AKR1B10 inhibitor enhances the inhibitory effect of sorafenib on liver cancer xenograft / 中华肝脏病杂志

Objective@#To investigate the inhibitory effect of AKR1B10 inhibitor combined with sorafenib on hepatocellular carcinoma (HCC) xenograft growth.@*Methods@#HepG2 xenograft model was established in nude mice. The mice were then randomly divided into four groups: control group, epalrestat monotherapy group, sorafenib monotherapy group and combination treatment group. Tumor volume, tumor weight, T/C ratio and the change in body weight of nude mice in each group were compared to evaluate the curative effect. Immunohistochemistry staining was used to detect the expression of Ki-67 in tumor tissues to evaluate the proliferation status of tumor cells. One-way analysis of variance was used to compare the differences between the groups. Student’s t-test was used to test means of two groups and chi-square test was used for multiple samples.@*Results@#The differences of the grafted tumor volume before and after treatment between the control group, epalrestat group, sorafenib group and combined therapy group was 238.940 ± 39.813, 124.991 ± 84.670, -26.111 ± 11.518, and -54.072 ± 17.673(mm3), respectively, (F = 37.048, P < 0.001). The tumor mass were 0.273 ± 0.140, 0.158 ± 0.078, 0.079 ± 0.054, 0.045 ± 0.024 (g), (F = 16.594, P < 0.001); T/C ratio were 100%, 57.9%, 28.9%, 16.5%, and Ki-67 positive rate were 23.295 ± 6.218, 13.503 ± 3.392, 7.325 ± 2.257, 4.664 ± 1.189 (%), (χ2 = 822.203, P < 0.001) . The tumor volume (t = -3.579, P = 0.002) and Ki-67 positive rate (t = -10.003, P < 0.001) in epalrestat monotherapy group were significantly lower than control group. The tumor volume (t = 2.056, P = 0.025), tumor mass (t = 2.101, P = 0.043), and Ki-67 positive rate (t = -2.850, P = 0.005) in combination treatment group were significantly lower than sorafenib monotherapy group. Compared with the control group, the body weight of nude mice in the treatment group decreased to a certain extent, but there was no statistically significant difference between epalrestat monotherapy group and control group (t = -1.599, P = 0.262), and combined therapy and sorafenib monotherapy group (t = -0.051, P = 0.96).@*Conclusion@#AKR1B10 inhibitor enhanced the inhibitory effect of sorafenib on hepatocellular carcinoma xenograft.

Study on degradation kinetics of epalrestat in aqueous solutions and characterization of its major degradation products under stress degradation conditions by UHPLC-PDA-MS/MS / 药物分析学报

Drug stability is closely related to drug safety and needs to be considered in the process of drug production, package and storage. To investigate the stability of epalrestat, a carboxylic acid derivative, a reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed in this study and applied to analyzing the degradation kinetics of epalrestat in aqueous solutions in various conditions, such as dif-ferent pH, temperatures, ionic strengths, oxidation and irradiation. The calibration curve was A=1.6 × 105C–1.3 × 103 (r=0.999) with the liner range of 0.5–24 μg/mL, the intra-day and inter-day precision was less than 2.0%, as was the repeatibility. The average accuracy for different concentrations was more than 98.5%, indicating that perfect recoveries were achieved. Degradation kinetic parameters such as degradation rate constants (k), activation energy (Ea) and shelf life (t0.9) under different conditions were calculated and discussed. The results indicated that the degradation behavior of epalrestat was pH-dependent and the stability of epalrestat decreased with the rised irradiation and ionic strength;however, it was more stable in neutral and alkaline conditions as well as lower temperatures. The results showed that the degradation kinetics of epalrestat followed first-order reaction kinetics. Furthermore, the degradation products of epalrestat under stress conditions were identified by UHPLC-PDA-MS/MS, with seven degradation products being detected and four of them being tentatively identified.

