Background:Parkinson's disease(PD)is a progressive neurodegenerative disorder affecting a large number of elderly people worldwide.The current therapies for PD are symptom-based;they do not provide a cure but impr...Background:Parkinson's disease(PD)is a progressive neurodegenerative disorder affecting a large number of elderly people worldwide.The current therapies for PD are symptom-based;they do not provide a cure but improve the quality of life.Muscular dysfunction is the hallmark clinical feature of PD and oxidative stress and inflammation play a critical role in its pathogenesis.Epalrestat is used for the treatment of diabetic neuropathy and is known to improve antioxidative defense mechanisms in the CNS.Therefore,in this study,we investigated the role of Epalrestat in the reserpine induced mouse model of PD.Method:We used Swiss Albino mice for the PD model and tested for akinesia/bradykinesia,muscular rigidity,palpebral ptosis,and tremor,as well as conducting swim and open field tests.Brain samples were used to determine oxidative stress parameters and infiltration of immune cells.Results:Epalrestat treatment significantly improved akinesia and bradykinesia,muscular dysfunctions,tremor level,and gait functions compared to the reserpine group.It also improved the latency in the swim test.Eplarestat significantly reduced lipid peroxidation and NO concentration in different brain tissues and increased the activity of antioxidative enzymes,glutathione,catalase,and superoxide dismutase.Furthermore,Epalrestat reduced neuroinflammation by reducing the number of infiltrating immune cells.Conclusion:Eplarestat improves muscular dysfunction in PD by reducing oxidative stress and inflammation.展开更多
Recent Background: Diabetic neuropathy is one of the major complications in long standing hyperglycemic patients. Though exact mechanism of neuronal damage is unclear, accumulation of excess sorbitol through polyol pa...Recent Background: Diabetic neuropathy is one of the major complications in long standing hyperglycemic patients. Though exact mechanism of neuronal damage is unclear, accumulation of excess sorbitol through polyol pathway is believed to contribute significantly. Epalrestat and methylcobalamin are extensively used in this area to counter neuronal damage. This study was aimed to evaluate the combined effect of these drugs. Materials and Methods: A total of 220 patients with diabetic neuropathy were included in this study. The patients were divided into two groups;group A was administered combination of epalrestat 50 mg and methylcobalamin 500 mcg while group B was administered epalrestat 50 mg alone (both thrice daily). The treatment period was 12 weeks with monitoring on week 4, 8 and 12 of the study. At baseline and at follow up visits following parameters were evaluated: loss of sensation, burning sensation, numbness, muscle cramps, spontaneous pain, weakness, dizziness, loss of the thermal sensitivity, tendon reflexes, muscle strength and pain intensity using visual analog scale (VAS). Results: All the parameters were improved in both the groups compared to baseline. In group A significant improvement was seen on week 4 itself and continued for the rest of the study in all the measured parameters. Group B showed significant improvement from 8th week onwards. The inter-group difference is statistically significant in favour of the combination therapy. Conclusion: Combination of epalrestat and methylcobalamin is a better option for the treatment of diabetic neuropathy than epalrestat alone. Combination therapy was associated with faster onset and better symptomatic relief.展开更多
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-phas...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 different pH,temperatures,ionic strengths,oxidation and irradiation.The calibration curve was A=1.6×10^5C–1.3×10^3(r=0.999)with the liner range of 0.5–24μg/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.展开更多
An isocratic reversed-phase liquid chromatographic (LC) method is described for the determination of epalrestat and its three stereoisomers (degradation impurities) in drug substance. The LC separation system consiste...An isocratic reversed-phase liquid chromatographic (LC) method is described for the determination of epalrestat and its three stereoisomers (degradation impurities) in drug substance. The LC separation system consisted of a Hypersil C18 column (250 mm×4.6 mm, 5 μm) with a mobile phase comprising methanol, acetonitrile and water (volume ratio 60∶1∶50, pH 4.5) delivered at a flow rate of 1.6 mL/min and UV detection at 280 nm. The proposed LC method is simple and selective for the determination of the stereoisomers of epalrestat in the drug substance with a limit of detection and quantification of 3.9 μg/mL and 4.9 μg/mL, respectively. The stereoisomers were identified by liquid chromatography-mass spectrometry (LC-MS).展开更多
