR) and galactitol formation in rat lenses with high levels of glucose. To identify the bioactive components of X. strumarium, 7 caffeoylquinic acids and 3 phenolic compounds were isolated and their chemical structures were elucidated on the basis of spectroscopic evidence and comparison with published data. The abilities of 10 X. strumarium-derived components to counteract diabetic complications were investigated by means of inhibitory assays with rat lens AR (rAR) and recombinant human AR (rhAR). From the 10 isolated compounds, methyl-3,5-di-O-caffeoylquinate showed the most potent inhibition, with IC₅₀ values of 0.30 and 0.67 μM for rAR and rhAR, respectively. In the kinetic analyses using Lineweaver-Burk plots of 1/velocity and 1/substrate, methyl-3,5-di-O-caffeoylquinate showed competitive inhibition of rhAR. Furthermore, methyl-3,5-di-O-caffeoylquinate inhibited galactitol formation in the rat lens and in erythrocytes incubated with a high concentration of glucose, indicating that this compound may be effective in preventing diabetic complications.

The inhibitory activities of the edible green alga Capsosiphon fulvescens on rat lens aldose reductase and advanced glycation end products formation

Accumulating evidence suggests that inhibitors of aldose reductase (AR) may prevent hyperglycemia-induced long-term complications in diabetes mellitus. In the present study, we evaluated the AR inhibitory potential of ethanolic (EtOH) extracts from 22 seaweed species. AR inhibitory activities of the selected seaweed species were evaluated using the rat lens aldose reductase (RLAR) inhibitory assay. All extracts exhibited RLAR inhibitory activity, which ranged from 5.87 to 92.71 % at a concentration of 50 μg/mL. Since Capsosiphon fulvescens exhibited significant inhibitory potential and is a frequently used foodstuff, it was selected for a detailed investigation using RLAR and advanced glycation end products (AGE) formation inhibitory assays. Among the different solvent-soluble fractions, the CH2Cl2, EtOAc, and n-BuOH fractions showed promising RLAR and AGE formation inhibitory activities. Considering the AR inhibitory potential, CH2Cl2 and EtOAc fractions were selected for chromatographic separation and yielded 11 compounds in which capsofulvesin A, capsofulvesin B, and chalinasterol showed potential RLAR inhibitory activity with the respective IC50 values of 52.53, 101.92, and 345.27 μM. Kinetic studies revealed that capsofulvesin A and chalinasterol exhibited mixed type inhibition, while capsofulvesin B exhibited noncompetitive inhibition. To our knowledge, this is the first report of AR inhibitory activity of the glycolipids capsofulvesin A and capsofulvesin B. Our results clearly indicate the potential RLAR and AGE formation inhibitory activities of C. fulvescens as well as its isolated constituents, which could be further explored to develop therapeutic modalities for the treatment of diabetes and related 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.

2″,4″-&lt;i&gt;O&lt;/i&gt;-Diacetylquercitrin, a Novel Advanced Glycation End-Product Formation and Aldose Reductase Inhibitor from &lt;i&gt;Melastoma sanguineum&lt;/i&gt;

A new flavonoid, 2,″4″-O-diacetylquercitrin (1), along with six known flavonoids (2-7) were isolated from the aerial parts of Melastoma sanguineum. The structure of the new flavonoid was established by extensive spectroscopic studies and chemical evidence. The inhibitory effects of isolated compounds (1-7) on advanced glycation end-products (AGEs) formation and rat lens aldose reductase (RLAR) in vitro were examined. Of the tested compounds, compound 1 was the strongest inhibitor of AGEs, with an IC50 of 11.46±0.44 µm. In the RLAR assay, all tested compounds exhibited greater inhibitory effects on RLAR than that of a positive control, 3,3-tetramethyleneglutaric acid (IC50=28.8±1.5 µm); compound 1 exhibited the strongest RLAR-inhibitory activity, with an IC50 of 0.077±0.003 µm.

Aldose Reductase Inhibitory Activity of Compounds from Zea maysL.