Clinical observation on the curative effect of epalrestat combined with compound anisodine in treatment of non-proliferative diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To investigate the clinical value of epalrestat combined with compound anisodine in treatment of non-proliferative diabetic retinopathy(NPDR).<p>METHODS: According to the random remainder method, they were divided into A, B and C three groups. Group A was treated with calcium dobesilate, group B was treated with epalrestat, and group C was treated with epalrestat combined with compound anisodine. All groups were treated for 6mo. The BCVA and fundus color photos, fundus fluorescein angiography(FFA), oscillatory potentials of electroretinogram(ERG-Ops)and optical coherence tomography(OCT)were performed before and after 1mo, 3mo and 6mo of treatment. The therapeutic effect was evaluated. <p>RESULTS: Before treatment, there was no statistical difference among the three groups in BCVA, Ops wave amplitude or central macular thickness(<i>P</i>>0.05). The BCVA was improved, Ops wave amplitude was increased and the central macular thickness was decreased in the three groups after 1mo, 3mo and 6mo of treatment. Compared with the same group before treatment, there were statistically significant differences(<i>P</i><0.05). The improvement of visual acuity at different time and the increase of Ops wave amplitude were better in group B than group A, better in group C than group B, while the decrease of central macular thickness was greater in group B than group A, greater in group C than group B(all <i>P</i><0.05). The total effective rate among the three groups were significant difference(<i>P</i><0.05), and the total effective rate of group C was better than that of group B and group A(<i>P</i><0.0167).<p>CONCLUSION: Epalrestat combined with compound anisodine is effective in treatment of DR. The combined treatment can significantly improve the visual acuity, relieve macular edema and promote the recovery of retinal function.

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.

Clinical Observation of Compound Xiongshao Capsules in the Treatment of Diabetic Peripheral Neuropathy / 中国药房

OBJECTIVE:To observe clinical efficacy and safety of Compound xiongshao capsules in the treatment of diabetic peripheral neuropathy (DPN).METHODS:A total of 97 DPN patients selected from our hospital during Jun.2015-Apr.2016 were divided into group A (compound xiongshao treatment group,46 cases) and control group (51 cases) according to random number table.The latter was divided into group B (epalrestat+beraprost sodium group,12 cases),group C (fursultiamine+mecobalamin group,12 cases) and group D (epalrestat group,27 cases) according to clinical symptoms and economic situation of patients.Four groups were given antidiabetic drugs for blood glucose control.Based on it,group A was additionally given Compound xiongshao capsules 0.9 g,tid;group B was additionally given Epalrestat tablets 50 mg,tid+Beraprost sodium tablets 40 μg,tid;group C was additionally given Fursultiamine tablets 50 mg,tid+Mecobalamin tablets 0.5 mg,rid;group D was additionally given Epalrestat tablets 50 mg,tid.All groups were treated for 6 months.Clinical efficacies were observed.TCSS scores,motor nerve conduction velocity (MCV),sensory nerve conduction velocity (SCV),incubation period and amplitude of median nerve and common peroneal nerve,the levels of hemorheology indexes,blood glucose,glycosylated hemoglobin,blood lipid,serum creatinine were compared before and after treatment.The occurrence of ADR was recorded.RESULTS:Total response rates of group A and B (82.61％,83.33％)were significantly higher than those of group C and D (33.33％,66.67％),total response rate of group D was significantly higher than that of group C,with statistical significance (P＜0.05).Before treatment,there was no statistical significance in TCSS scores,MCV,SCV,incubation period and amplitude of median nerve,MCV and amplitude of common peroneal never,SCV,incubation period and amplitude of common peroneal never or whole blood high-shear viscosity among 4 groups (P＞0.05).After treatment,TCSS scores of group A,B and D were decreased significantly compared to before treatment,and those of group A and B were lower than those of group C and D,with statistical significance (P＜0.05).MCV,incubation period and amplitude of median nerve in group A and B,amplitude of median nerve in group C,MCV and amplitude of median nerve in group D were significantly better than before treatment;MCV,incubation period and amplitude of median nerve in group A and B were significantly better than group C and D,with statistical significance (P＜0.05).MCV,incubation period and amplitude of common peroneal never in group A,B,C were significantly better than before treatment,MCV and amplitude of common peroneal never in group A,B were significantly better than group C,D;the improvement of incubation period of common peroneal never in group A,B,D were significantly better than group C,with statistical significance (P＜0.05).SCV,incubation period and amplitude of median nerve,SCV and amplitude of common peroneal nerve in group A,B and D were significantly better than before treatment;SCV,incubation period and amplitude of median nerve,SCV and amplitude of common peroneal nerve in group A,SCV,incubation period and amplitude of median nerve and amplitude of common peroneal nerve in group B were significantly better than group C and D;SCV of median nerve in group D was significantly better than group C,with statistical significance (P＜0.05).Whole blood high-shear viscosity of group A was decreased significantly compared to before treatment,and significantly lower than those of group B,C and D,with statistical significance (P＜0.05).There was no statistical significance in total response rate and TCSS score between group A and B,and in the levels of blood glucose,glycosylated hemoglobin,blood lipid or serum creatinine among 4 groups (P＞0.05).No obvious ADR was found in 4 groups.CONCLUSIONS:Compound xiongshao capsules shows significant therapeutic efficacy for DPN,and improves nerve conduction velocity,incubation period and amplitude of median nerve and common peroneal nerve,whole blood high-shear viscosity.Its effect is similar to that of epalrestat combined with beraprost sodium,and better than those of fursultiamine combined with mecobalamin,epalrestat alone.It does not affect the blood glucose,blood lipid and serum creatinine levels with good safety.

