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.
Aldehyde Reductase* ; Alkaloids* ; Corydalis* ; Diabetes Complications ; Humans ; Methanol

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.
Aldehyde Reductase* ; Animals ; Cataract ; Diet ; Epithelium ; Galactose ; Membranes ; Models, Animal ; Rats* ; Rats, Sprague-Dawley ; Rupture

The intracellular accumulation of sorbitol, a product, which arises from polyol pathway: one of glucose metabolic pathways, has been said to be one of the pathogens for diabetic retinopathy. So, to obtain fundamental data regarding the time of administratin as well as the dosage of aldose reductase inhibitor(ARI) which inhibits the formation of sorbitol, we examined the interrelationship between RBC-sorbitol and glucose, HbAlc, and the association of RBC-Sorbitol with the severity of diabetic retinopathy in fifty NIDDM patients(20 No diabetic retinopathy, 10 mild NPDR, 10 sever NPDR, 10 PDR). In results, there was no association between RBC-sorbitol and glucose(r=0.172), between RBC-sorbitol and HbAlC(r=0.262), also there was no discernible RBC-Sorbitol level in each degree of diabetic retinopathic severity (F`=0.67, p>0.05), and wide variation of RBC-sorbitol level in each diabetic patients. Thus, for the progression of diabetic retinopathy, the duration time of high sorbitol level was predicted to be of more important value than the sorbitol level at the time of diagnosis. Therefore, we have shown through the research that ARI needs to be administered early on when RBC-Sorbitol level is higher than normal and in terms of ARI dosage, administering differenct ARI dosage according to different sorbitol level of each patient will be more effective for prevention and treatment of diabetic retinopathy.
Aldehyde Reductase ; Diabetes Mellitus, Type 2 ; Diabetic Retinopathy* ; Diagnosis ; Glucose ; Humans ; Metabolic Networks and Pathways ; Sorbitol

OBJECTIVETo synthesize epalrestat and to improve the method of synthesis.

METHODSGlycine reacted with carbondisulfide,then with ClCH(2)COONa to give 3-carboxymethylrhodanine. PhCHO reacted with CH(3)CH(2)CHO in NaOH/EtOH solution to produce 2-methylcinnamaldehyde.3-carboxymethylrhodanine and 2-methylcinnamaldehyde were treated with NH(3).H(2)O to obtain epalrestat.

RESULTThe described method was effective in synthesis of Epalrestat and the yield was higher than that of in references.

CONCLUSIONThe results suggest that this method is suitable for industrial production.

Hypertonicity imposes a great deal of stress to cells since it causes rise in cellular ionic strength, which can be reduced by the accumulation of compatible osmolytes. TonEBP plays a central role in the cellular accumulation of compatible osmolytes via transcriptional stimulation of membrane transporters and aldose reductase. Alternatively spliced forms of TonEBP mRNA have previously been reported and two of them showed different transcriptional activity. In the present study, isoform-specific antibodies were produced to confirm the translation of the spliced mRNA to protein. TonEBP was immunoprecipitated by using anti-TonEBP antibody and then immunoblotted using anti-TonEBP or isoform specific antibodies to find out the expression profile of TonEBP isoforms in basal or stimulated condition. From these results, we conclude that all TonEBP isoforms are expressed in mammalian cells and their expression patterns are not same in every cells.
Aldehyde Reductase ; Alternative Splicing ; Antibodies ; Membrane Transport Proteins ; Osmolar Concentration ; Protein Isoforms* ; RNA, Messenger

OBJECTIVETo explore the biological function and possible underlying mechanism of aldo-keto reductase family 1 member B10 (AKR1B10) gene during hepatocarcinogenesis.

METHODSA pair of chemically synthesized small interfering RNA (siRNA) targeting on AKR1B10 was transfected into liver cancer cell line MHCC97H by LipofectamineTM 2000. After confirming the interfering effects of AKR1B10-siRNAs through Quant SYBR Green polymerase chain reaction (Real-time PCR), Western blot and enzymatic activity assay, the capabilities of proliferation and apoptosis of the transfected cells were observed by CCK-8 assay and flow cytometry analysis, and the expressions of a group of tumor-related gene such as c-myc, c-fos, N-ras were observed through Real-time PCR.

RESULTSThe expressions of AKR1B10 and the enzymatic activity were down-regulated significantly in AKR1B10-siRNA-transfected cells. Compared with mock and blank control groups, cell growth in AKR1B10-siRNA-transfected group was inhibited by 26.6%+/-3.1% at 72h after transfection. The ratio of apoptotic cells was 37.3%+/-1.0% in AKR1B10-siRNA-transfected group, which was significantly higher than that in mock and blank control groups (P < 0.01). Real-time PCR showed that the expressions of oncogene c-myc, c-fos and N-ras, and the proliferation-associated gene ki-67 were down-regulated in AKR1B10-siRNA-transfected cells, while the expressions of apoptosis-promoting gene caspas-3 and bax were up-regulated.

CONCLUSIONSAKR1B10 might promote proliferation, inhibit apoptosis and then induce malignant transformation of hepatocytes by regulating the expression level of some tumor-related genes.