Aldose reductase (AR) inhibitors have a considerable therapeutic potential against diabetes complications and do not increase the risk of hypoglycemia. Through bioassay-guided fractionation of an EtOH extract of the kernel from purple corn (Zea mays L.), 7 nonanthocyanin phenolic compounds (compound 1–7) and 5 anthocyanins (compound 8–12) were isolated. These compounds were investigated by rat lens aldose reductase (RLAR) inhibitory assays. Kinetic analyses of recombinant human aldose reductase (rhAR) were performed, and intracellular galactitol levels were measured. Hirsutrin, one of 12 isolated compounds, showed the most potent RLAR inhibitory activity (IC50, 4.78 μM). In the kinetic analyses using Lineweaver-Burk plots of 1/velocity and 1/substrate concentration, hirsutrin showed competitive inhibition against rhAR. Furthermore, hirsutrin inhibited galactitol formation in rat lens and erythrocytes sample incubated with a high concentration of galactose; this finding indicates that hirsutrin may effectively prevent osmotic stress in hyperglycemia. Therefore, hirsutrin derived from Zea mays L. may be a potential therapeutic agent against diabetes complications.

Inhibitory activity of Aralia continentalis roots on protein tyrosine phosphatase 1B and rat lens aldose reductase

As part of our continuous search for compounds from natural sources that can treat diabetes and its diabetic complications, in the present work, we investigated the protein tyrosine phosphatase 1B (PTP1B) and rat lens aldose reductase (RLAR) inhibitory activities of the roots of Aralia continentalis. The methanol extract showed a potent inhibitory activity against PTP1B and RLAR. Among the tested fractions, the n-hexane fraction exhibited the highest PTP1B inhibitory activity, while the EtOAc fraction showed highest RLAR inhibitory activity. Bioassayguided fractionation of the active n-hexane and EtOAc soluble fractions resulted in the isolation of the diterpenoids; ent-pimara-8(14),15-diene-19-oic acid (continentalic acid, 1); ent-kaur-16-en-19-oic-acid (kaurenoic acid, 2); ent-pimara-8(14),15-diene-19-ol (3); 7-oxo-ent-pimara-8(14),15-diene-19-oic acid (4); 16á-hydroxy-17-isovaleroyloxy-ent-kauran-19-oic acid (5); 17-hydroxy-entkaur-15-en-19-oic acid (6); 15á,16á-epoxy-17-hydroxy-ent-kauran-19-oic acid (7); 16á,17-dihydroxy-ent-kauran-19-oic acid (8); 8á-hydroxy-ent-pimara-15-en-19-ol (9); 4-epirulopezol (10) and 4â-hydroxy-19-nor-(-)-pimara-8(14),15-diene (11), from the n-hexane fraction, and 4-[formy-5-(methoxymethyl)-1H-pyrrol-1-yl] butanoic acid (12); vanillic acid (13); 4-hydroxybenzoic acid (14); protocatechuic acid (15); nicotinic acid (16); aralia cerebroside (17); 5-O-feruloly quinic acid (18) from the EtOAc fraction. Of these, compounds 12∼14, 16 and 18 were isolated from A. continentalis for the first time. Compounds 1∼10 exhibited inhibitory potential against PTP1B, while compounds 12, 17, and 18 were found to be active against RLAR. Taken together, these results clearly demonstrate that the roots of A. continentalis displayed anti-diabetic and antidiabetic properties, which could be further explored to develop therapeutic and preventive agents for the treatment of diabetes and related complications.

Promising antidiabetic potential of fucoxanthin isolated from the edible brown algae Eisenia bicyclis and Undaria pinnatifida

