Background Berberine is one of the main constituents of Coptidis rhizoma （CR） and Cortex phellodendri. In this study, we investigated the beneficial effects of berberine on renal function and its possible mechanisms...Background Berberine is one of the main constituents of Coptidis rhizoma （CR） and Cortex phellodendri. In this study, we investigated the beneficial effects of berberine on renal function and its possible mechanisms in rats with diabetic nephropathy （DN）. Methods Male Wistar rats were divided into three groups： normal, diabetic model, and berberine treatment groups. Rats in the diabetic model and berberine treatment groups were induced to diabetes by intraperitonal injection with streptozotocin （STZ）. Glomerular area, glomerular volume, fasting blood glucose （FBG）, blood urea nitrogen （BUN）, serum creatinine （Cr） and urine protein for 24 hours （UP24h） were measured using commercially available kits. Meanwhile, the activity of superoxide dismutase （SOD）, content of malondialdehyde （MDA） in serum, activity of aldose reductase （AR） and the expression of AR mRNA and protein in kidney were detected by different methods. Results The results showed that oral administration of berberine （200 mg·kg^-1·d^-1） significantly ameliorated the ratio of kidney weight to body weight. Glomerular area, glomerular volume, FBG, BUN, Cr and UP24h were significantly decreased in the berberine treatment group compared with the diabetic model group （P〈0.05）. Berberine treatment significantly increased serum SOD activity and decreased the content of MDA compared with diabetic model group （P 〈0.05）. AR activity as well as the expression of AR mRNA and protein in the kidney was markedly decreased in the berberine treatment group compared with diabetic model group （P 〈0.05）. Conclusion These results suggested that berberine could ameliorate renal dysfunction in DN rats through controlling blood glucose, reduction of oxidative stress and inhibition of the activation of the polyol pathway.展开更多
Epalrestat is a noncompetitive and reversible aldose reductase inhibitor used for the treatment of diabetic neuropathy. This study assumed that epalrestat had a protective effect on diabetic peripheral nerve injury by...Epalrestat is a noncompetitive and reversible aldose reductase inhibitor used for the treatment of diabetic neuropathy. This study assumed that epalrestat had a protective effect on diabetic peripheral nerve injury by suppressing the expression of aldose reductase in peripheral nerves of diabetes mellitus rats. The high-fat and high-carbohydrate model rats were established by intraperitoneal injection of streptozotocin. Peripheral neuropathy occurred in these rats after sustaining high blood glucose for 8 weeks. At 12 weeks after streptozotocin injection, rats were intragastrically administered epalrestat 100 mg/kg daily for 6 weeks. Transmission electron microscope revealed that the injuries to myelinated nerve fibers, non-myelinated nerve fibers and Schwann cells of rat sciatic nerves had reduced compared to rats without epalrestat administuation. Western blot assay and immunohistochemical results demonstrated that after intervention with epalrestat, the activities of antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase gradually increased, but aldose reductase protein expression gradually diminished. Results confirmed that epalrestat could protect against diabetic peripheral neuropathy by relieving oxidative stress and suppressing the polyol pathway.展开更多
OBJECTIVE： To evaluate the efficacy of α-lipoic acid（ALA） plus epalrestat combination therapy in the treatment of diabetic peripheral neuropathy（DPN）. DATA SOURCES： The electronic databases of Pub Med, Medline,...OBJECTIVE： To evaluate the efficacy of α-lipoic acid（ALA） plus epalrestat combination therapy in the treatment of diabetic peripheral neuropathy（DPN）. DATA SOURCES： The electronic databases of Pub Med, Medline, Embase, the Cochrane Library, the Chinese National Knowledge Infrastructure, the Wanfang Database and the Chinese Biomedical Database were used to retrieve relevant studies without language restrictions. The search was conducted from the inception of each database to 7 October 2016. The key terms were（diabetic peripheral neuropathy or diabetic neuropathy or DPN） AND（α-lipoic acid or lipoic acid or thioctic acid） AND epalrestat. DATA SELECTION： All of the eligible studies met the following inclusion criteria：（1） Randomized controlled trials that compared efficacy and safety of epalrestat plus ALA combination therapy versus epalrestat or ALA monotherapy in patients with DPN.（2） The minimum duration of treatment was 2 weeks.（3） The DPN patients were diagnosed using the World Health Organization standardized type 2 diabetes mellitus and DPN criteria.（4） Studies contained at least one measure that could reflect the efficacy of the drug and nerve conduction velocities. Studies in which the control group used epalrestat or ALA combined with other drugs were excluded. Statistical analyses were performed using STATA software for meta-analysis. OUTCOME MEASURES： The primary outcomes were the therapeutic efficacy, median motor nerve conduction velocity（MNCV）, median sensory nerve conduction velocity（SNCV）, peroneal MNCV and peroneal SNCV.RESULTS： Twenty studies with 1894 DPN patients were included, including 864 patients in the ALA plus epalrestat group, 473 in the ALA group and 557 in the epalrestat group. The efficacy of ALA plus epalrestat combination therapy was superior to ALA and epalrestat monotherapies（RR = 1.29, 95% CI： 1.21–1.38; RR = 1.43, 95% CI： 1.34–1.54, respectively）. ALA plus epalrestat combination therapy also significantly improved m展开更多
Diabetes mellitus is not a single disease but is a group of metabolic disorders affecting a huge numlier of population in the world.It is mainly characterized by chronic hyperglycemia,resulting from defects in insulin...Diabetes mellitus is not a single disease but is a group of metabolic disorders affecting a huge numlier of population in the world.It is mainly characterized by chronic hyperglycemia,resulting from defects in insulin secretion or insulin action.It is predicated that the number of diabetes person in the world could reach upto 366 million by the year 2030.Even though the cases of diabetes are increasing day by day,except insulin and oral hypoglycemic drugs no other way of treatment has been successfully developed so far.Thus,the objective of the present review is to provide an insight over the pathophysiological and etiological aspects of diabetes mellitus along with the remedies available for this metabolic disorder.The review also contains brief idea about diabetes mellitus and the experimental screening model with their relevant mechanism and significance mainly used nowadays.Alloxan and streptozotocin are mainly used for evaluating the antidiabetic activity of a particular drug.This review contain list of medicinal plants which have been tested for their antidiabetic activity in the alloxan induced diabetic rat model.From the available data in the literature,it was found that plant having antidiabetic activity is mainly due to the presence of the secondary metabolite.Thus,the information provided in this review will help the researchers for the development of an alternative methods rather than insidin and oral hypoglycemic agents for the treatment of diabetes niellitus,which will minimize the complication associated with the diabetes and related disorder.展开更多