Clinical study of alprostadil combined with epalrestat and methylcobalamin in the treatment of type 2 diabetic peripheral neuropathy / 中国基层医药

Objective To study the effect of alprostadil combined with epalrestat and methylcobalamin in the treatment of type 2 diabetic peripheral neuropathy.Methods From January 2014 to June 2016,120 patients with type 2 diabetic peripheral neuropathy in the First People's Hospital of Baiyin were randomly divided into two groups according to the random number table method.64 patients of the observation group were given the treatment of alprostadil,epalrestat combined with methylcobalamin.56 patients of the control group were given the treatment of alprostadil and methylcobalamin.And the two groups were treated for 4 weeks.The blood glucose,clinical symptoms,adverse reaction,nerve conduction velocity index were compared between the two groups before and after treatment.Results The fasting blood glucose and 2-hour postprandial blood glucose of the two groups after treatment were significantly decreased (t =18.20,17.61,15.75,23.69,all P ＜ 0.05),and the conduction velocity of the common peroneal nerve,the median nerve and the ulnar nerve in the observation group were significantly higher than those in the control group (t =1.989,2.638,3.026,2.187,2.619,1.997,all P ＜ 0.05).The total effective rate of the observation group was significantly higher than that of the control group(95.3％ vs.82.1％,x2 =4.54,P ＜0.05).There were no statistically significant differences in the blood glucose and the incidence rate of adverse reactions between the two groups (t =0.267,0.176,0.695,0.658,x2 =1.356,all P ＞ 0.05).Conclusion Alprostadil combined with epalrestat and methylcobalamin in the treatment of type 2 diabetic peripheral neuropathy has good effect.

Effect of epalrestat on diabetic peripheral neuropathy: a randomized placebo -controlled trails Meta-analysis / 中国基层医药

Objective To assess the effect and safety of epalrestat on diabetic peripheral neuropathy ( DPN) . Methods Retrieved from PubMed,Cochrane Library,CNKI,VIP,CBM and Wanfang database ,RCTs about epalrestat in the treatment of DPN were included from establishment to July 2017 and comprehensively evaluated .Two reviewers independently screened literature according to the inclusion and exclusion criteria , extracted data , assessed the risk bias of included studies , and then analysis was performed using the RevMan 5.3 software.Results A total of 14 RCTs involved 1945 patients were included .The results of systematic review and Meta -analysis showed that epalrestat could significantly improve DPN compared with the placebo /blank control group ( OR =8.01,95％CI:4.48-14.32,P<0.01;OR=2.49,95％CI:1.71-3.65,P<0.01).Compared with the placebo group and the blank control group,epalrestat could significantly improve the median sensory nerve conduction velocity ( OR=3.92,95％Cl:1.37-6.47,P<0.01),peroneal nerve conduction velocity (OR=4.87,95％CI:2.35-7.39,P<0.01) and ulnar nerve conduction velocity ( OR =4.58, 95％CI:2.54-6.63, P <0.01 ).The major adverse reactions were gastrointestinal reactions ,nausea and vomiting ,but no serious adverse reactions were observed in the epalrestat group , compared with the placebo/blank control group,the difference was statistically significant (OR =12.87,95％CI:2.35-70.50,P<0.01).Conclusion Epalrestat can effectively treat DPN through improving the body's sensory nerve conduction velocity,and it has no serious adverse reactions .Since the limitation of quality and quantity of included studies,large-scale and high-quality randomized double -blinding controlled trails are needed to verify the above conclusion.