In the present study, we investigated the antidiabetic potential of fucoxanthin via the inhibition of rat lens aldose reductase (RLAR), human recombinant aldose reductase (HRAR), advanced glycation end-product (AGE) formation, protein tyrosine phosphatase 1B (PTP1B), and α-glucosidase. Fucoxanthin displayed potent inhibitory activity against AGE formation and HRAR and RLAR activity. In addition, fucoxanthin showed potent inhibitory activity against PTP1B. However, it did not show α-glucosidase inhibitory activity below 200 μM. In addition, our kinetic study revealed that fucoxanthin competitively inhibited RLAR, while it showed mixed-type inhibition against PTP1B. In order to confirm enzyme inhibition, we predicted the 3D structure of PTP1B using Autodock 4.0 to simulate the binding of fucoxanthin. Docking simulation results demonstrated that three residues of PTP1B (Phe30, Phe52, and Gly183) interact with the two hydroxyl groups of fucoxanthin. In addition, the binding energy was negative (−7.66 kcal/mol), indicating that the three hydrogen bonds may stabilize the open form of the enzyme and potentiate tighter binding to the active site of PTP1B, resulting in more effective PTP1B inhibition. The results of the present study therefore clearly demonstrate the promising potential of fucoxanthin as a therapeutic intervention for the management of diabetes as well as diabetes-associated complications, which could be explored further.

현초에서 분리된 페놀성 화합물들의 흰쥐 수정체 유래 알도즈 환원효소 및 갈락티톨 생성 억제 효과

We evaluated the inhibitor effects of extracts and components of Geranium thunbergii on aldose reductase (AR) and galactitol formation in rat lenses with high levels of galactose as a part of our ongoing search of natural sources for therapeutic and preventive agents for diabetic complications. The inhibitory effects of water, methanol and ethanol extracts of G. thunbergii on rat lens AR (RLAR) were determined. Comparing inhibitory effects of various solvent extracts, ethanol extract showed RLAR inhibitory activity (IC50 values, 5.24 and 6.39 μg/㎖, respectively). The ethanol extract was fractionated to chloroform, ethyl acetate and water. Of these, the ethyl acetate fraction from ethanol extract of G. thunbergii exhibited RLAR inhibitory activity (IC50 value, 2.64 μg/㎖). In order to identify the bioactive components of ethyl acetate soluble fraction of ethanol extract from G. thunbergii, eight compounds, namely gallic acid (1), protocatechuic acid (2), p-hydroxybenzoic acid (3), brevifolin carboxylic acid (4), geraniin (5), ellagic acid (6), kaempferol-3-O-arabinofuranosyl-7-O-rham-nopyranoside (7), kaempferitrin (8) were isolated. The isolates were subjected to in vitro bioassays to evaluate their inhibitory activity on RLAR and galactitol formation in rat lenses. The ellagic tannins (5, 6) and flavonoid (7) exhibited strong inhibitory effects on RLAR. Also, these three compounds (5, 6 and 7) suppressed galactitol accumulation in rat lens under high galactose conditions, demonstrating the potential to prevent galactitol accumulation exo vivo. These results suggest that the extracts and components of G. thunbergii are a promising agent in the prevention or treatment of diabetic complications.

In Vitro and In Vivo Inhibitory Activities of Four Indian Medicinal Plant Extracts and their Major Components on Rat Aldose Reductase and Generation of Advanced Glycation Endproducts

The polyol enzyme aldose reductase (AR) and advanced glycation endproducts (AGEs) play an important role in diabetic complications such as cataracts. The purpose of this study was to investigate four standardized plant extracts used for the treatment of diabetes and related diseases, and their principal components for AR inhibitory activity and to find out their influence in diabetic complications. Thus, Boswellia serrata Triana & Planch. (Burseraceae), Lagerstroemia speciosa (L.) Pers. (Lythraceae), Ocimum gratissimum (L.) (Lamiaceae) and Syzygium cumin (L.) Skeels. (Myrthaceae) and their respective major constituents, boswellic acid, corosolic acid, ursolic acid and ellagic acid, were studied for their inhibitory activity against rat lens AR, rat kidney AR, human recombinant AR and generation of AGEs. In addition, in vivo inhibition of lens galactitol accumulation by the major constituents of the plants in galactose-fed rat has been studied. The results revealed that all the tested extracts and their active ingredients possess significant AR inhibitory actions in both in vitro and in vivo assays with urosolic acid showing the most potent effect. Furthermore, the study indicates the potential of the studied plants and their major constituents as possible protective agents against long-term 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