AIM: To study the contribution of tonicity response element binding protein(Ton EBP) in retinal ganglion cell(RGC) death of diabetic retinopathy(DR).METHODS: Diabetes was induced in C57BL/6 mice by five consecutive in...AIM: To study the contribution of tonicity response element binding protein(Ton EBP) in retinal ganglion cell(RGC) death of diabetic retinopathy(DR).METHODS: Diabetes was induced in C57BL/6 mice by five consecutive intraperitoneal injections of 55 mg/kg streptozotocin(STZ). Control mice received vehicle(phosphate-buffered saline). All mice were killed 2mo after injections, and the extent of cell death and the protein expression levels of Ton EBP and aldose reductase(AR) were examined.RESULTS: The Ton EBP and AR protein levels and the death of RGC were significantly increased in the retinas of diabetic mice compared with controls 2mo after the induction of diabetes. Terminal deoxynucleotidyl transferase(Td T)-mediated d UTP nick end labeling(TUNEL)-positive signals co-localized with Ton EBP immunoreactive RGC. These changes were increased in the diabetic retinas compared with controls.CONCLUSION: The present data show that AR and Ton EBP are upregulated in the DR and Ton EBP may contribute to apoptosis of RGC in the DR.展开更多
Objective:To evaluate the aldose reductase inhibitory(ARI)activity of different fractions of Hybanthus enneaspermus for potential use in diabetic cataract.Methods:Total phenol and flavonoid content of different fracti...Objective:To evaluate the aldose reductase inhibitory(ARI)activity of different fractions of Hybanthus enneaspermus for potential use in diabetic cataract.Methods:Total phenol and flavonoid content of different fractions was determined.ARI activity of different fractions in rat lens was investigated in vitro.Results:The results showed significant level of phenolic and flavonoid content in ethyl acetate fraction[total phenol(212.15±0.79 mg/g),total flavonoid(39.11±2.27mg/g)]and aqueous fraction[total phenol(140.62±0.57mg/g),total flavonoid(26.07±1.49 mg/g)]as compared with the chloroform fraction[total phenol(68.56±0.51mg/g),total flavonoid(13.41±0.82mg/g)]and petrolium ether fraction[total phenol(36.68±0.43mg/g),total flavonoid(11.55±1.06mg/g)].There was a significant difference in the ARI activity of each fraction,and it was found to be the highest in ethyl acetate fraction[IC_(50)(49.26±1.76μg/mL)]followed by aqueous extract[IC_(50)(70.83±2.82μg/mL)]and it was least in the petroleum ether fraction[IC_(50)(118.89±0.71μg/mL)].Chloroform fraction showed moderate activity[IC_(50)(98.52±1.80μg/mL)].Conclusions:Different fractions showed significanct amount of ARI activity,where in ethyl acetate fraction it was found to be maximum which may be due to its high phenolic and flavonoid content.The extract after further evaluation may be used in the treatment of diabetic cataract.展开更多
Objective:To assesse the inhibitor) effect of alcoholic extract of two Indian medicinal plants namely Ceasalpinia digyna Rottler and.Alangium lamarckii Thwaits on aldose reductase（AR） of rat lens.Methods:Rats lens w...Objective:To assesse the inhibitor) effect of alcoholic extract of two Indian medicinal plants namely Ceasalpinia digyna Rottler and.Alangium lamarckii Thwaits on aldose reductase（AR） of rat lens.Methods:Rats lens were enucleated through posterior approach and their homogenate was prepared and centrifuged to obtain a clear supernatant for the determination of AR activity and protein content.Results:The alcoholic extract of Ceasalpirda digyna and Alangium lamarckii had a potent inhibitory effect on the lens AR enzyme.The IC<sub>50</sub> values of alcoholic extract of the selected plants were calculated and were（46.29±11.17） and（106.00±5.11）μg/mL,respectively. Quercetin was used as a positive control and its IC<sub>50</sub> value was（2.95±1.53）μg/mL.Conclusions:Thus,it is concluded that alcoholic extracts of the selected plant exhibit significant inhibitory effects on AR in the rat lens in vitro.展开更多
为分析配料(硫化物、糖)组成对高温芝麻饼粕蛋白酶解物(High temperature sesame cake protein hydrolysate,HTSPH)制备肉味香精的影响,首先固定木糖与HTSPH含量,考察5种硫化物如半胱氨酸(LCys)、甲硫氨酸(L-Met)、硫胺素(VB1)对美拉德...为分析配料(硫化物、糖)组成对高温芝麻饼粕蛋白酶解物(High temperature sesame cake protein hydrolysate,HTSPH)制备肉味香精的影响,首先固定木糖与HTSPH含量,考察5种硫化物如半胱氨酸(LCys)、甲硫氨酸(L-Met)、硫胺素(VB1)对美拉德反应产物(Maillard reaction products,MRPs)的感官特性、挥发性成分、pH、褐变与糖基化程度的影响,随后对比木糖、核糖、半乳糖等9种糖与L-Cys、HTSPH反应得到MRPs的特性差异,最后,混料试验考察L-Cys、木糖、HTSPH三者组成对MRPs感官特性与挥发性成分影响。结果显示,不同硫化物形成MRPs的挥发性成分组成差异明显,L-Cys的MRPs肉味突出,感官评价得分最高(69.32±1.34)。对比不同糖的MRPs的性质组成发现,戊糖的MRPs中感官评价得分显著高于已糖的MRPs,其挥发性成分中富含肉香味成分,木糖是适宜由HTSPH制作肉味香精的糖类。混料试验表明L-Cys、木糖与HTSPH组成会显著影响MRPs风味特征。偏最小二乘回归分析发现22种关键挥发性成分。5-甲基-2-噻吩甲醛、二糠基二硫醚、5-乙基噻吩-2-甲醛、4,6-二甲基-1H,3H-噻吩并[3,4-c]噻吩、苯甲醛、2-糠基2-甲基-3-呋喃基二硫化物、2-糠硫醇与感官得分正相关。本研究为高温芝麻饼粕制备肉味香精提供理论指导。展开更多
Carbohydrate metabolism disorders(CMDs),such as diabetes,galactosemia,and mannosidosis,cause ciliopathy-like multiorgan defects.However,the mechanistic link of cilia to CMD complications is still poorly understood.Her...Carbohydrate metabolism disorders(CMDs),such as diabetes,galactosemia,and mannosidosis,cause ciliopathy-like multiorgan defects.However,the mechanistic link of cilia to CMD complications is still poorly understood.Herein,we describe significant cilium disassembly upon treatment of cells with pathologically relevant aldoses rather than the corresponding sugar alcohols.Moreover,environmental aldehydes are able to trigger cilium disassembly by the steric hindrance effect of their formyl groups.Mechanistic studies reveal that aldehydes stimulate extracellular calcium influx across the plasma membrane,which subsequently activates the calmodulin-Aurora A-histone deacetylase 6 pathway to deacetylate axonemal microtubules and triggers cilium disassembly.In vivo experiments further show that Hdac6 knockout mice are resistant to aldehyde-induced disassembly of tracheal cilia and sperm flagella.These findings reveal a previously unrecognized role for formyl group-mediated cilium disassembly in the complications of CMDs.展开更多