Clinical efficacy and safety of a new epalrestat in diabetic peripheral neuropathy—a multicenter and randomized controlled clinical trial / 中华内分泌外科杂志

Objective To evaluate the efficacy and safety of new epalrestat on diabetic peripheral neuropathy (DPN) compared with Tang Lin.Methods A total of 235 patients with DPN were enrolled in our study.They were randomly divided into two groups:the new epalrestat group (n=117) and the Tang Lin group (n=118).Their clinical,biochemistry,electrocardiogram,clinical symptoms and physical examinations,by using Michigan Neuropathy Screening Instrument (MNSI),and electrophysiological assessments were performed.Results The mean changes of MNSI scores both decreased compared with baseline in two groups after treatment for 12 weeks (P＜0.05) and nerve conduction velocity improved in the two groups (P＜0.05),but there were no difference of MNSI scores and nerve conduction velocity between the two groups.There was no difference of adverse event,blood pressure,heart rate,blood and urine routine examinations,liver and renal function between the two groups.Conclusion The new epalrestat is effective and safe as Tang Lin in treatment of DPN.

Clinical Observation of Epalrestat Combined with Lipoic Acid in the Treatment of Diabetic Peripheral Neu-ropathy / 中国药房

OBJECTIVE:To observe the effects of epalrestat combined with lipoic acid on nerve function,oxidative stress and inflammatory reaction in patients with diabetic peripheral neuropathy(DPN). METHODS:From Jan. 2013 to Jan. 2016,150 pa-tients were selected from our hospital and then divided into group A,B,C according to random number table,with 50 cases in each group. Group A was given Lipoic acid injection 600 mg,ivgtt,qd;group B was given Epalrestat tablet 50 mg,po,tid;group C was given lipoic acid+epalrestat,same usage and dosage as above. TSS score,MNCV,SNCV,oxidative stress indexes (SOD and MDA)and inflammatory indexes(TNF-α and IL-6),as well as blood pressure,blood lipid and blood glucose indexes were compared among 3 groups before and after treatment. The occurrence of ADR were observed. RESULTS:Before treatment, there was no statistical significance in above indexes among 3 groups (P>0.05). Compared to before treatment,TSS score, MDA,TNF-α and IL-6 levels of 3 groups were decreased significantly after treatment;MNCV and SNCV were speeded up signifi-cantly,and SOD level was increased significantly;each index of group C was better than that of group A and B,with statistical significance(P0.05). SBP and FPG after treatment of 3 groups were decreased significantly than before treatment,while HDL-C was increased significantly,with statistical signifi-cance(P0.05). No obvious ADR was found in 3 groups. CON-CLUSIONS:Epalrestat combined with lipoic acid can effectively improve nerve function in DPN patients by inhibiting oxidant stress and inflammatory reaction with good safety. The effect of drug combination is better than single drug.

Effects of epalrestat combined with methylcobalamin on quality of life of patients with diabetic peripheral neuropathy / 中国基层医药

