Objectives:According to the findings of randomized controlled trials,blood lipid levels in patients with coronary heart disease(CHD)can be significantly decreased through a combination of pitavastatin and ezetimibe;ho...Objectives:According to the findings of randomized controlled trials,blood lipid levels in patients with coronary heart disease(CHD)can be significantly decreased through a combination of pitavastatin and ezetimibe;however,the effects and clinical applications of this treatment remain controversial.This meta-analysis was aimed at objectively assessing the efficacy and safety of pitavastatin and ezetimibe in lowering blood lipid levels.Design:Relevant studies were retrieved from electronic databases,including PubMed,Cochrane Library,Embase,China National Knowledge Infrastructure,VIP,and WanFang Data,from database inception to June 8,2022.The lev-els of low-density lipoprotein cholesterol,total cholesterol,triglycerides,and high-density lipoprotein cholesterol in patients’serum after treatment were the primary endpoint.Results:Nine randomized controlled trials(2586 patients)met the inclusion criteria.The meta-analysis indi-cated that pitavastatin plus ezetimibe resulted in significantly lower levels of LDL-C[standardized mean difference(SMD)=−0.86,95%confidence interval(CI)(−1.15 to−0.58),P<0.01],TC[SMD=−0.84,95%CI(−1.10 to−0.59),P<0.01],and TG[SMD=−0.59,95%CI(−0.89 to−0.28),P<0.01]than pitavastatin alone.Conclusions:Pitavastatin plus ezetimibe significantly decreased serum LDL-C,TC,and TG levels in patients with CHD.展开更多
Non-alcoholic fatty liver disease (NAFLD) encompasses a histological spectrum ranging from simple steatosis to steatohepatitis,advanced fibrosis and inflammatory changes.Ezetimibe inhibits cholesterol absorption from ...Non-alcoholic fatty liver disease (NAFLD) encompasses a histological spectrum ranging from simple steatosis to steatohepatitis,advanced fibrosis and inflammatory changes.Ezetimibe inhibits cholesterol absorption from the intestinal lumen into enterocytes.The molecular target of ezetimibe is the sterol transporter Niemann-Pick C1-like 1 protein (NPC1L1).Human NPC1L1 is abundantly expressed in the liver and may facilitate the hepatic accumulation of cholesterol.Ezetimibe ex-erts beneficial effects on several metabolic variables.Ezetimibe treatment attenuates hepatic steatosis and is beneficial in terms of NAFLD biochemical markers.The combination of ezetimibe with other interventions may also be beneficial in NAFLD patients.Our group inves-tigated the ezetimibe-orlistat combination treatment in overweight and obese patients with hypercholeste-rolemia,with beneficial effects on NAFLD biochemical markers.These results are promising for patients with NAFLD,who usually have increased cardiovascular disease risk and need a multifactorial treatment.How-ever,it should be mentioned that most results are from animal studies and,although modest elevation of liver function tests may raise the suspicion of NAFLD,none of these tests are sensitive to establish the diagnosis of NAFLD with great accuracy.展开更多
AIM: To investigate whether ezetimibe ameliorates hepatic steatosis and induces autophagy in a rat model of obesity and type 2 diabetes. METHODS: Male age-matched lean control LETO and obese and diabetic OLETF rats we...AIM: To investigate whether ezetimibe ameliorates hepatic steatosis and induces autophagy in a rat model of obesity and type 2 diabetes. METHODS: Male age-matched lean control LETO and obese and diabetic OLETF rats were administered either PBS or ezetimibe(10 mg/kg per day) via stomach gavage for 20 wk. Changes in weight gain and energy intake were regularly monitored. Blood and liver tissue were harvested after overnight fasting at the end of study. Histological assessment was performed in liver tissue. The concentrations of glucose, insulin, triglycerides(TG), free fatty acids(FFA), and total cholesterol(TC) in blood and TG, FFA, and TG in livertissue were measured. m RNA and protein abundance involved in autophagy was analyzed in the liver. To investigate the effect of ezetimibe on autophagy and reduction in hepatic fat accumulation, human Huh7 hepatocytes were incubated with ezetimibe(10 μmol/L) together with or without palmitic acid(PA, 0.5 mmol/L, 24 h). Transmission electron microscopy(TEM) was employed to demonstrate effect of ezetimibe on autophagy formation. Autophagic flux was measured with bafilomycin A1, an inhibitor of autophagy and following immunoblotting for autophagy-related protein expression.RESULTS: In the OLETF rats that received ezetimibe(10 mg/kg per day), liver weight were significantly decreased by 20% compared to OLETF control rats without changes in food intake and body weight(P < 0.05). Lipid parameters including TG, FFA, and TC in liver tissue of ezetimibe-administrated OLETF rats were dramatically decreased at least by 30% compared to OLETF controls(P < 0.01). The serum glucose, insulin, HOMA-IR, and lipid profiles were also improved by ezetimibe(P < 0.05). In addition, autophagy-related m RNA expression including ATG5, ATG6, and ATG7 and the protein level of microtubule-associated protein light chain 3(LC3) were significantly increased in the liver in rats that received ezetimibe(P < 0.05). Likewise, for hepatocytes cultured in vitro, ezetimibe treatment significantly decreased PA-induced fat accumulation and increased PA-reduced m RNA and protein expression involved in autophagy(P < 0.05). Ezetimibe-increased autophagosomes was observed in TEM analysis. Immunoblotting analysis of autophagy formation with an inhibitor of autophagy demonstrated that ezetimibe-increased autophagy resulted from increased autophagic flux. CONCLUSION: The present study demonstrates that ezetimibe-mediated improvement in hepatic steatosis might involve the induction of autophagy.展开更多