The formation of advanced glycation end-products （AGEs） and aldose reductase （AR） activity have been implicated in the development of diabetic complications. Our study sought to characterize the capacities of elev...The formation of advanced glycation end-products （AGEs） and aldose reductase （AR） activity have been implicated in the development of diabetic complications. Our study sought to characterize the capacities of eleven herbal extracts against the formation of AGEs and the AR activity. An ultrahigh performance liquid chromatography and tandem mass spectrometry （UPLC-MS/MS） method was used for the detection of AR activity and the screening of AR inhibitors in this research. The amount of sorbitol from each analyte was directly detected using the multiple reaction monitoring mode and the sorbitol level could be reduced via the addition of an inhibitor. Moreover, the BSA/glucose （fructose） system was applied to investigate their inhibitory activities of AGEs formation in glycation model reactions. Compared with other screened herbs used in our study, Flos Sophorae lrnrnaturus and Radix Scutellariae seemed to be more effective on inhibiting the formation of AGEs and AR activity. The inhibiting capacities of herbal extracts against AR activity and AGEs formation may be correlated with the bioactive components of the herbal extracts. The differences were correlated with the amount of polyphenol and flavonoid components. In the study, we have investigated the potential anti-hyperglycemic bioactivity of eleven herbal extracts in vitro, which could provide a reference for further in vivo research in the prevention and treatment of diabetic complications.展开更多
Objective： To compare the effects of different methods of anesthesia and analgesia on the activities of phosphofructokinase（PFK）, glucose-6-phosphate dehydrogenase（G-6PD） and aldose reductase（AR） in erythrocyte...Objective： To compare the effects of different methods of anesthesia and analgesia on the activities of phosphofructokinase（PFK）, glucose-6-phosphate dehydrogenase（G-6PD） and aldose reductase（AR） in erythrocytes and levels of plasma glucose and stress hormones in patients undergoing esophagus surgery. Methods： Sixty-two patients scheduled for esophagus surgery were randomly divided into three groups： group Ⅰ （n = 20） receiving only general anesthesia（GA） followed by intravenous patient controlled analgesia（PCA） with fentanyl 15 μg/kg. The other two groups receiving both general anesthesia combined with thoracic epidural anesthesia （GEA） and either intravenous PCA with fentanyl 15 μg/kg （group Ⅱ, n = 21） or thoracic epidural analgesia（TEA） with 0.125% ropivacaine and 0.0002% fentanyl mixture（group Ⅲ, n = 21） after the operation. Venous blood samples were collected for measurements of PFK, G-rPD and AR activities in erythrocytes and plasma glucose, cortisol, epinephrine and norepinephrine before induction （T1）, 60 min following the incision （T2）, 60 min（T3） after operation, on the lst（T4） and 2nd postoperative day（T5）. Results： The activities of PFK decreased（P 〈 0.01 or P = 0.004） and the activities of G-6PD and AR increased（P 〈 0.01） in groups Ⅰ and Ⅱ on T4 compared with those on T1 Between the two groups, the activities of these enzymes in group Ⅱ changed less than those of group Ⅰ （P 〈 0.01 or P 〈 0.05）. These enzymes activities changed slightly in group Ⅲ on T4（P 〉 0.05）. There were significant differences between group Ⅲand the other two groups（P 〈 0.0l or P 〈 0.05）. The levels of plasma glucose increased significantly on T2（P 〈 0.01）, reached peak values on Ta（P 〈 0.01） and fell on T5 in the three groups. Compared to those of groups Ⅰ and Ⅱ, the values of plasma glucose in group Ⅲwere lower on T4 and T5（P 〈 0.05 or P 〈 0.01）. The cortisol concentration in each gr展开更多
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 ...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-AMPKαlevels 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.展开更多
A series of Benzisolselenazolone (BISA) derivatives were synthesized and evaluated for their antibacterial activities againstE coli. by using LKB-2277 bioactivity monitor. Other bioactivities were tested by the method...A series of Benzisolselenazolone (BISA) derivatives were synthesized and evaluated for their antibacterial activities againstE coli. by using LKB-2277 bioactivity monitor. Other bioactivities were tested by the method of High Throughput Screening for pharmaceutical activity compounds (HTP) BISA derivatives 3b, at the concentration of 40 μg/mL, showed 100%antibacterial activity and 62%inhibition rate of aldose reductase (at the concentration of 5μg/mL). These new compound structures have determined by IR,1H NMR and MS spectra.展开更多
AIM:To investigate the aldose reductase(AR)inhibition capacity of astragalin(AST)against streptozoticin-induced diabetic cataracts(DCs)in rats.METHODS:Ex vivo investigations were conducted by treating the lens of a go...AIM:To investigate the aldose reductase(AR)inhibition capacity of astragalin(AST)against streptozoticin-induced diabetic cataracts(DCs)in rats.METHODS:Ex vivo investigations were conducted by treating the lens of a goat placed for 72h in artificial aqueous humor(AAH)of pH 7.8 at room temperature with cataract-causing substance(55 mmol/L of galactose)and in vivo studies were performed on rats via induction with streptozotocin.AST was administered at different dose levels and scrutinize for DC activity.RESULTS:In diabetic rats,AST improved the body weight,blood insulin,and glucose as well as the levels of galactitol in a dose-dependent way,other biochemical parameters i.e.inflammatory mediators and cytokines,and also suppress AR activity.The level of the antioxidant parameters such as superoxide dismutase(SOD),catalase(CAT),and glutathione(GSH)activity were also altered on a diabetic lens after the administration of the AST.CONCLUSION:AST protects against lens opacification to avoid cataracts and polyols formation,indicating that it could be used as a potential therapeutic agent for diabetes.展开更多
Purpose:Patients with diabetes mellitus have an elevated chance of developing cataracts,a degenerative visionimpairing condition often needing surgery.The process of the reduction of glucose to sorbitol in the lens of...Purpose:Patients with diabetes mellitus have an elevated chance of developing cataracts,a degenerative visionimpairing condition often needing surgery.The process of the reduction of glucose to sorbitol in the lens of the human eye that causes cataracts is managed by the Aldose Reductase Enzyme(AR),and it is been found that AR inhibitors may mitigate the onset of diabetic cataracts.There exists a large pool of natural and synthetic AR inhibitors that can prevent diabetic complications,and the development of a machine-learning(ML)prediction model may bring new AR inhibitors with better characteristics into clinical use.Methods:Using known AR inhibitors and their chemical-physical descriptors we created the ML model for prediction of new AR inhibitors.The predicted inhibitors were tested by computational docking to the binding site of AR.Results:Using cross-validation in order to find the most accurate ML model,we ended with final cross-validation accuracy of 90%.Computational docking testing of the predicted inhibitors gave a high level of correlation between the ML prediction score and binding free energy.Conclusions:Currently known AR inhibitors are not used yet for patients for several reasons.We think that new predicted AR inhibitors have the potential to possess more favorable characteristics to be successfully implemented after clinical testing.Exploring new inhibitors can improve patient well-being and lower surgical complications all while decreasing long-term medical expenses.展开更多