Objective To evaluate the effect of epalrestat combined with methylcobalamin on quality of life of patients with diabetic peripheral neuropathy.Methods 124 patients with diabetic peripheral neuropathy were randomly divided into the control group and the observation group according to the random number table, each group had 62 cases.The two groups were treated on the basis of the effective control of blood glucose and medication to control peripheral neuropathy, the control group used mecobalamin, the observation group used epalrestat combined with methylcobalamin, the two groups were treated continuously for 60 days.The effects of two main physiological changes, clinical efficacy and quality of life were observed.Results The total effective rate of the observation group was 95.2%,which was higher than 80.6% of the control group, the difference was statistically significant(x2=3.072,P<0.05).The fasting plasma glucose(FPG),postprandial 2 h plasma glucose(2 h PPG), glycosylated hemoglobin(HbA1c) were improved compared with before treatment, the differences were statistically significant(all P<0.05),which of the observation group improved significantly better than the control group, the differences were statistically significant(all P<0.05).The evaluation indicators of body pain(BP),social function(SF), role physiological(RP) and mental health(MH) had statistically significant differences compared with the control group (t=16.964,44.583,30.204,44.114,all P<0.05).Conclusion Using epalrestat combined with methylcobalamin tablets in the treatment of patients with diabetic peripheral neuropathy can significantly improve blood glucose levels, clinical symptoms, the quality of life of patients and it has great clinical significance.

Preparation of Epalrestat Solid Dispersion by Hot-Melt Extrusion Technique / 中国药学杂志

OBJECTIVE: To prepare epalrestat (EP) solid dispersion by holt-melt extrusion (HME) technique in order to enhance its dissolution rate. METHODS: Optimal formula was obtained by screening the carrier type and drug proportion. The dispersion state of EP in the solid dispersion and physical mixture were studied with differential X-ray diffraction (X-RD), Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC) analysis techniques. RESULTS: Poloxamer 188 was selected as the carrier with the optimal ratio of Poloxamer188 to EP of 1∶3. The final solid powder product was homogeneous dispersion in light yellow color without any agglomerate. CONCLUSION: The carrier of EP solid dispersion has significant impact on the dissolution behavior and state of EP. Using Poloxamer 188 as the carrier, holt-melt extrusion is an effective technology for improving the in vitro dissolution of EP.

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.

Clinical Efficacy of α-Lipoic Acid versus Epalrestat in the Treatment of Diabetic Peripheral Neuropathy:A Systematic Review / 中国药房

OBJECTIVE:To systematically review the efficacy of α-lipoic acid versus epalrestat in the treatment of diabetic pe-ripheral neuropathy(DPN),and provide evidence-based reference for clinic. METHODS:Retrieved from CJFD,CBM,VIP,Wan-fang Database and PubMed,randomized controlled trials(RCT)about α-lipoic acid versus epalrestat in the treatment of DPN were collected,and the study was screened by inclusion and exclusion criteria. Meta-analysis was performed by using Rev Man 5.3 soft-ware after data extraction and quality evaluation by Cochrane software. RESULTS:Totally 6 RCTs were enrolled,involving 408 pa-tients. Results of Meta-analysis showed,compared with epalrestat,there were no significant differences in the total effective rate [RR=0.98,95%Cl(0.84,1.15),P=0.81],motor nerve conduction velocity [median nerve:MD=1.02,95%Cl(-1.10,3.14),P=0.34;common peroneal nerve:MD=0.23,95%Cl(-1.11,1.58),P=0.73] and sensory nerve conduction velocity [median nerve:MD=1.10,95%Cl(-0.39,2.59),P=0.15;common peroneal nerve:MD=0.95,95%Cl(-1.47,3.36),P=0.44] in α-lipoic acid group. CONCLUSIONS:The efficacy of α-lipoic acid is similar to epalrestat in the treatment of DPN,as well as the motor nerve conduction velocity and sensory nerve conduction velocity of median nerve or common peroneal nerve.

Clinical effect of epalrestat combined with methylcobalamin in the treatment of diabetic peripheral neuropathy / 中国基层医药

Objective To explore the clinical effect of epalrestat combined with methylcobalamin in the treatment of diabetic peripheral neuropathy.Methods 88 patients with diabetic peripheral neuropathy were chosen from September 2014 to September 2016 in our hospital.The patients were randomly divided into two groups,The control group was treated with conventional treatment,the observation group was given epalrestat combined with methylcobalamin based on the conventional treatment.The effect of the two groups was compared.Results The total effective rate of the observation group was 95.5 ％ (42/44),which was significantly higher than 70.5 ％ (31/44) of the control group,the difference was statistically significant(x2 =9.029,P =0.007).Before treatment,the median nerve and common peroneal nerve sensory conduction velocity betweem two groups had no significant differences (t =0.293,0.920,P =0.704,0.096).After treatment,the median nerve conduction velocity and peroneal nerve total sensory conduction velocity in the observation group were (46.2 ± 4) m/s,(42.4 ± 6.3) m/s,which were significantly higher than those in the control group(t =9.038,7.039,P =0.001,0.004).Conclusion Epalrestat combined with methylcobalamin in the treatment of patients with diabetic peripheral neuropathy can effectively improve the nerve conduction velocity.

