Eucommia lignans alleviate the progression of diabetic nephropathy through mediating the AR/Nrf2/HO-1/AMPK axis in vivo and in vitro / 中国天然药物

Lignans derived from Eucommia ulmoides Oliver (Eucommia lignans) inhibit the progression of inflammatory diseases, while their effect on the progression of diabetic nephropathy (DN) remained unclear. This work was designed to assess the function of Eucommia lignans in DN. The major constituents of Eucommia lignans were analyzed by UPLC-Q-TOF-MS/MS. The binding between Eucommia lignans and aldose reductase (AR) was predicted by molecular docking. Eucommia lignans (200, 100, and 50 mg·kg-1) were used in model animals to evaluate their renal function changes. Rat glomerular mesangial cells (HBZY-1) were transfected with sh-AR, sh-AMPK, and oe-AR in the presence of high glucose (HG) or HG combined with Eucommia lignans to evaluate whether Eucommia lignans affected HG-induced cell injury and mitochondrial dysfunction through the AR/Nrf2/HO-1/AMPK axis. Eucommia lignans significantly attenuated the progression of DN in vivo. Eucommia lignans notably reversed HG-induced upregulation of inflammatory cytokines and mitochondrial injury, while downregulating the levels of Cyto c, caspase 9, AR, and NOX4 in HBZY-1 cells. In contrast, HG-induced downregulation of Nrf2, HO-1 and p-AMPKα levels were abolished by Eucommia lignans. Meanwhile, knockdown of AR exerted similar therapeutic effect of Eucommia lignans on DN progression, and AR overexpression reversed the effect of Eucommia lignans. Eucommia lignans alleviated renal injury through the AR/Nrf2/HO-1/AMPK axis. Thus, these findings might provide evidence for the use of Eucommia lignans in treating DN.

Vasant Kusmakar Ras, an ayurvedic herbo-mineral formulation prevents the development of diabetic retinopathy in rats

Background: Diabetic retinopathy is a slow progressing complication of diabetes mellitus with multifactorial aetiology affecting approximately 80% of diabetics worldwide. Chronic hyperglycemic milieu ofDiabetes induces biochemical changes which contribute to the pathogenesis of Diabetic retinopathy.Objective: The present study examined the protective effect of Vasant Kusumakar Ras, an Ayurvedicherbo-mineral formulation, in diabetic retinopathy.Materials and Methods: Diabetes was induced in rats by intraperitoneal injection of streptozotocin (45mg/kg). Rats were kept without any treatment for period of three weeks for induction of Diabeticretinopathy followed by treatment with Vasant Kusumakar Ras (11.25 mg/kg, p.o) for further 5 weeks.Fasting blood glucose levels, lipid profile and HbA1c were determined. Eye tissue homogenates weresubjected to biochemical analysis to determine the levels of oxidative stress parameters (superoxidedismutase, catalase, reduced glutathione, lipid peroxidation), vascular endothelial growth factor andaldose reductase activity. Histopathological analysis of retinal tissue was conducted using Hematoxylinand Eosin staining.Results: Vasant Kusumakar Ras treatment restored serum lipid profile which was altered in diabetic rats.Treatment with Vasant Kusumakar Ras significantly ameliorated the oxidative stress in eye tissueresulting in decreased lipid peroxidation and increase in endogenous antioxidant levels. Levels of aldosereductase and vascular endothelial growth factor in eye tissue were significantly decreased in VasantKusumakar Ras treated rats. Hematoxylin and Eosin staining indicated that the Vasant Kusumakar Rastreatment significantly restored the normal architecture of the retinal tissue.Conclusion: Vasant Kusumakar Ras exhibits protective effect and prevents the development of Diabeticretinopathy through its effects on multiple biochemical pathways implicated in pathogenesis of Diabeticretinopathy.

Research progress in pathogenesis of diabetic keratopathy / 国际眼科杂志(Guoji Yanke Zazhi)

@#Diabetic keratopathy is one of the common complications of diabetes in the eye, the main clinical manifestations include dry eye diseases, punctate keratitis, slow regeneration of cornea epithelial, recurrent epiththelial erosions, degeneration of corneal sensitivity and corneal edema. The main pathogenesis is AGES, polyol pathway, the changes of proteinases, <i>etc.</i> This article mainly reviews the pathogenesis of its main clinical manifestations,expect to provide new ideas for clinical treatment.

