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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 .
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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.
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Background Sugar cataract is one of the major diabetic complications in the eye,but there is not effective medicine to prevent or delay development of cataract. Objective The goal of this study was to investigate the effects and the potential mechanism of aldose reductase (AR) inhibitor,AL-1576 on prevention of galactose cataract in rats. Methods Forty-two SD rats were randomly and equally divided into 7 groups.The cataracts were induced by feeding with 50％ galactose.At the day of feeding galactose and the day 5,10 and 15 after feeding galactose,AL-1576 was added into the feeds.The rats were divided AL-1576 prevention group and early-,intermediate-or late-stage intervention groups.For another group,the withdrawing AL-1576 group,AL-1576 was added into the feeds at the day of feeding galactose,then was removed after 10 days.The lenses of the rats were examined under the slit-lamp microscope before and after given AL-1576 every 5 days.At the day 35,the lenses were obtained.The wet and dry weight of the lenses were weighted,respectically,to calculate the water content of the lenses.Activities of AR and superoxidedismutase (SOD) and contents of glutathione (GSH) of the lenses were measured by their commercial detecting kits.The care and use of the animals complied with the Regulations for the Administration of Affairs Concerning Experimental Animals by State Science and Technology Commission. Results In AL-1576 prevention group,all lenses maintained clear.Opacification of the lenses were significantly attenuated in all three AL-1576 intervention groups and withdrawing AL-1576 group compared with the cataractous model group ( P＜0.05),but the inhibiting role was weaken with late intervention.The water contents and the activities of AR of the lenses were decreased,the contents of SOD and GSH were dramatically increased in all different AL-1576 treated groups compared with the cataractous model group (P＜0.05).Moreover,AL-1576 prevention group showed the best effect on all indexes (P＜0.05). Conclusions The activity of AR can be inhibited by AL-1576 at the different stages of development of cataract induced by galactose.By blocking and attenuating formation of the edema and elevating antioxdative capacity in the lenses,AL-1576 prevents and delays the formation of galactose cataract.
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PURPOSE: The vascular endothelial growth factor (VEGF) expression of podocyte is one of the well-known major factors in development of diabetic nephropathy. In this study, we investigated the effects of aldose reductase inhibitor, fidarestat on diabetic nephropathy, and renal VEGF expression in a type 1 diabetic rat model. MATERIALS AND METHODS: Twenty four Sprague-Dawley male rats which were performed intraperitoneal injection of streptozotocin and normal six rats were divided into four groups including a normal control group, untreated diabetic control group, aldose reductase (AR) inhibitor (fidarestat, 16 mg.kg(-1).day(-1)) treated diabetic group, and angiotensin receptor blocker (losartan, 20 mg.kg(-1).day(-1)) treated diabetic group. We checked body weights and blood glucose levels monthly and measured urine albumin-creatinine ratio (ACR) at 8 and 32 weeks. We extracted the kidney to examine the renal morphology and VEGF expressions. RESULTS: The ACR decreased in fidarestat and losartan treated diabetic rat groups than in untreated diabetic group (24.79 +/- 11.12, 16.11 +/- 9.95, and 84.85 +/- 91.19, p < 0.05). The renal VEGF messenger RNA (mRNA) and protein expression were significantly decreased in the fidarestat and losartan treated diabetic rat groups than in the diabetic control group. CONCLUSION: We suggested that aldose reductase inhibitor may have preventive effect on diabetic nephropathy by reducing renal VEGF overexpression.
Subject(s)
Animals , Male , Rats , Aldehyde Reductase/antagonists & inhibitors , Antihypertensive Agents/therapeutic use , Diabetes Mellitus, Experimental/drug therapy , Diabetic Nephropathies/prevention & control , Imidazolidines/therapeutic use , Kidney/drug effects , Losartan/therapeutic use , Rats, Sprague-Dawley , Receptors, Angiotensin/antagonists & inhibitors , Vascular Endothelial Growth Factor AABSTRACT
Objective To investigate the clinical effect and safety of Epalrestat,an aldose reductase inhibitor(ARI),on patients with diabetic neuropathy.Methods 80 patients with diabetic neuropathy were randomly divided into two groups,one group were treated with Epalrestat,the other was treated with VitB12 for 16 weeks.All patients were measured on their symptoms,the physical signs and SNCV of medial nerve,ulnar nerve,peroneal nerve and tibial nerve during the treatment.Results The degrees of improvement were similar between the two groups.The subjective symptom and physical signs were significantly improved(P
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Object To investigate the chemical constituents of Buddlejae officinalis Maxim. , the relationship between their bioactivities, and the medicinal application of the herb. Methods Various chro-matographic techniques were employed for the isolation and purification of the constituents, including silica gel, Sephadex LH-20, and pre-HPLC. The structures of 11 isolated chemical compounds were elucidated by chemical and spectral analysis (NMR, IR, UV, and MS). The aldose reductase inhibiting test and test on DNA topoisomerase Ⅳ inhibitory effect were applied to evaluate the bioactivity of both the purified compounds and the crude fraction. Results Eleven compounds were isolated from the extracts of B. offic-inalis. They are four flavones and their glycosides; apigenin (Ⅰ), linarin (Ⅱ), apigenin-7-O-?-L-rhamnopyranosyl (1-6)-?-D-glucopyranoside (Ⅲ), and luteolin-7-O-?-D-glucoside (Ⅶ); four phenylen-thanoid glycosides: verbascoside (Ⅴ), isoacteoside (Ⅵ), cistanoside F, a and b (Ⅶ-1 and 2), campneo-side Ⅱ , a and b (Ⅷ-1 and 2); three triferpenoid saponins: mimengoside A (Ⅸ), mimengoside B (Ⅹ), songaroside A (Ⅺ). Some of the them (such as Ⅱ ,Ⅲ , and Ⅵ) showed the aldose reductase inhibitory activities with a higher inhibitory rate than that of quercetin (the positive control), others (such as Ⅰ,Ⅱ , Ⅴ, Ⅵ, and Ⅺ) displayed the inhibititory activities against the DNA topoisomerase Ⅳ . Conclusion Among all the isolated compounds, Ⅲ , Ⅶ-1 and 2, Ⅷ-1 and 2, and Ⅺ are separated for the first time both from the plant and the genus. Their bioactivities of bacteriostatic and against aldose reductase with DNA topoisomerase Ⅳ as target are tested for the first time and are related to the medicinal application of B. officinalis.
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The effect of ICI 128436, an aldose reductase inhibitor on the sorbitol metabolism in the mouse pancreatic islets during in vitro culture was observed. After culture for 72 hours, the levels of the sorbitol from the islets treated with the aldose reductase inhibitor were significantly decreased in comparison with those from the control islets. It denotes that the levels of sorbitolgenera-tion are closely related to the activity of aldose reductase, although the sorbitol may be synthctized in the pancreatic islets.
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Rat lens aldose reductase (AR) activity was assayed in this study with a fiuorometric method. Rat lenses were homogenized in Na, K-phosphate buffer and centrifuged at 19127 ? g, 4℃ for 15 min. The supernatant was reserved as enzyme fraction. The incubation mixture contained 135 mmol KHaPO4-Na2HPO4 buffer (pH 7.0), 100 mmol Li2SO4, 6 ?mol NADPH, 1.0 mmol DL-glyceraldehyde or 10 mmol glucose and 20/ul enzyme fraction. AR activity in diabetic rat lent have not been shown to be significantly higher than that of the con rols. This method can be used properly to screen AR inhibitors in vitro.