Objective To identify the possible association between C（-106）T polymorphism of the aldose reductase （ALR） gene and diabetic retinopathy （DR） in a cohort of Chinese patients with type 2 diabetes mellitus （T2DM...Objective To identify the possible association between C（-106）T polymorphism of the aldose reductase （ALR） gene and diabetic retinopathy （DR） in a cohort of Chinese patients with type 2 diabetes mellitus （T2DM）. Methods From November 2009 to September 2010, patients with T2DM were recruited and assigned to DR group or diabetic without retinopathy （DWR） group according to the duration of diabetes and the grading of 7-field fundus color photographs of both eyes. Genotypes of the C（-106）T polymorphism （rs759853） in ALR gene were analyzed using the MassARRAY genotyping system and an association study was performed. Results A total of 268 T2DM patients （129 in the DR group and 139 in the DWR group） were included in this study. No statistically significant differences were observed between the 2 groups in the age of diabetes onset （P=0.10） and gender （P=0.78）. The success rate of genotyping for the study subjects was 99.6% （267/268）, with one case of failure in the DR group. The frequencies of the T allele in the C（-106）T polymorphism were 16.0% （41/256） in the DR group and 19.4% （54/278） in the DWR group （P=0.36）. There was no signit^cant difference in the C（-106）T genotypes between the 2 groups （P=0.40）. Compared with the wild-type genotype, odds ratio （OR） for the risk of DR was 0.7 （95% CI, 0.38-1.3） for the heterozygous CT genotype and 0.76 （95% CI, 0.18-3.25） for the homozygous TT genotype. The risk of DR was positively associated with microalbuminuria （OR=4.61; 95% CI, 2.34-9.05） and insulin therapy （OR=3.43; 95% CI, 1.94-6.09）. Conclusions Microalbuminuria and insulin therapy are associated with the risk of DR in Chinese patients with T2DM. C（-106）T polymorphism of the ALR gene may not be significantly associated with DR in Chinese patients with T2DM.展开更多
The extraction and solvent fi＇actionation of red alga Symphyocladia latiuscula, and repeated column chromatography led to isolation of 17 compounds： cholesterol （1）, 313,5β-dihydroxy-B-norcholestan-6βcarboxaldeh...The extraction and solvent fi＇actionation of red alga Symphyocladia latiuscula, and repeated column chromatography led to isolation of 17 compounds： cholesterol （1）, 313,5β-dihydroxy-B-norcholestan-6βcarboxaldehyde （2）, 6β-hydroxy-cholest-4-ene- 3-one （3）, 1-O-myristoyl-3-O-（6＇-sulfo-α-D-quinovopyranosyl）glycerol （4）, 1-O-palmitoyl-3-O-（6＇-sulfo-u-19-quinovopyranosyl） glycerol （5）, 1-O-palmitoyl-3-O-[α-D-galactopyranosyl（1→6）β-D-galactopyranosyl] glycerol （6）, 1-O-palmitoyl-3-O-β-D- galactopyranosylglycerol （7）, methyl hexadecanoate （8）, methyl stearate （9）, hexadecanoic acid （10）, γ-n-butyl cis-aconiate （11）, α-n-Butyl cis-aconiate （12）, phenethylamine （13）, 3,5-dibromo-L-tyrosine （14）, 3-methylbutylamine （15）, methyl pyroglutamate （16）, n-butyl pyroglutamate （17）. The structures of these compounds were identified by NMR spectroscopy and mass spectrometry, and compared with those reported in the literature. All the compounds were isolated from Symphyocladia genus for the first time. These compounds were investigated for their inhibitory effects on human recombinant aldose reductase in vitro. Of the compounds, 1-O-palmitoyl-3-O-β-D-galactopyranosylglycerol （7） demonstrated moderate enzyme inhibition.展开更多
To investigate the therapeutic potentials of na- tural sources, stepwise polarity fractions of Blumea balsamifera were tested for their ability to inhibit aldose reductase (AR) activity in rat lenses. Of these, the et...To investigate the therapeutic potentials of na- tural sources, stepwise polarity fractions of Blumea balsamifera were tested for their ability to inhibit aldose reductase (AR) activity in rat lenses. Of these, the ethyl acetate (EtOAc) fraction exhibited a unique AR inhibitory activity (IC50 value, 0.11 μg/mL). Apigenin was identified from the active EtOAc fraction and exhibited high AR inhibitory activity (IC50 value, 4.03 μM). The content of apigenin was measured in B. balsamifera (0.47 mg/g) by HPLC/UV analysis. Our result suggests that B. balsamifera could be a useful natural source for the development of a novel AR inhibitory agent against diabetic complications.展开更多
[Objectives] To explore whether there are natural substances that inhibit human aldose reductase in different extracts of Salvia deserta Schang.[Methods] The inhibitory activities of human aldose reductase from 28 ext...[Objectives] To explore whether there are natural substances that inhibit human aldose reductase in different extracts of Salvia deserta Schang.[Methods] The inhibitory activities of human aldose reductase from 28 extracts were screened.[Results] The methanol extract of roots of Salvia deserta Schang had the strongest inhibitory effect on human aldose reductase.[Conclusions] It was confirmed that Salvia deserta Schang has inhibitory effect on human aldose reductase.展开更多
Objective: To investigate the effects of different anesthesiaes on the activity of aldose reductase(AR) in RBC and the levels of plasma nitric oxide(NO) in patients undergoing gastric cancer operation. Methods: Twenty...Objective: To investigate the effects of different anesthesiaes on the activity of aldose reductase(AR) in RBC and the levels of plasma nitric oxide(NO) in patients undergoing gastric cancer operation. Methods: Twenty-eight patients undergoing gastric cancer operation were randomly divided into two groups with 14 cases for each. Anesthesia was maintained with 1.5-2.0MAC isoflurane plus epidural block in group Ⅱ. Venous blood samples were collected to measure the AR ctivity in RBC, the levels of plasma NO and glucose. Results: The plasma levels of glucose were increased significantly at 90 min after incision and kept at the high levels till the 1st postoperative day in group Ⅰ(P<0.01 or P<0.05) as compared with those before anesthesia, the changes in group Ⅱ were same as in group Ⅰ(P<0.01),but not on the 1st postoperative day. There was no significant difference between the two groups. The activity of AR in RBC was increased significantly and the level of plasma NO was decreased significantly on the 1st postoperative day in group Ⅰ(P<0.05). In group Ⅱ, AR and NO changed slightly,but these changes were not significant. The extent of change in the activity of AR or the level of NO no the 1st postoperative day in group Ⅱ was less than that in group Ⅰ(P<0.05). Conclusion: Polyol pathway in RBC activated under surgical hyperglycemia while the production of NO is inhibited in patients undergoing gastric cancer operation, which can be effectively attenuated by combined general-epidural anesthesia.展开更多