Ultrastructural and proapoptotic-like effects of kaempferol in Giardia duodenalis trophozoites and bioinformatics prediction of its potential protein target

BACKGROUND Kaempferol (KPF) is a flavonoid with antiparasitic activity including experimental giardiasis which mechanism of action is unknown. OBJECTIVE To analyse the cytotoxic effects of KPF on Giardia duodenalis trophozoites and to identify a likely parasite target of this compound. METHODS We used inhibitory concentrations of KPF (IC25, IC50 and IC100) and albendazole (ABZ) as reference drug. The ultrastructure of the trophozoites was analysed by transmission electron microscopy (TEM) whilst apoptosis/necrosis, production of reactive oxygen species (ROS) and cell cycle progression were assessed by flow cytometry (FCM) and confocal laser microscopy (CLM). Ligand-protein docking analyses were carried out using KPF structure from a drug library and crystal structure of a G. duodenalis aldose reductase (GdAldRed) homolog. RESULTS KPF provoked appearance of perinuclear and periplasmic spaces devoid of cytosolic content and multilamellar structures. KPF induced proapoptotic death associated with partial arrest in the S phase without ROS production. Bioinformatics approaches predicted that GdAldRed is a viable KPF target (ΔG = -7.09 kCal/mol), exhibiting 92% structural identity and a similar coupling pattern as its human homolog. CONCLUSIONS KPF exerted a proapoptotic effect on G. duodenalis trophozoites involving partial interruption of DNA synthesis without oxidative stress or structure damage to chromatin and cytoskeletal structures. GdAldRed is a likely target underlying its antigiardial activity.

Protective effect of gigantolon human retinal microvascular endothelial cells induced by high glucose / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To investigate the protective effects of gigantol on aldose reductase(AR)pathway and oxidative stress induced by high glucose in human retinal microvascular endothelial cells(HRMECs).<p>METHODS: HRMECs were cultured and divided into the five groups: normal glucose group, mannitol group,high glucose group, gigantol group and epalrestat group. Cell vitality was detected by the MTS assay, reactive oxygen species(ROS)levels were detected by DCFH-DA fluorescent probe, protein expressions of nuclear factor kappa B(NF-κB)were observed by Western blotting, mRNA levels of AR, hypoxia inducible factor-1α(HIF-1α)and vascular endothelial growth factor(VEGF)were measured by qRT-PCR.<p>RESULTS: DCFH-DA fluorescent probe levels showed that gigantol reduced ROS generation obviously, and protein expressions of NF-κB, mRNA expressions of AR,HIF-1α and VEGF were all decreased. The expression trends of AR and NF-κB in epalrestat group were consistent with gigantol group.<p>CONCLUSION: Gigantol and epalrestat could inhibit the activation of AR/NF-κB pathway, and gigantol also could inhibit high glucose induced oxidative stress and in HRMECs, which may have a protective effect on diabetic retinopathy(DR), and improve angiogenesis.

Epalrestat inhibits PDGF-induced proliferation of rat PASMCs by inhibiting aldose reductase expression / 中国药理学与毒理学杂志

OBJECTIVE To explore the inhibitory effects of epalrestat (EPS) on platelet-derived growth factor (PDGF)-induced rat pulmonary artery smooth muscle cells proliferation by inhibiting aldose reductase (AR) expression.METHODS Primary rat pulmonary arterial smooth muscle cells (PASMCs) were prepared from the pulmonary artery of male 10-week-old Sprague-Dawley rats using explant method.PDGF 30 mg·L-1was given to induce cell proliferation.After PASMCs grew to 70%-80% conflu?ence, AR small-interferring RNA(ARsiRNA) was transfected with Lipofectamine 3000 into PASMCs. After 24 h,the expression and activity of AR were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR),Western blotting and spectrophotometric method,respectively to investigate EPS on PASMCs proliferation and proliferating cell nuclear antigen (PCNA) and collagenⅠexpression induced by PDGF from in vitro. PASMCs (normal control, PDGF 30 mg·L-1, PDGF+EPS 1, 10 and 100 μmol·L-1,EPS 100 μmol·L-1)were treated according to groups.Cell proliferation was measured by BrdU marking and flow cytometry. The expressions of AR, PCNA and collagenⅠwere analyzed with RT-qPCR and Western blotting.RESULTS In cultured PASMCs,compared with normal control group, the application of exogenous PDGF-induced cell proliferation concomitantly up-regulated AR expres?sion and activity (P<0.01), and such effect was abolished by ARsiRNA. Compared with PDGF group, EPS attenuated PDGF-induced proliferation of PASMCs,expression of PCNA,and collagenⅠ(P<0.05, P<0.01),and the inhibitory effect of EPS was accompanied by inhibition of AR expression(P<0.05,P<0.01).CONCLUSION EPS inhibits PDGF-induced proliferation of PASMCs via inhibiting AR expression.