Epalrestat,alprostadil combined with lipoic acid in the treatment of 44 elderly patients with diabetic peripheral neuropathy / 中国基层医药

Objective To investigate the effect of epalrestat,alprostadil combined with lipoic acid in the treatment of 44 elderly patients with diabetic peripheral neuropathy.Methods 44 elderly patients with diabetic peripheral neuropathy were selected,according to the random number table method they were divided into control group and observation group,22 cases in each group.The control group was treated with mecobalamin,the observation group was treated with epalrestat,alprostadil combined with lipoic acid.The clinical effects were compared between the two groups.Results The total effective rate of the observation group was 95.4%,which of the control group was 72.7%,the difference between the two groups was statistically significant(χ2 =7.94,P <0.05).In the observation group,the peroneal nerve and median nerve changes after treatment were significantly better than the control group,the differences were statistically significant(all P <0.05).Conclusion Epalrestat,alprostadil combined with lipoic acid in the treatment of elderly diabetic patients with peripheral neuropathy has obviously curative effect, and it can effectively improve the nerve conduction function.It is worthy of wide application in clinical treatment.

Clinical efficacy and safety of epalrestat in diabetic neuropathy-A multicenter randomized controlled clinical trial / 中华内分泌代谢杂志

Objective To evaluate the efficacy and safety of epalrestat, an aldose reductase inhibitor, and epalrestat plus methylcobalamine on diabetic peripheral neuropathy, as compared with methylcobalamine. Methods A total of 444 subjects with diabetic neuropathy were enrolled in the study, and divided into methylcobalamine group ( n= 145 ) , epalrestat group ( n = 143 ) , and methylcobalamine combined with epalrestat group ( n = 156 ) . Therapeutic efficacay was assessed in terms of clinical symptoms and physical examinations by using Michigan Neuropathy Screening Instrument ( MNSI ) , and electrophysiological assessments. Results After 4 to 12-weeks′treatment, symptoms and signs of neuropathy ( using MNSI ) are significantly improved in the three groups ( P0. 05). Conclusion Epalrestat is effective and safe in the treatment of diabetic neuropathy. Furthermore, epalrestat is more efficacious in ameliorating symptoms and MNCV of neuropathy than methylcobalamine. However, while no improved efficacy is shown with the combined treatment.

Amelioration of Bleomycin-induced Pulmonary Fibrosis of Rats by an Aldose Reductase Inhibitor, Epalrestat

Aldose reductase (AR) is known to play a crucial role in the mediation of diabetic and cardiovascular complications. Recently, several studies have demonstrated that allergen-induced airway remodeling and ovalbumin-induced asthma is mediated by AR. Epalrestat is an aldose reductase inhibitor that is currently available for the treatment of diabetic neuropathy. Whether AR is involved in pathogenesis of pulmonary fibrosis and whether epalrestat attenuates pulmonary fibrosis remains unknown. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/kg) in rats. Primary pulmonary fibroblasts were cultured to investigate the proliferation by BrdU incorporation method and flow cytometry. The expression of AR, TGF-beta1, alpha-SMA and collagen I was analyzed by immunohistochemisty, real-time PCR or western blot. In vivo, epalrestat treatment significantly ameliorated the bleomycin-mediated histological fibrosis alterations and blocked collagen deposition concomitantly with reversing bleomycin-induced expression up-regulation of TGF-beta1, AR, alpha-SMA and collagen I (both mRNA and protein). In vitro, epalrestat remarkably attenuated proliferation of pulmonary fibroblasts and expression of alpha-SMA and collagen I induced by TGF-beta1, and this inhibitory effect of epalrestat was accompanied by inhibiting AR expression. Knockdown of AR gene expression reversed TGF-beta1-induced proliferation of fibroblasts, up-regulation of alpha-SMA and collagen I expression. These findings suggest that AR plays an important role in bleomycin-induced pulmonary fibrosis, and epalrestat inhibited the progression of bleomycin-induced pulmonary fibrosis is mediated via inhibiting of AR expression.