文摘Background Berberine is one of the main constituents of Coptidis rhizoma （CR） and Cortex phellodendri. In this study, we investigated the beneficial effects of berberine on renal function and its possible mechanisms in rats with diabetic nephropathy （DN）. Methods Male Wistar rats were divided into three groups： normal, diabetic model, and berberine treatment groups. Rats in the diabetic model and berberine treatment groups were induced to diabetes by intraperitonal injection with streptozotocin （STZ）. Glomerular area, glomerular volume, fasting blood glucose （FBG）, blood urea nitrogen （BUN）, serum creatinine （Cr） and urine protein for 24 hours （UP24h） were measured using commercially available kits. Meanwhile, the activity of superoxide dismutase （SOD）, content of malondialdehyde （MDA） in serum, activity of aldose reductase （AR） and the expression of AR mRNA and protein in kidney were detected by different methods. Results The results showed that oral administration of berberine （200 mg·kg^-1·d^-1） significantly ameliorated the ratio of kidney weight to body weight. Glomerular area, glomerular volume, FBG, BUN, Cr and UP24h were significantly decreased in the berberine treatment group compared with the diabetic model group （P〈0.05）. Berberine treatment significantly increased serum SOD activity and decreased the content of MDA compared with diabetic model group （P 〈0.05）. AR activity as well as the expression of AR mRNA and protein in the kidney was markedly decreased in the berberine treatment group compared with diabetic model group （P 〈0.05）. Conclusion These results suggested that berberine could ameliorate renal dysfunction in DN rats through controlling blood glucose, reduction of oxidative stress and inhibition of the activation of the polyol pathway.
基金supported by a grant from the National Natural Science Foundation of China,No.81060141
文摘Epalrestat is a noncompetitive and reversible aldose reductase inhibitor used for the treatment of diabetic neuropathy. This study assumed that epalrestat had a protective effect on diabetic peripheral nerve injury by suppressing the expression of aldose reductase in peripheral nerves of diabetes mellitus rats. The high-fat and high-carbohydrate model rats were established by intraperitoneal injection of streptozotocin. Peripheral neuropathy occurred in these rats after sustaining high blood glucose for 8 weeks. At 12 weeks after streptozotocin injection, rats were intragastrically administered epalrestat 100 mg/kg daily for 6 weeks. Transmission electron microscope revealed that the injuries to myelinated nerve fibers, non-myelinated nerve fibers and Schwann cells of rat sciatic nerves had reduced compared to rats without epalrestat administuation. Western blot assay and immunohistochemical results demonstrated that after intervention with epalrestat, the activities of antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase gradually increased, but aldose reductase protein expression gradually diminished. Results confirmed that epalrestat could protect against diabetic peripheral neuropathy by relieving oxidative stress and suppressing the polyol pathway.
基金supported by the National Natural Science Foundation of China,No.81370165a grant from the Public Benefit Technology and Society Development Program of Zhejiang Province of China,No.2015C33309+2 种基金a grant from the Ningbo Science and Technology Innovation Team Program in China,No.2014B82002,2015B11050a grant from the Ningbo Science and Technology Project in China,No.2015A610217the Fang Runhua Fund of Hong Kong,K.C.Wong Magna Fund in Ningbo University
文摘OBJECTIVE： To evaluate the efficacy of α-lipoic acid（ALA） plus epalrestat combination therapy in the treatment of diabetic peripheral neuropathy（DPN）. DATA SOURCES： The electronic databases of Pub Med, Medline, Embase, the Cochrane Library, the Chinese National Knowledge Infrastructure, the Wanfang Database and the Chinese Biomedical Database were used to retrieve relevant studies without language restrictions. The search was conducted from the inception of each database to 7 October 2016. The key terms were（diabetic peripheral neuropathy or diabetic neuropathy or DPN） AND（α-lipoic acid or lipoic acid or thioctic acid） AND epalrestat. DATA SELECTION： All of the eligible studies met the following inclusion criteria：（1） Randomized controlled trials that compared efficacy and safety of epalrestat plus ALA combination therapy versus epalrestat or ALA monotherapy in patients with DPN.（2） The minimum duration of treatment was 2 weeks.（3） The DPN patients were diagnosed using the World Health Organization standardized type 2 diabetes mellitus and DPN criteria.（4） Studies contained at least one measure that could reflect the efficacy of the drug and nerve conduction velocities. Studies in which the control group used epalrestat or ALA combined with other drugs were excluded. Statistical analyses were performed using STATA software for meta-analysis. OUTCOME MEASURES： The primary outcomes were the therapeutic efficacy, median motor nerve conduction velocity（MNCV）, median sensory nerve conduction velocity（SNCV）, peroneal MNCV and peroneal SNCV.RESULTS： Twenty studies with 1894 DPN patients were included, including 864 patients in the ALA plus epalrestat group, 473 in the ALA group and 557 in the epalrestat group. The efficacy of ALA plus epalrestat combination therapy was superior to ALA and epalrestat monotherapies（RR = 1.29, 95% CI： 1.21–1.38; RR = 1.43, 95% CI： 1.34–1.54, respectively）. ALA plus epalrestat combination therapy also significantly improved m
文摘Diabetes mellitus is not a single disease but is a group of metabolic disorders affecting a huge numlier of population in the world.It is mainly characterized by chronic hyperglycemia,resulting from defects in insulin secretion or insulin action.It is predicated that the number of diabetes person in the world could reach upto 366 million by the year 2030.Even though the cases of diabetes are increasing day by day,except insulin and oral hypoglycemic drugs no other way of treatment has been successfully developed so far.Thus,the objective of the present review is to provide an insight over the pathophysiological and etiological aspects of diabetes mellitus along with the remedies available for this metabolic disorder.The review also contains brief idea about diabetes mellitus and the experimental screening model with their relevant mechanism and significance mainly used nowadays.Alloxan and streptozotocin are mainly used for evaluating the antidiabetic activity of a particular drug.This review contain list of medicinal plants which have been tested for their antidiabetic activity in the alloxan induced diabetic rat model.From the available data in the literature,it was found that plant having antidiabetic activity is mainly due to the presence of the secondary metabolite.Thus,the information provided in this review will help the researchers for the development of an alternative methods rather than insidin and oral hypoglycemic agents for the treatment of diabetes niellitus,which will minimize the complication associated with the diabetes and related disorder.