Antidiabetic potential of methanol extracts from leaves of Piper umbellatum L.and Persea americana Mill

Objective:To determine inhibitory activity of methanolic leaf extract of Piper umbellatum and Persea americana (P.americana) (traditionally used in Cameroon against diabetes) on α-glucosidase,β-glucosidase,maltase-gluconmylase,aldose reductase and aldehyde reductase activities,enzymes involved in starch digestion or diabetic complications.Methods:The methanol extracts from Piper umbellatum and P.americana were prepared by maceration.To assess relative efficacy of these extracts,the determination of concentrations that were needed to inhibit 50％ of enzyme activity was done,whereas,gas chromatography-mass spectrum was used to identify components from extracts that may be responsible for the activities.Resullts The tested extracts strongly inhibited α-glucosidase,maltase-glucoamylase,aldose reductase and aldehyde reductase activities with IC50 ranging from (1.07 ± 0.03) to 01.77 + 1.17) μg/mL.Among the tested extracts,P.americana was the most active against sensitive enzymes (IC50 of 1.07 ± 0.03 to 15.63 ± 1.23).But,none of the extracts showed interesting inhibitory effect against β-glucosidase as their percentage inhibitions were less than 16％.From gas chromatographymass spectrum analysis,10 and 8 compounds were identified in Piper umbellatum and P.americana extracts respectively,using NIST library 2014.Conclusions:Results of this study provide the scientific credential for a prospective usage of these plants to treat diabetes.

Antidiabetic potential of methanol extracts from leaves of Piper umbellatum L. and Persea americana Mill

Objective: To determine inhibitory activity of methanolic leaf extract of Piper umbellatum and Persea americana (P. americana) (traditionally used in Cameroon against diabetes) on α-glucosidase, β-glucosidase, maltase-glucoamylase, aldose reductase and aldehyde reductase activities, enzymes involved in starch digestion or diabetic complications. Methods: The methanol extracts from Piper umbellatum and P. americana were prepared by maceration. To assess relative efficacy of these extracts, the determination of concentrations that were needed to inhibit 50% of enzyme activity was done, whereas, gas chromatography-mass spectrum was used to identify components from extracts that may be responsible for the activities. Results: The tested extracts strongly inhibited α-glucosidase, maltase-glucoamylase, aldose reductase and aldehyde reductase activities with IC

Inhibition of Potentilla fruticosa extracts on α-amylase, α-glucosidase and aldose reductase / 中国药科大学学报

@#This study measured the in vitro inhibitory effects of α-amylase(AM), α-glycosidase(AG)and aldose reductase(AR)extraction from Potentilla fruticosa in three solvents: water extract(WE)and 95% methanol extraction of petroleum ether part(MEP), 95% methanol extraction of ethyl acetate part(MEE)and 95% methanol extraction of water part(MEW)through α-amylase inhibitors(AMI), α-glycosidase inhibitors(AGI)and aldose reductase inhibitors(ARI)activity screening models. In vivo effects of different solvents from Potentilla fruticosa on impaired glucose tolerance of mice were also measured. Among them, WE, MEP and MEE exhibited against AMI activity with IC50 values of 0. 432, 1. 193 and 0. 507 mg/mL, respectively. Three solvents against AGI activity with IC50 values of 0. 164, 0. 768 and 0. 466 mg/mL, respectively. Three solvents against ARI activity with IC50 values of 0. 742, 2. 158 and 1. 098 mg/mL, respectively. The study suggests that Potentilla fruticosa in water extract and 95% methanol extraction of ethyl acetate part demonstrated a stronger inhibitory effect on AM, AG and AR. Meanwhile, Potentilla fruticosa in water extract and 95% methanol extraction of ethyl acetate part can be significantly decreased the postprandial blood glucose in mice.