Objective:To investigate the effect of Epalrestat combined with Huoxue Huayu preparation on early diabetic retinopathy and its effect on serum oxidative stress and inflammatory factors.Methods:132 patients with early ...Objective:To investigate the effect of Epalrestat combined with Huoxue Huayu preparation on early diabetic retinopathy and its effect on serum oxidative stress and inflammatory factors.Methods:132 patients with early diabetic retinopathy from June 2017 to July 2019 in our hospital were randomly divided into the control group(66 cases)and the observation group(66 cases);The control group was treated with epalrestat,and the observation group was treated with epalrestat combined with ginkgo damo injection;The treatment effect,blood rheology indexes,serum oxidative stress indexes and inflammatory factor indexes of the two groups were compared.Results:The treatment efficiency of the observation group(96.96%)was significantly higher than that of the control group(84.84%)(P<0.05).After 3 months of treatment,the high-cut whole blood viscosity(3.62±0.45 mPa/s),low-cut whole blood viscosity(1.54±0.26 mPa/s),erythrocyte sedimentation rate(15.63±2.97 mm/s)of the observation group compared with the control group(4.57±0.52 mPa/s,2.91±0.30 mPa/s,22.36±3.38 mm/s)were significantly lower(P<0.05).After 3 months of treatment,the SOD(93.41±10.17 nmol/mL)and TAC(20.57±3.76 u/mL)of the observation group compared with the control group(82.26±9.45 nmol/mL,18.26±3.63 u/mL)were significantly higher(P<0.05),and the MDA of the observation group(9.22±1.98 u/mL)was significantly lower than that of the control group(12.13±1.06 u/mL)(P<0.05).After 3 months of treatment,the CRP(9.74±1.12 mg/L),IL-2(70.37±12.13 ng/L),TNF-a(11.36±2.08 ng/L)of the observation group compared with the control group(15.28±1.73 mg/L L,82.46±10.58 ng/L,16.28±2.43 ng/L)were significantly lower(P<0.05).Conclusion:Epalrestat combined with Huoxue Huayu preparation is more effective in the treatment of early diabetic retinopathy,and can significantly improve the blood rheology indexes,serum oxidative stress indexes and inflammatory factor indexes of patients.展开更多
Objective:To explore the influence of adjuvant epalrestat treatment of early diabetic nephropathy on renal function and oxidative stress.Methods:A total of 80 patients with early diabetic nephropathy who were treated ...Objective:To explore the influence of adjuvant epalrestat treatment of early diabetic nephropathy on renal function and oxidative stress.Methods:A total of 80 patients with early diabetic nephropathy who were treated in our hospital between January 2013 and February 2016 were collected and divided into observation group and control group according to single-blind parallel control. Control group of patients received routine therapy, and observation group of patients received adjuvant epalrestat treatment on this basis. After 8 weeks of treatment, automatic biochemical analyzer was used to detect the renal function indexes of two groups of patients;RIA method was used to detect the serum renal fibrosis index levels;enzyme-linked immunosorbent assay (ELISA) was used to detect serum oxidative stress index levels.Results:Before treatment, differences in serum renal function, renal fibrosis and oxidative stress index levels were not statistically significant between two groups of patients;after 8 weeks of treatment, serum renal function indexes Scr, BUN, CysC andβ2-MG levels of observation group were lower than those of control group, renal fibrosis indexes CⅣ, CTGF and TGF-β1 levels were lower than those of control group, oxidation indexes ROS, LHP and AOPPs levels were lower than those of control group, anti-oxidation indexes SOD, VitE, VitC and T-AOC levels were significantly higher than those of control group, and the differences were statistically significant.Conclusion:Adjuvant epalrestat therapy can optimize the renal function and reduce the systemic oxidative stress response in patients with early diabetic nephropathy.展开更多
Objective:To study the renal function, peroxidation damage and inflammatory injury after epalrestat combined with alprostadil treatment of early diabetic nephropathy.Methods:90 patients with early diabetic nephropathy...Objective:To study the renal function, peroxidation damage and inflammatory injury after epalrestat combined with alprostadil treatment of early diabetic nephropathy.Methods:90 patients with early diabetic nephropathy treated in our hospital between June 2011 and November 2015 were collected and divided into observation group and control group (n=45) according to the single-blind randomized control method. Observation group received epalrestat combined with alprostadil treatment, control group received alprostadil treatment alone, and the treatment of both groups lasted for 3 months. Before treatment and after 3 months of treatment, turbidimetric immunoassay was used to detect the renal function indexes in peripheral blood, rate method was used to detect the renal function indexes in urine, and ELISA method was used to detect the levels of peroxidation indexes and inflammation indexes.Results:Before treatment, differences in renal function, peroxidation damage and inflammatory damage indexes were not statistically significant between two groups of patients (P>0.05). After 3 months of treatment, creatinine (Scr), cystatin C (CysC),β2 microglobulin (β2-MG), N-acetyl-β-D-glucosaminidase (NAG), reactive oxygen species (ROS), advanced protein oxidation products (AOPPs), interleukin-8 (IL-8), interleukin-27 (IL-27) and procalcitonin (PCT) levels of observation group were lower than those of control group while catalase (CAT), total superoxide dismutase (TSOD), interleukin-4 (IL-4), interleukin-10 (IL-10) and interleukin-13 (IL-13) levels were higher than those of control group (P<0.05). Conclusions:Epalrestat combined with alprostadil can protect the renal function and inhibit the peroxidation damage and inflammatory injury in patients with early diabetic nephropathy.展开更多
基金We thank Ms Fahmida Zaman for her initial intellectual support for this projectWe are grateful to Ms Noshin Noorjahan for her editorial support for our manuscript.Department of Pharmaceutical Sciences at North South University provided the Laboratory space,including the equipment and basic reagents necessary to conduct this project.