基金Supported by the Basic Research Program of the Korea Science & Engineering Foundation (No. 2009-0068732)the Basic Research Program of the National Research Foundation of Korea (No.2011-0020163)+1 种基金the Bio-Industry Technology Development Program funded by the Korea Institute of Planning & Evaluation for Technology in Food, Agriculture Forestry & Fisheries (No.112005-3)the BK21 Program and by the MRC program of KRF (R13-2005-012-01001-1)
文摘AIM: To study the contribution of tonicity response element binding protein(Ton EBP) in retinal ganglion cell(RGC) death of diabetic retinopathy(DR).METHODS: Diabetes was induced in C57BL/6 mice by five consecutive intraperitoneal injections of 55 mg/kg streptozotocin(STZ). Control mice received vehicle(phosphate-buffered saline). All mice were killed 2mo after injections, and the extent of cell death and the protein expression levels of Ton EBP and aldose reductase(AR) were examined.RESULTS: The Ton EBP and AR protein levels and the death of RGC were significantly increased in the retinas of diabetic mice compared with controls 2mo after the induction of diabetes. Terminal deoxynucleotidyl transferase(Td T)-mediated d UTP nick end labeling(TUNEL)-positive signals co-localized with Ton EBP immunoreactive RGC. These changes were increased in the diabetic retinas compared with controls.CONCLUSION: The present data show that AR and Ton EBP are upregulated in the DR and Ton EBP may contribute to apoptosis of RGC in the DR.
基金supported by University Grants Commission,New Delhi(grant No.IT/DEV/08-09/3252/L)
文摘Objective:To evaluate the aldose reductase inhibitory(ARI)activity of different fractions of Hybanthus enneaspermus for potential use in diabetic cataract.Methods:Total phenol and flavonoid content of different fractions was determined.ARI activity of different fractions in rat lens was investigated in vitro.Results:The results showed significant level of phenolic and flavonoid content in ethyl acetate fraction[total phenol(212.15±0.79 mg/g),total flavonoid(39.11±2.27mg/g)]and aqueous fraction[total phenol(140.62±0.57mg/g),total flavonoid(26.07±1.49 mg/g)]as compared with the chloroform fraction[total phenol(68.56±0.51mg/g),total flavonoid(13.41±0.82mg/g)]and petrolium ether fraction[total phenol(36.68±0.43mg/g),total flavonoid(11.55±1.06mg/g)].There was a significant difference in the ARI activity of each fraction,and it was found to be the highest in ethyl acetate fraction[IC_(50)(49.26±1.76μg/mL)]followed by aqueous extract[IC_(50)(70.83±2.82μg/mL)]and it was least in the petroleum ether fraction[IC_(50)(118.89±0.71μg/mL)].Chloroform fraction showed moderate activity[IC_(50)(98.52±1.80μg/mL)].Conclusions:Different fractions showed significanct amount of ARI activity,where in ethyl acetate fraction it was found to be maximum which may be due to its high phenolic and flavonoid content.The extract after further evaluation may be used in the treatment of diabetic cataract.
文摘Objective:To assesse the inhibitor) effect of alcoholic extract of two Indian medicinal plants namely Ceasalpinia digyna Rottler and.Alangium lamarckii Thwaits on aldose reductase（AR） of rat lens.Methods:Rats lens were enucleated through posterior approach and their homogenate was prepared and centrifuged to obtain a clear supernatant for the determination of AR activity and protein content.Results:The alcoholic extract of Ceasalpirda digyna and Alangium lamarckii had a potent inhibitory effect on the lens AR enzyme.The IC<sub>50</sub> values of alcoholic extract of the selected plants were calculated and were（46.29±11.17） and（106.00±5.11）μg/mL,respectively. Quercetin was used as a positive control and its IC<sub>50</sub> value was（2.95±1.53）μg/mL.Conclusions:Thus,it is concluded that alcoholic extracts of the selected plant exhibit significant inhibitory effects on AR in the rat lens in vitro.
文摘为分析配料(硫化物、糖)组成对高温芝麻饼粕蛋白酶解物(High temperature sesame cake protein hydrolysate,HTSPH)制备肉味香精的影响,首先固定木糖与HTSPH含量,考察5种硫化物如半胱氨酸(LCys)、甲硫氨酸(L-Met)、硫胺素(VB1)对美拉德反应产物(Maillard reaction products,MRPs)的感官特性、挥发性成分、pH、褐变与糖基化程度的影响,随后对比木糖、核糖、半乳糖等9种糖与L-Cys、HTSPH反应得到MRPs的特性差异,最后,混料试验考察L-Cys、木糖、HTSPH三者组成对MRPs感官特性与挥发性成分影响。结果显示,不同硫化物形成MRPs的挥发性成分组成差异明显,L-Cys的MRPs肉味突出,感官评价得分最高(69.32±1.34)。对比不同糖的MRPs的性质组成发现,戊糖的MRPs中感官评价得分显著高于已糖的MRPs,其挥发性成分中富含肉香味成分,木糖是适宜由HTSPH制作肉味香精的糖类。混料试验表明L-Cys、木糖与HTSPH组成会显著影响MRPs风味特征。偏最小二乘回归分析发现22种关键挥发性成分。5-甲基-2-噻吩甲醛、二糠基二硫醚、5-乙基噻吩-2-甲醛、4,6-二甲基-1H,3H-噻吩并[3,4-c]噻吩、苯甲醛、2-糠基2-甲基-3-呋喃基二硫化物、2-糠硫醇与感官得分正相关。本研究为高温芝麻饼粕制备肉味香精提供理论指导。
基金supported by grants from the National Natural Science Foundation of China(31991193 and 32230025)the National Key R&D Program of China(2021YFA1101001).