Effects of ligustrazine on blood rheology, aldose reductase and renal function in diabetic nephropathy rats / 中成药

AIM To explore the effects of ligustrazine on blood rheology,aldose reductase (AR) and renal function in diabetic nephropathy (DN) rats.METHODS The DN rat model was established by intraperitoneal injection of streptozotoein (55 mg/kg),rats were randomly divided into five groups,model group,irbesartan [50 mg/(kg · d)] group,high-,middle-and low-dose of ligustrazine [200,100,50 mg/(kg · d)] groups,together with normal control group.All the rats received daily garage for eight successive weeks.At the end of experiment,blood rheology,blood glucose,aldose reductase in erythrocyte and kidney tissue,24 h urinary protein,blood urea nitrogen,creatinine,creatinine clearance and renal function were observed.RESULTS Compared with the model group,blood rheology,blood glucose and renal function in various treatment groups were effectively improved,and aldose reductase activity was significantly decreased (P ＜ 0.05).HE staining and PAS staining showed that the pathological changes in kidney were significantly alleviated.CONCLUSION Ligustrazine can protect kidney of DN rats by ameliorating blood rheology,decreasing blood glucose and inhibiting aldose reductase activity.

Expression of inflammatory factors are increased by sorbitol in lumbar spinal stenosis of diabetic patients / 基础医学与临床

Objective To investigate the related mechanism of ligamentum flavum (LF) hypertrophy in diabetic pa-tients with lumbar spinal canal stenosis ( LSCS ) .Methods Twenty-four diabetes mellitus patients [ DM (+) ] and twenty normoglycemic patients [ DM (-) ] with LSCS were enrolled in this study .Sorbitol in LF was analyzed using D-Sorbitol/Xylitol test kit .The thickness of LF was measured by CT .The structure of LF was observed after HE and Masson's trichrome staining .The cell cycle and proliferation of fibroblastic cell NIH 3T3 line cultured in high glucose were analyzed .Sorbitol of NIH3T3 was detected under different backgrounds in vitro, normal glucose , high glucose and high glucose burdened with aldose reductase inhibitor ( ARI) , Epalrestat .The expression of inflammatory factors was detected by qPCR and Western blot under above different backgrounds .Results LF of diabetic patients exhibi-ted significantly higher level of sorbitol and pro-inflammatory cytokines , TGF-βand of CD68-positive staining than that of the normoglycemic subjects ( P<0.01 ) .The diabetic LF was significantly thicker than that of the controls , and showed evidence of degeneration .The high glucose-cultured fibroblasts exhibited significantly higher levels of sorbitol , pro-inflammatory factors , and TGF-βcompared to the low glucose-cultured cells , and these levels were dose-dependently reduced by treatment with the aldose reductase inhibitor (P<0.05).Conclusions Sorbitol level of the LF is significantly increased in the DM patients with LSCS .Increased sorbitol recruites inflammatory factors and fibrogenic-related factor TGF-βin LF of DM patients with LSCS which may contributes to the LF hypertrophy .

Prevention of the Right Ventricular Remodeling by Epalrestat in Pulmonary Arterial Hypertension Rats and the Underlying Mechanisms / 中国药学杂志