OBJECTIVE: To screen for differentially expressed circular RNAs (circRNAs) in the serum of preterm infants with intraventricular hemorrhage (IVH) and explore the competitive endogenous RNA (ceRNA) mechanism of circRNAs in IVH in these infants. METHODS: Fifty preterm infants (gestational age of 28 to 34 weeks) admitted in our department between January, 2019 and January, 2020 were enrolled in this study, including 25 with a MRI diagnosis of IVH and 25 without IVH. Serum samples were collected from 3 randomly selected infants from each group for profiling differentially expressed circRNAs using circRNA array technique. Gene ontology (GO) and pathway analyses were performed to reveal the function of the identified circRNAs. The circRNA-miRNA-mRNA network was constructed to identify the co-expression network of hsa_circ_ 0087893. RESULTS: A total of 121 differentially expressed circRNAs were identified in the infants with IVH, including 62 up-regulated and 59 down-regulated circRNAs. GO and pathway analyses showed that these circRNAs were involved in multiple biological processes and pathways, including cell proliferation, activation and death, DNA damage and repair, retinol metabolism, sphingolipid metabolism, cell adhesion molecules. Among these circRNAs, hsa_circ_0087893 was found to have significant down-regulation in IVH group and co-express with 41 miRNAs and 15 mRNAs (such as miR-214-3p, miR-761, miR-183-5p, AKR1B1, KRT34, PPP2CB, and HPRT1). CONCLUSION The circRNA hsa_circ_0087893 may function as a ceRNA and play an important role in the occurrence and progression of IVH in preterm infants.
Infant, Newborn ; Infant ; Humans ; RNA, Circular ; Infant, Premature ; MicroRNAs ; RNA, Messenger ; Cerebral Hemorrhage/genetics* ; Aldehyde Reductase

Antioxidative and aldose reductase (AR)-inhibitory effects of a fermentation filtrate of Rubus coreanus (FRC) were investigated using corneal/retinal homogenate and lens cytosol, respectively. Rat corneal/retinal homogenate was treated with 50 microM FeCl3 in the presence of FRC (3.2-100 microg/mL) for 30 min at 37degrees C, and thiobarbituric acid-reactive substances (TBARS) was quantified as a lipid peroxidation parameter. FRC markedly suppressed the TBARS production in a concentration-dependent manner, leading to 50% (IC50) and 100% (IC100) inhibitory concentrations of 20 and 95 microg/mL, respectively, which was similar to the effect of butylated hydroxyanisole. Activity of AR from rat lens was assayed in the presence of FRC (1-31.6 microg/mL) at 25degrees C using glyceraldehyde as a substrate. FRC inhibited lens AR by 50% (IC50) and 90% (IC90) at approximately 2 and 31.6 microg/mL, respectively, comparable to the effect of quercetin. The results indicate that ERC could be a promising candidate for the improvement of eye injury and visual dysfunction of dry eye and diabetic patients.
Aldehyde Reductase ; Animals ; Butylated Hydroxyanisole ; Cytosol ; Eye ; Eye Injuries ; Fermentation ; Glyceraldehyde ; Humans ; Lipid Peroxidation ; Quercetin ; Rats ; Thiobarbituric Acid Reactive Substances

Tonicity-responsive enhancer binding protein (TonEBP) is a signal transcription factor of transporters such as sodium-myo-inositol cotransporter (SMIT), aldose reductase. TonEBP has a variety of functions such as control of intracellular osmolytes and immunomodulating. It is known that TonEBP is abundant in the placenta, but location and function aren't known. The aim of this study is to describe the localization of TonEBP in the placenta. We assayed the immunohistochemistry of TonEBP and performed in situ hybridization of SMIT in normal human full term placenta. In normal human full term placenta, TonEBP was in villous trophoblasts, extravillous trophoblasts and some endothelial cells. The result of the in situ hybridization of SMIT was similar to that of immunohistochemistry of TonEBP. Neither TonEBP nor SMIT was present in TonEBP knockout mouse placenta. This shows TonEBP is a key factor in SMIT transcription. TonEBP may play an important role in transporting of inositol to fetus in placenta.
Aldehyde Reductase ; Animals ; Carrier Proteins ; Endothelial Cells ; Fetus ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Inositol ; Mice ; Mice, Knockout ; Placenta ; Transcription Factors ; Trophoblasts

Oxidative stress and methylglyoxal (MG), a reactive dicarbonyl metabolites produced by enzymatic and non-enzymatic reaction of normal metabolism, induced aldose reductase (AR) expression in rat aortic smooth muscle cells (SMC). AR expression was induced in a time-dependent manner and reached at a maximum of 4.5-fold in 12 h of MG treatment. This effect of MG was completely abolished by cyclohemide and actinomycin D treatment suggesting AR was synthesized by de novo pathway. Pretreatment of the SMC with N-acetyl-L-cysteine significantly down-regulated the MG-induced AR mRNA. Furthermore, DL-Buthionine-(S,R)-sulfoximine, a reagent which depletes intracellular glutathione levels, increased the levels of MG-induced AR mRNA. These results indicated that MG induces AR mRNA by increasing the intracellular peroxide levels. Aminoguanidine, a scanvenger of dicarbonyl, significantly down-regulated the MG-induced AR mRNA. In addition, the inhibition of AR activities with statil, an AR inhibitor, enhanced the cytotoxic effect of MG on SMC under normal glucose, suggesting a protective role of AR against MG-induced cell damages. These results imply that the induction of AR by MG may contribute to an important cellular detoxification of reactive aldehyde compounds generated under oxidative stress in extrahepatic tissues.
Acetylcysteine ; Aldehyde Reductase* ; Animals ; Dactinomycin ; Glucose ; Glutathione ; Metabolism ; Muscle, Smooth, Vascular* ; Myocytes, Smooth Muscle ; Oxidative Stress* ; Pyruvaldehyde ; Rats ; RNA, Messenger