文摘Carbohydrate metabolism disorders(CMDs),such as diabetes,galactosemia,and mannosidosis,cause ciliopathy-like multiorgan defects.However,the mechanistic link of cilia to CMD complications is still poorly understood.Herein,we describe significant cilium disassembly upon treatment of cells with pathologically relevant aldoses rather than the corresponding sugar alcohols.Moreover,environmental aldehydes are able to trigger cilium disassembly by the steric hindrance effect of their formyl groups.Mechanistic studies reveal that aldehydes stimulate extracellular calcium influx across the plasma membrane,which subsequently activates the calmodulin-Aurora A-histone deacetylase 6 pathway to deacetylate axonemal microtubules and triggers cilium disassembly.In vivo experiments further show that Hdac6 knockout mice are resistant to aldehyde-induced disassembly of tracheal cilia and sperm flagella.These findings reveal a previously unrecognized role for formyl group-mediated cilium disassembly in the complications of CMDs.
基金financially supported by the National Natural Science Foundation of China(No.81373952)the Innovation Method Fund of China(No.2012IM030600)
文摘The formation of advanced glycation end-products （AGEs） and aldose reductase （AR） activity have been implicated in the development of diabetic complications. Our study sought to characterize the capacities of eleven herbal extracts against the formation of AGEs and the AR activity. An ultrahigh performance liquid chromatography and tandem mass spectrometry （UPLC-MS/MS） method was used for the detection of AR activity and the screening of AR inhibitors in this research. The amount of sorbitol from each analyte was directly detected using the multiple reaction monitoring mode and the sorbitol level could be reduced via the addition of an inhibitor. Moreover, the BSA/glucose （fructose） system was applied to investigate their inhibitory activities of AGEs formation in glycation model reactions. Compared with other screened herbs used in our study, Flos Sophorae lrnrnaturus and Radix Scutellariae seemed to be more effective on inhibiting the formation of AGEs and AR activity. The inhibiting capacities of herbal extracts against AR activity and AGEs formation may be correlated with the bioactive components of the herbal extracts. The differences were correlated with the amount of polyphenol and flavonoid components. In the study, we have investigated the potential anti-hyperglycemic bioactivity of eleven herbal extracts in vitro, which could provide a reference for further in vivo research in the prevention and treatment of diabetic complications.
基金supported by Jiangsu Province Department of health Fund(No.H200705)
文摘Objective： To compare the effects of different methods of anesthesia and analgesia on the activities of phosphofructokinase（PFK）, glucose-6-phosphate dehydrogenase（G-6PD） and aldose reductase（AR） in erythrocytes and levels of plasma glucose and stress hormones in patients undergoing esophagus surgery. Methods： Sixty-two patients scheduled for esophagus surgery were randomly divided into three groups： group Ⅰ （n = 20） receiving only general anesthesia（GA） followed by intravenous patient controlled analgesia（PCA） with fentanyl 15 μg/kg. The other two groups receiving both general anesthesia combined with thoracic epidural anesthesia （GEA） and either intravenous PCA with fentanyl 15 μg/kg （group Ⅱ, n = 21） or thoracic epidural analgesia（TEA） with 0.125% ropivacaine and 0.0002% fentanyl mixture（group Ⅲ, n = 21） after the operation. Venous blood samples were collected for measurements of PFK, G-rPD and AR activities in erythrocytes and plasma glucose, cortisol, epinephrine and norepinephrine before induction （T1）, 60 min following the incision （T2）, 60 min（T3） after operation, on the lst（T4） and 2nd postoperative day（T5）. Results： The activities of PFK decreased（P 〈 0.01 or P = 0.004） and the activities of G-6PD and AR increased（P 〈 0.01） in groups Ⅰ and Ⅱ on T4 compared with those on T1 Between the two groups, the activities of these enzymes in group Ⅱ changed less than those of group Ⅰ （P 〈 0.01 or P 〈 0.05）. These enzymes activities changed slightly in group Ⅲ on T4（P 〉 0.05）. There were significant differences between group Ⅲand the other two groups（P 〈 0.0l or P 〈 0.05）. The levels of plasma glucose increased significantly on T2（P 〈 0.01）, reached peak values on Ta（P 〈 0.01） and fell on T5 in the three groups. Compared to those of groups Ⅰ and Ⅱ, the values of plasma glucose in group Ⅲwere lower on T4 and T5（P 〈 0.05 or P 〈 0.01）. The cortisol concentration in each gr
基金supported by the National Development of Key Novel Drugs for Special Projects of China(No.2017ZX09304014)the National Natural Science Foundation of China(No.82003929)+1 种基金Hunan Provincial Natural Science Foundation of China(No.2021JJ40993)Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples(No.2017TP1037).
文摘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-AMPKαlevels 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.
基金Supported by Hubei Province Natural Science Fund( 99J0 5 6 )
文摘A series of Benzisolselenazolone (BISA) derivatives were synthesized and evaluated for their antibacterial activities againstE coli. by using LKB-2277 bioactivity monitor. Other bioactivities were tested by the method of High Throughput Screening for pharmaceutical activity compounds (HTP) BISA derivatives 3b, at the concentration of 40 μg/mL, showed 100%antibacterial activity and 62%inhibition rate of aldose reductase (at the concentration of 5μg/mL). These new compound structures have determined by IR,1H NMR and MS spectra.
文摘AIM:To investigate the aldose reductase(AR)inhibition capacity of astragalin(AST)against streptozoticin-induced diabetic cataracts(DCs)in rats.METHODS:Ex vivo investigations were conducted by treating the lens of a goat placed for 72h in artificial aqueous humor(AAH)of pH 7.8 at room temperature with cataract-causing substance(55 mmol/L of galactose)and in vivo studies were performed on rats via induction with streptozotocin.AST was administered at different dose levels and scrutinize for DC activity.RESULTS:In diabetic rats,AST improved the body weight,blood insulin,and glucose as well as the levels of galactitol in a dose-dependent way,other biochemical parameters i.e.inflammatory mediators and cytokines,and also suppress AR activity.The level of the antioxidant parameters such as superoxide dismutase(SOD),catalase(CAT),and glutathione(GSH)activity were also altered on a diabetic lens after the administration of the AST.CONCLUSION:AST protects against lens opacification to avoid cataracts and polyols formation,indicating that it could be used as a potential therapeutic agent for diabetes.
文摘Purpose:Patients with diabetes mellitus have an elevated chance of developing cataracts,a degenerative visionimpairing condition often needing surgery.The process of the reduction of glucose to sorbitol in the lens of the human eye that causes cataracts is managed by the Aldose Reductase Enzyme(AR),and it is been found that AR inhibitors may mitigate the onset of diabetic cataracts.There exists a large pool of natural and synthetic AR inhibitors that can prevent diabetic complications,and the development of a machine-learning(ML)prediction model may bring new AR inhibitors with better characteristics into clinical use.Methods:Using known AR inhibitors and their chemical-physical descriptors we created the ML model for prediction of new AR inhibitors.The predicted inhibitors were tested by computational docking to the binding site of AR.Results:Using cross-validation in order to find the most accurate ML model,we ended with final cross-validation accuracy of 90%.Computational docking testing of the predicted inhibitors gave a high level of correlation between the ML prediction score and binding free energy.Conclusions:Currently known AR inhibitors are not used yet for patients for several reasons.We think that new predicted AR inhibitors have the potential to possess more favorable characteristics to be successfully implemented after clinical testing.Exploring new inhibitors can improve patient well-being and lower surgical complications all while decreasing long-term medical expenses.