OBJECTIVE: To investigate the protective effect of epalrestat on right ventricular remodeling in a rat model of monocrotaline-induced pulmonary arterial hypertension(PAH). METHODS: PAH rats were induced by a single injection of monocrotaline(60 mg·kg-1, sc) and were administered epalrestat(50 or 100 mg·kg-1) for 4 weeks. At the end of experiment, the right ventricular systolic pressure(RVSP) and mean pulmonary artery pressure(mPAP) were monitored via the right jugular vein catheterization into the right ventricle. Right ventricle(RV) and left ventricle(LV)+septum(S) were isolated and weighed, and ratios of RV/(LV+S)and RV to tibial length were calculated. Right ventricular morphological change was observed by HE staining. Masson's trichrome stain was used to demonstrate collagen deposition. The total antioxidative capacity(T-AOC) and malondialdehyde(MDA) levels in right ventricle were determined according to the manufacturer's instructions. The expression of collagen I, collagen III, AR and NOX4 were analyzed by immunohistochemisty, real-time PCR or Western blot. RESULTS: The results showed that epalrestat treatment for 4 weeks attenuated RVSP, mPAP and right ventricular remodeling index(RV/LV+S and RV/Tibial length) of PAH rats induced by monocrotaline. Furthermore, monocrotaline-induced right ventricular collagen accumulation and collagen I and collagen III expression were both significantly suppressed by epalrestat. The expressions of AR, NOX4 and MDA content were obviously decreased, while the T-AOC was significantly increased in right ventricular from PAH rats with epalrestat treatment. CONCLUSION: These results suggest that epalrestat ameliorates right ventricular remodeling of PAH induced by monocrotaline in rats through its down-regulating of AR and NOX4 expression and collagen accumulation.

In vitro aldose reductase inhibitory potential of fractions isolated from Potentilla fulgens roots.

The present study was investigated to identify the active fraction of P. fulgens with aldose reductase (AR) inhibitory potential. AR is the rate limiting step of polyol pathway implicated in the onset of chronic complications of diabetes. In this study, kidney homogenates of normoglycemic and diabetic mice were used as a source of AR enzyme preparation for in vitro analysis. The Terpenoid/Phenolic (TP) fraction of P. fulgens had the lowest IC50 value (0.152 mg/ml) for AR than the other fractions. TP fraction was separated using thin layer chromatography (TLC) and separated TLC fractions were tested for their AR inhibitory activity. Among the TLC fractions, F-V had the lowest IC50 value (0.156 mg/ml) and was characterized further using High Performance Liquid Chromatography (HPLC), Infra-Red (IR) Spectroscopy and Mass Spectroscopy (MS). F-V showed absorption maxima at λ230 nm and λ280 nm. HPLC profile of this fraction showed the presence of one prominent peak with a retention time of 1.621. IR spectra of the prominent peak indicated the presence of aromatic group which is phenolic in nature. MS of the prominent peak showed m/z ratio of 458.8. The active fraction isolated from P. fulgens has been shown to inhibit AR in normoglycemic and diabetic mice.

Chemical constituents from whole plants of Rehmannia chingii / 中草药

Objective: To investigate the chemical constituents of Rehmannia chingii. Methods: The compounds were isolated from an aqueous extract from the whole plants of R. chingii by a combination of various chromatographic techniques including column chromatography over silica gel and Sephadex LH-20 and reversed-phase HPLC. Their structures were identified by spectroscopic analysis including MS and NMR data. Results: Seventeen compounds were isolated and identified as 8-methyloctahydrocyclopenta[c] pyran-1,3,6,8-tetraol (1), 3,4-dihydroxy-phenethyl alcohol (2), 3-methoxyl-4-hydroxyphenyl alcohol (3), phenylethyl-8-O-β-D-glucopyranoside (4), 3,4-dihydroxy-β-phenethyl-O-α-L-rhamnopyranosyl-(1→3)-O-β-D-glucopyranoside (5), 2-phenylethyl-O-β-D-xylopyranosyl-(1→6)-β-D-glucopyranoside (6), deacyl-martynoside (7), acteoside (8), isoacteoside (9), martynoside (10), isomartynoside (11), jionoside C (12), jionoside A1 (13), jionoside B1 (14), 3,4-dihydroxy-β-phenethyl-O-α-L-rhamnopyranosyl-(1→3)-O-β-D-galacopyranosyl-(1→6)-4-O-caffeoyl-β-D-glucopyranoside (15), cistanoside F (16), and isocistanoside F (17). Conclusion: Among the isolated seventeen compounds, compound 1 is a new compound named rehmachinin, and compounds 16-17 are isolated from the plants of Rehmannia Libosch. ex Fisch. et Mey. for the first time. In the preliminary assays, compounds 9, 12, and 14-16 exhibit the obvious inhibition against aldose reductase.