文摘Background:Parkinson's disease(PD)is a progressive neurodegenerative disorder affecting a large number of elderly people worldwide.The current therapies for PD are symptom-based;they do not provide a cure but improve the quality of life.Muscular dysfunction is the hallmark clinical feature of PD and oxidative stress and inflammation play a critical role in its pathogenesis.Epalrestat is used for the treatment of diabetic neuropathy and is known to improve antioxidative defense mechanisms in the CNS.Therefore,in this study,we investigated the role of Epalrestat in the reserpine induced mouse model of PD.Method:We used Swiss Albino mice for the PD model and tested for akinesia/bradykinesia,muscular rigidity,palpebral ptosis,and tremor,as well as conducting swim and open field tests.Brain samples were used to determine oxidative stress parameters and infiltration of immune cells.Results:Epalrestat treatment significantly improved akinesia and bradykinesia,muscular dysfunctions,tremor level,and gait functions compared to the reserpine group.It also improved the latency in the swim test.Eplarestat significantly reduced lipid peroxidation and NO concentration in different brain tissues and increased the activity of antioxidative enzymes,glutathione,catalase,and superoxide dismutase.Furthermore,Epalrestat reduced neuroinflammation by reducing the number of infiltrating immune cells.Conclusion:Eplarestat improves muscular dysfunction in PD by reducing oxidative stress and inflammation.
文摘Recent Background: Diabetic neuropathy is one of the major complications in long standing hyperglycemic patients. Though exact mechanism of neuronal damage is unclear, accumulation of excess sorbitol through polyol pathway is believed to contribute significantly. Epalrestat and methylcobalamin are extensively used in this area to counter neuronal damage. This study was aimed to evaluate the combined effect of these drugs. Materials and Methods: A total of 220 patients with diabetic neuropathy were included in this study. The patients were divided into two groups;group A was administered combination of epalrestat 50 mg and methylcobalamin 500 mcg while group B was administered epalrestat 50 mg alone (both thrice daily). The treatment period was 12 weeks with monitoring on week 4, 8 and 12 of the study. At baseline and at follow up visits following parameters were evaluated: loss of sensation, burning sensation, numbness, muscle cramps, spontaneous pain, weakness, dizziness, loss of the thermal sensitivity, tendon reflexes, muscle strength and pain intensity using visual analog scale (VAS). Results: All the parameters were improved in both the groups compared to baseline. In group A significant improvement was seen on week 4 itself and continued for the rest of the study in all the measured parameters. Group B showed significant improvement from 8th week onwards. The inter-group difference is statistically significant in favour of the combination therapy. Conclusion: Combination of epalrestat and methylcobalamin is a better option for the treatment of diabetic neuropathy than epalrestat alone. Combination therapy was associated with faster onset and better symptomatic relief.
文摘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 different pH,temperatures,ionic strengths,oxidation and irradiation.The calibration curve was A=1.6×10^5C–1.3×10^3(r=0.999)with the liner range of 0.5–24μg/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.
文摘An isocratic reversed-phase liquid chromatographic (LC) method is described for the determination of epalrestat and its three stereoisomers (degradation impurities) in drug substance. The LC separation system consisted of a Hypersil C18 column (250 mm×4.6 mm, 5 μm) with a mobile phase comprising methanol, acetonitrile and water (volume ratio 60∶1∶50, pH 4.5) delivered at a flow rate of 1.6 mL/min and UV detection at 280 nm. The proposed LC method is simple and selective for the determination of the stereoisomers of epalrestat in the drug substance with a limit of detection and quantification of 3.9 μg/mL and 4.9 μg/mL, respectively. The stereoisomers were identified by liquid chromatography-mass spectrometry (LC-MS).