基金Supported by the National Basic Research Program of China(973 Program,2007CB512201)the Beijing Municipal Health Bureau Grant(2009208)the Beijing Natural Science Foundation(7131007)
文摘Objective To identify the possible association between C（-106）T polymorphism of the aldose reductase （ALR） gene and diabetic retinopathy （DR） in a cohort of Chinese patients with type 2 diabetes mellitus （T2DM）. Methods From November 2009 to September 2010, patients with T2DM were recruited and assigned to DR group or diabetic without retinopathy （DWR） group according to the duration of diabetes and the grading of 7-field fundus color photographs of both eyes. Genotypes of the C（-106）T polymorphism （rs759853） in ALR gene were analyzed using the MassARRAY genotyping system and an association study was performed. Results A total of 268 T2DM patients （129 in the DR group and 139 in the DWR group） were included in this study. No statistically significant differences were observed between the 2 groups in the age of diabetes onset （P=0.10） and gender （P=0.78）. The success rate of genotyping for the study subjects was 99.6% （267/268）, with one case of failure in the DR group. The frequencies of the T allele in the C（-106）T polymorphism were 16.0% （41/256） in the DR group and 19.4% （54/278） in the DWR group （P=0.36）. There was no signit^cant difference in the C（-106）T genotypes between the 2 groups （P=0.40）. Compared with the wild-type genotype, odds ratio （OR） for the risk of DR was 0.7 （95% CI, 0.38-1.3） for the heterozygous CT genotype and 0.76 （95% CI, 0.18-3.25） for the homozygous TT genotype. The risk of DR was positively associated with microalbuminuria （OR=4.61; 95% CI, 2.34-9.05） and insulin therapy （OR=3.43; 95% CI, 1.94-6.09）. Conclusions Microalbuminuria and insulin therapy are associated with the risk of DR in Chinese patients with T2DM. C（-106）T polymorphism of the ALR gene may not be significantly associated with DR in Chinese patients with T2DM.
基金National Natural Sciences Foundation of China(Grant No.30672599)
文摘The extraction and solvent fi＇actionation of red alga Symphyocladia latiuscula, and repeated column chromatography led to isolation of 17 compounds： cholesterol （1）, 313,5β-dihydroxy-B-norcholestan-6βcarboxaldehyde （2）, 6β-hydroxy-cholest-4-ene- 3-one （3）, 1-O-myristoyl-3-O-（6＇-sulfo-α-D-quinovopyranosyl）glycerol （4）, 1-O-palmitoyl-3-O-（6＇-sulfo-u-19-quinovopyranosyl） glycerol （5）, 1-O-palmitoyl-3-O-[α-D-galactopyranosyl（1→6）β-D-galactopyranosyl] glycerol （6）, 1-O-palmitoyl-3-O-β-D- galactopyranosylglycerol （7）, methyl hexadecanoate （8）, methyl stearate （9）, hexadecanoic acid （10）, γ-n-butyl cis-aconiate （11）, α-n-Butyl cis-aconiate （12）, phenethylamine （13）, 3,5-dibromo-L-tyrosine （14）, 3-methylbutylamine （15）, methyl pyroglutamate （16）, n-butyl pyroglutamate （17）. The structures of these compounds were identified by NMR spectroscopy and mass spectrometry, and compared with those reported in the literature. All the compounds were isolated from Symphyocladia genus for the first time. These compounds were investigated for their inhibitory effects on human recombinant aldose reductase in vitro. Of the compounds, 1-O-palmitoyl-3-O-β-D-galactopyranosylglycerol （7） demonstrated moderate enzyme inhibition.
文摘To investigate the therapeutic potentials of na- tural sources, stepwise polarity fractions of Blumea balsamifera were tested for their ability to inhibit aldose reductase (AR) activity in rat lenses. Of these, the ethyl acetate (EtOAc) fraction exhibited a unique AR inhibitory activity (IC50 value, 0.11 μg/mL). Apigenin was identified from the active EtOAc fraction and exhibited high AR inhibitory activity (IC50 value, 4.03 μM). The content of apigenin was measured in B. balsamifera (0.47 mg/g) by HPLC/UV analysis. Our result suggests that B. balsamifera could be a useful natural source for the development of a novel AR inhibitory agent against diabetic complications.
基金Supported by Scientific Research Program of Universities in Xinjiang Uygur Autonomous Region(XJEDU2018Y025)
文摘[Objectives] To explore whether there are natural substances that inhibit human aldose reductase in different extracts of Salvia deserta Schang.[Methods] The inhibitory activities of human aldose reductase from 28 extracts were screened.[Results] The methanol extract of roots of Salvia deserta Schang had the strongest inhibitory effect on human aldose reductase.[Conclusions] It was confirmed that Salvia deserta Schang has inhibitory effect on human aldose reductase.
基金Science Foundation of Jiangsu Province govenment(BJ97003)
文摘Objective: To investigate the effects of different anesthesiaes on the activity of aldose reductase(AR) in RBC and the levels of plasma nitric oxide(NO) in patients undergoing gastric cancer operation. Methods: Twenty-eight patients undergoing gastric cancer operation were randomly divided into two groups with 14 cases for each. Anesthesia was maintained with 1.5-2.0MAC isoflurane plus epidural block in group Ⅱ. Venous blood samples were collected to measure the AR ctivity in RBC, the levels of plasma NO and glucose. Results: The plasma levels of glucose were increased significantly at 90 min after incision and kept at the high levels till the 1st postoperative day in group Ⅰ(P<0.01 or P<0.05) as compared with those before anesthesia, the changes in group Ⅱ were same as in group Ⅰ(P<0.01),but not on the 1st postoperative day. There was no significant difference between the two groups. The activity of AR in RBC was increased significantly and the level of plasma NO was decreased significantly on the 1st postoperative day in group Ⅰ(P<0.05). In group Ⅱ, AR and NO changed slightly,but these changes were not significant. The extent of change in the activity of AR or the level of NO no the 1st postoperative day in group Ⅱ was less than that in group Ⅰ(P<0.05). Conclusion: Polyol pathway in RBC activated under surgical hyperglycemia while the production of NO is inhibited in patients undergoing gastric cancer operation, which can be effectively attenuated by combined general-epidural anesthesia.