Effect of Epalrestat on Heart Rate Variability in Patients with Diabetic Asymptomatic Myocardial Ischemia / 中国药师

Objective:To observe the effect of epalrestat on the heart rate variability in diabetes patients with silent myocardial is-chemia. Methods:Totally 60 patients were randomly divided into the control group and the treatment group with 30 cases in each. The two groups were given insulin or other routine drugs to keep blood sugar under control, ARB or ACEI and CCB to bring high blood pres-sure down, and statins to regulate lipid and anti-platelet aggregation, and both groups were without the use of beta blockers. The treat-ment group was given epalrestat 50mg three times a day for 4 weeks additionally. The indices of FPG, 2hPG, HbA1c, SBP, DBP, T-CHOL, TG, HDL-C, LDL-C and heart rate variability were observed after the treatment. Results: Compared with those before the treatment, the values of FPG, 2HPG, HbA1C, SBP, DBP, T-CHOL and LDL-c were decreased after the treatment in the two groups, and the differences were statistically significant (P 0. 05). After the treatment, SDNN, SDANN, SDNNI, RMSSD, PNN50 and Mean HR in the treatment group were obviously im-proved, which were better than those in the control group (P<0.05). The adverse reactions in the two groups were similar (P<0. 05). Conclusion:Epalrestat can significantly improve HRV-related indicators in the diabetes patients with silent myocardial ischemi-a, which can reduce the risk of sudden death without significant adverse reactions in the combination with other drugs.

Clinical efficacy of Shuxuening injection combined with epalrestat for diabetic nephropathy / 中国生化药物杂志

Objective To explore the clinical efficacy of Shuxuening combined with epalrestat in the treatment of diabetic nephropathy. Methods Eighty patients from March 2014 to June 2015 in Metabolic Disease Department of the Second Hospital of Tianjin were randomly divided into observation group and control group with 40 patients in each group.The control group received epalrestat, and the observation group received Shuxuening injection on the baisis of control group. The related indicators were compared between two groups.Results After treatment, the 24 h-urine microalbumin, plasma low density lipoprotein and serum creatinine in observation group [(239.31 ±106.54)mg/L,(2.45 ±0.55)mmol/L,(95.54 ± 22.13)mol/L]were lower than those in control group [(349.90 ±148.40),(3.41 ±0.52),(108.76 ±34.30)](P<0.05).The β2-microglobulin (β2-MG) and plasma high-sensitive C-reactive protein (hs-CRP) in observation group [(0.39 ±0.06),(6.31 ±1.58)mg/L]were lower than those in control group [(0.49 ±0.12),(7.89 ±1.35)](P<0.05).The total efficacy in observation group was higher than that in control group (70.0%vs.45.0%,P<0.05).Conclusion Shuxuening injection joint epalrestat has the exact efficacy in treatment of patients with diabetic nephropathy.

The contrast of epalrestat and mecobalamine in improving diabetic peripheral neuropathy / 中国医师杂志

Objective To compare the curative effect of Epalrestat and mecobalamine .Methods Epalrestat to treat 48 pa-tionts in DPN and mecobalamine to treat 42,measuring blood sugar ,blood pressure, blood fat and body mass index (BMI) prior and post treatment ,and measuring the MCV and SCV of nervus medianus ,nervus peronaeus connunis and nervus tibialis with EMG .Re-sults The symptom of the two sets have all been improved after the treatment ,and the effective power of Epalrestat and mecobalamine is 92.7% and 80.5% respectively.mean while there is improvement in MCV and SCV of nervus medianus ,nervus peronaeus connunis and nervus tibialis,and is more obvious in the set of Epalrestat ( P <0.01).In the whole process of the treat of the two sets ,no one appear to have adverse reactions .Conclusions Epalrestat has significant curative effect with less adverse reactions , and deserves to be spreaded in clinic.