Aldose Reductase Inhibitory Alkaloids from Corydalis ternata

A methanolic extract of Corydalis ternata having aldose reductase inhibitory activity was examined as a possible aldose reductase (ALR2) inhibitor, a key enzyme involved in diabetic complications. Seven alkaloids, tetrahydrocoptisine (1), corydaline (2), tetrahydropalmatine (3), isocorybulbine (4), corybulbine (5), dehydrocorydaline (6), and N-methyltetrahydroberbinium (7) were isolated from CHCl₃ fraction of C. ternata methanol extract. Among them, compounds 1, 5, and 7 exhibited 5.04 ± 1.97%, 5.00 ± 1.26%, and 1.80 ± 2.33% inhibitions, respectively at 40 µM. The activities of the single compounds were not comparable to that of the whole extract, suggesting that the whole combination of each single compound was responsible for the activity of the extract as shown in many cases of natural medicines. Even though this is the second report on aldose reductase inhibition activity of C. ternata, recombinant human aldose reductase was employed in this study unlike in the previous report. Furthermore, the aldose reductase inhibitory activities of isocorybulbine, corybulbine, and N-methyltetrahydroberbinium, to the best of our knowledge, were evaluated for the first time in this study. These results suggest a use of the extract of C. ternata for ameliorating diabetic complications.

Effect of esculin on the lens injury induced by D-galactose in rats / 中国药学杂志

OBJECTIVE: To investigate the effect of esculin (ES) against lens injury induced by D-galactose in rats. METHODS: Male SD rats were randomly divided into five groups normal control group (control), D-galactose model group (model), ES 30 mg·kg-1 administered group (ES30), ES 100 mg·kg-1 administered group (ES100) and aminoguanidine 100 mg·kg-1 administered group (AG). After treatment, blood glucose and glycosylated serum protein (GSP) content in serum were measured. The content of malondialdehyde (MDA), the level of glutathione (GSH), and the activity of aldose reductase (AR) in lens were also assayed. RESULTS: Compared with control group, the level of blood glucose was significantly increased (P<0.01) in D-galactose model rats. In addition, in the lens tissue of D-galactose-induced rats, the content of MDA was significantly decreased (P<0.05), the level of GSH was significantly increased (P<0.05), and the activity of AR was significantly decreased (P<0.05). However, co-treatment with ES 30 mg·kg-1 significantly decreased the level of GSP in serum(P<0.05), decreased the content of MDA (P<0.05), increased the level of GSH (P<0.05), and inhibited the activity of AR in lens (P<0.05). CONCLUSION: Esculin could improve lens injury induced by D-galactose in rats. The mechanism may be related with increasing GSH level, decreasing MDA production, and inhibiting AR activity.

Esculetin, a Coumarin Derivative, Inhibits Aldose Reductase Activity in vitro and Cataractogenesis in Galactose-Fed Rats

Naturally occurring coumarin compounds have received substantial attention due to their pharmaceutical effects. Esculetin is a coumarin derivative and a polyphenol compound that is used in a variety of therapeutic and pharmacological strategies. However, its effect on aldose reductase activity remains poorly understood. In this study, the potential beneficial effects of esculetin on lenticular aldose reductase were investigated in galactose-fed (GAL) rats, an animal model of sugar cataracts. Cataracts were induced in Sprague-Dawley (SD) rats via a 50% galactose diet for 2 weeks, and groups of GAL rats were orally treated with esculetin (10 or 50 mg/kg body weight). In vehicle-treated GAL rats, lens opacification was observed, and swelling and membrane rupture of the lens fiber cells were increased. Additionally, aldose reductase was highly expressed in the lens epithelium and superficial cortical fibers during cataract development in the GAL rats. Esculetin reduced rat lens aldose reductase (RLAR) activity in vitro, and esculetin treatment significantly inhibited lens opacity, as well as morphological alterations, such as swelling, vacuolation and liquefaction of lens fibers, via the inhibition of aldose reductase in the GAL rats. These results indicate that esculetin is a useful treatment for galactose-induced cataracts.

Erythrocyte enzymes of Glyoxalase system as indicators of beneficial effects of antihyperglycemic agents in Type 2 Diabetes.