基金2019 Hainan Province Medical and Health Research Project(No.1901320244S2007)。
文摘Objective:To investigate the effect of Epalrestat combined with Huoxue Huayu preparation on early diabetic retinopathy and its effect on serum oxidative stress and inflammatory factors.Methods:132 patients with early diabetic retinopathy from June 2017 to July 2019 in our hospital were randomly divided into the control group(66 cases)and the observation group(66 cases);The control group was treated with epalrestat,and the observation group was treated with epalrestat combined with ginkgo damo injection;The treatment effect,blood rheology indexes,serum oxidative stress indexes and inflammatory factor indexes of the two groups were compared.Results:The treatment efficiency of the observation group(96.96%)was significantly higher than that of the control group(84.84%)(P<0.05).After 3 months of treatment,the high-cut whole blood viscosity(3.62±0.45 mPa/s),low-cut whole blood viscosity(1.54±0.26 mPa/s),erythrocyte sedimentation rate(15.63±2.97 mm/s)of the observation group compared with the control group(4.57±0.52 mPa/s,2.91±0.30 mPa/s,22.36±3.38 mm/s)were significantly lower(P<0.05).After 3 months of treatment,the SOD(93.41±10.17 nmol/mL)and TAC(20.57±3.76 u/mL)of the observation group compared with the control group(82.26±9.45 nmol/mL,18.26±3.63 u/mL)were significantly higher(P<0.05),and the MDA of the observation group(9.22±1.98 u/mL)was significantly lower than that of the control group(12.13±1.06 u/mL)(P<0.05).After 3 months of treatment,the CRP(9.74±1.12 mg/L),IL-2(70.37±12.13 ng/L),TNF-a(11.36±2.08 ng/L)of the observation group compared with the control group(15.28±1.73 mg/L L,82.46±10.58 ng/L,16.28±2.43 ng/L)were significantly lower(P<0.05).Conclusion:Epalrestat combined with Huoxue Huayu preparation is more effective in the treatment of early diabetic retinopathy,and can significantly improve the blood rheology indexes,serum oxidative stress indexes and inflammatory factor indexes of patients.
文摘Objective:To explore the influence of adjuvant epalrestat treatment of early diabetic nephropathy on renal function and oxidative stress.Methods:A total of 80 patients with early diabetic nephropathy who were treated in our hospital between January 2013 and February 2016 were collected and divided into observation group and control group according to single-blind parallel control. Control group of patients received routine therapy, and observation group of patients received adjuvant epalrestat treatment on this basis. After 8 weeks of treatment, automatic biochemical analyzer was used to detect the renal function indexes of two groups of patients;RIA method was used to detect the serum renal fibrosis index levels;enzyme-linked immunosorbent assay (ELISA) was used to detect serum oxidative stress index levels.Results:Before treatment, differences in serum renal function, renal fibrosis and oxidative stress index levels were not statistically significant between two groups of patients;after 8 weeks of treatment, serum renal function indexes Scr, BUN, CysC andβ2-MG levels of observation group were lower than those of control group, renal fibrosis indexes CⅣ, CTGF and TGF-β1 levels were lower than those of control group, oxidation indexes ROS, LHP and AOPPs levels were lower than those of control group, anti-oxidation indexes SOD, VitE, VitC and T-AOC levels were significantly higher than those of control group, and the differences were statistically significant.Conclusion:Adjuvant epalrestat therapy can optimize the renal function and reduce the systemic oxidative stress response in patients with early diabetic nephropathy.
文摘Objective:To study the renal function, peroxidation damage and inflammatory injury after epalrestat combined with alprostadil treatment of early diabetic nephropathy.Methods:90 patients with early diabetic nephropathy treated in our hospital between June 2011 and November 2015 were collected and divided into observation group and control group (n=45) according to the single-blind randomized control method. Observation group received epalrestat combined with alprostadil treatment, control group received alprostadil treatment alone, and the treatment of both groups lasted for 3 months. Before treatment and after 3 months of treatment, turbidimetric immunoassay was used to detect the renal function indexes in peripheral blood, rate method was used to detect the renal function indexes in urine, and ELISA method was used to detect the levels of peroxidation indexes and inflammation indexes.Results:Before treatment, differences in renal function, peroxidation damage and inflammatory damage indexes were not statistically significant between two groups of patients (P>0.05). After 3 months of treatment, creatinine (Scr), cystatin C (CysC),β2 microglobulin (β2-MG), N-acetyl-β-D-glucosaminidase (NAG), reactive oxygen species (ROS), advanced protein oxidation products (AOPPs), interleukin-8 (IL-8), interleukin-27 (IL-27) and procalcitonin (PCT) levels of observation group were lower than those of control group while catalase (CAT), total superoxide dismutase (TSOD), interleukin-4 (IL-4), interleukin-10 (IL-10) and interleukin-13 (IL-13) levels were higher than those of control group (P<0.05). Conclusions:Epalrestat combined with alprostadil can protect the renal function and inhibit the peroxidation damage and inflammatory injury in patients with early diabetic nephropathy.