Background: Methylglyoxal (MG), a product of sustained hyperglycemia, is a reactive carbonyl toxin responsible for development of complications in diabetes. Glyoxalase system detoxify MG to prevent complications. Some antihyperglycemic agents, may inhibit deleterious effects of MG by independent mechanisms. It was considered worthwhile to identify such agents and to find out whether changes observed in the erythrocyte levels of Glyoxalase I, Glyoxalase II, Aldose Reductase & D-Lactate are indicators of the beneficial effects through their direct action on MG, or merely a result of good glycemic control in response to treatment. Methods: The glyoxalase system was characterized in erythrocytes of blood samples from patients with Type 2 Diabetes (n = 147), and normal healthy control subjects (n = 40). Diabetics were divided into groups based on presence or absence of complications; & further divided into subgroups based on medication with sulphonylurea, metformin, insulin and combination therapy. Results: Erythrocyte Glyoxalase I, Glyoxalase II, Aldose Reductase, and D-Lactate levels significantly increased in all diabetics, (p<0.001) relative to controls. A maximum rise of enzymes in T2D with complications was observed as compared to patients without complications (p<0.001). Inadequate glycemic control was observed in all diabetics, and enzyme levels significantly declined in groups treated with metformin, either as monotherapy or in combination with insulin. Conclusions: Enzymes of Glyoxalase system indicate beneficial effects of metformin. Metformin reduces MG and minimizes worsening glycemic control leading to complications. Metformin renders protection through mechanism independent of its antihyperglycemic action.

The role of enzymes of the glyoxalase system in relation to complications in type II diabetes mellitus.

Background: Metabolism of methylglyoxal by the glyoxalase system may be linked to the development of diabetic complications. It was considered worthwhile to find out whether changes observed in the levels of glyoxalase I, glyoxalase II, aldose reductase & D-lactate are prognostic indicators for the development of complications of diabetes or merely reflect the result of changes associated with complications. Methods: The glyoxalase system was characterized in erythrocytes of blood samples from patients with type II diabetes mellitus (n=177), and normal healthy control subjects (n=40). Diabetics were divided into 3 main groups based on presence or absence of complications. Results: The concentrations of RBC glyoxalase I, glyoxalase II, aldose reductase, and D-lactate were significantly increased in all groups of diabetic patients, (P <0.001) relative to controls. Comparison between groups showed maximum rise of enzymes in group I and group III (P <0.001); and maximum rise of D-lactate in group III (P <0.001). Within the groups of patients with complications, enzyme levels were markedly increased in patients with IHD/PVD (ischaemic heart disease/peripheral vascular disease) and decreased in patients with nephropathy. Conclusion: Results of this study suggests a positive relationship between increased activity of erythrocyte enzymes of glyoxalase system and poor or moderate glycemic control. The increased enzyme levels in patients without complications indicate their role as prognostic markers for development of complications. Molecular mechanisms for development of Nephropathy appear to be different from those of Neuropathy and Retinopathy.

Effect of kaempferol on correlation factors of chronic complications of type 2 diabetic rats / 中草药

Objective: To observe the effect of kaempferol on the correlation factors of chronic complications of type 2 diabetic rats. Methods: Feeding high-fat diet combined with ip injection of 30 mg/kg STZ in rats to make the model of type 2 diabetes. Rats in every administration group were given respective drug (50, 100, and 200 mg/kg), and set the model, normal control, and positive control (metformin hydrochloride 0.2 g/kg) groups. After 10 weeks, using glucose oxidase to measure blood glucose of rats in each group; Radioimmunoassay was used to measure INS and get ISI. Measuring the contents of TG, HDL-C, LDL-C, SOD, AR, IL-6, TNF-α, and MDA was detected by TBA. Results: Compared with diabetic model group, kaempferol administration can reduce blood glucose and insulin resistance, restore normal blood lipid levels, along with reducing MDA, AR, TNF-α, and IL-6 levels and increasing SOD levels. Conclusion: Kaempferol can prevent and treat the chronic complications of type 2 diabetic rats by reducing blood glucose, insulin resistance, reducing the AR pathway as well as anti-oxidation and anti-inflammation.