A convenient method for the synthesis of ezetimibe analogs as cholesterol absorption inhibitors was described.The key step in the synthesis was the intramolecular ring formation through Mitsunobu reaction.Furthermore,...A convenient method for the synthesis of ezetimibe analogs as cholesterol absorption inhibitors was described.The key step in the synthesis was the intramolecular ring formation through Mitsunobu reaction.Furthermore,a new series of analogs was designed and synthesized.展开更多
A simple and rapid Supercritical Fluid Chromatography (SFC) method has been developed to isolate and characterize R-Isomer of Ezetimi be by using normal phase Chiral Cel OD-H with 250 mm × 30 mm, 5 microns column...A simple and rapid Supercritical Fluid Chromatography (SFC) method has been developed to isolate and characterize R-Isomer of Ezetimi be by using normal phase Chiral Cel OD-H with 250 mm × 30 mm, 5 microns column using a mobile phase system containing super critical fluid carbondi oxide (Co2) and the percentage of 2-Propanol as a mobile phase (85:15) and detection at 230 nm. The isolated R-Isomer is characterized by using UV-vis, FT-IR, ESI-MS, HPLC1H and 13C NMR. The purity of isolated R-Isomer is about 98%.展开更多
A normal phase enantioselective high performance liquid chromatographic method was developed for enantiomeric resolution of Ezetimibe it reduces the overall delivery of cholesterol to the liver. The enantiomers of Eze...A normal phase enantioselective high performance liquid chromatographic method was developed for enantiomeric resolution of Ezetimibe it reduces the overall delivery of cholesterol to the liver. The enantiomers of Ezetimibe were resolved on a Chiral Pak AS-H (250 × 4.6 mm, 5 μm) column using a mobile phase system containing n-Hexane, etha-nol, 2-Propanol and Trifloroacetic acid (84:12:4:0.1 v/v). The resolution between enantiomers was found to be more than 2.0. The limit of detection and limit of quantification of (R)-enantiomer were found to be 0.2 μg/mL and 0.5 μg/mL, respectively, for 10 μL injection volume. The sample solution and mobile phase were found to be stable for at least 48 h. The final optimized method was successfully applied to separate (R)-enantiomer from Ezetimibe and was proven to be reproducible and accurate for the quantitative determination of (R)-enantiomer in bulk drugs.展开更多
Intensive treatment of hyperlipidemia is an important factor in the prevention of cardiovascular disease. Among several therapies, statins are well recognized as playing a central role, although low density lipoprotei...Intensive treatment of hyperlipidemia is an important factor in the prevention of cardiovascular disease. Among several therapies, statins are well recognized as playing a central role, although low density lipoprotein bound cholesterol-apheresis can be used to treat very severe cases of familial hypercholesterolemia. However, statins are not always effective on their own and, recently, ezetimibe has emerged as a unique anti- hypercholesterolemic drug that acts as a cholesterol transporter inhibitor;its role is only partially understood. I experienced rare case that appeared to benefit from ezetimibe therapy, and report them as they help increase our knowledge of this novel drug.展开更多
Objective:To investigate the effect of clopidogrel combined with ezetimibe on cerebral infarction.Methods:110 patients with acute cerebral infarction treated in our hospital from January 2016 to December 2018 were sel...Objective:To investigate the effect of clopidogrel combined with ezetimibe on cerebral infarction.Methods:110 patients with acute cerebral infarction treated in our hospital from January 2016 to December 2018 were selected as study object. The clinical case data were retrospectively analyzed. According to different treatment options, they were divided into the observation group (using clopidogrel combined with ezetimibe,n=41), the control group 1 (treated with clopidogrel,n=39) and the control group 2 (using clopidogrel combined with atorvastatin,n=30). Finally, the serum levels of folic acid (FA), ferritin, troponin I (cTnI), the blood lipid levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG) and internal carotid artery intima-media thickness (IMT) of three groups were compared. The National Institutes of Health Stroke Scale (NIHSS) score, Barthel score and efficacy of three groups were compared. Results: (1) There were no significant differences in the serum levels( FA, ferritin cTnI), the serum lipid levels (HDL-C, LDL-C, TC, TG), IMT, NIHSS scores, and Barthel scores between three groups (P>0.05).mAfter treatment, the FA and HDL-C values of control group 2 were higher than those of the control group 1 (P<0.05), and the observation group increased significantly compared with control group 2 (P<0.05). In addition, the levels of ferritin, cTnI, LDL-C, TC, TG, IMT, NIHSS score and Barthel score in the control group 2 were lower than those in the control group 1 (P<0.05), and the observation group was more significant than the control group 2 (P<0.05). (2) In terms of treatment efficiency, the observation group was the highest, the control group was 2 was the second, and the control group 1 was the lowest (P<0.05);(3) There was no significant difference among three groups (P>0.05).Conclusions:The combination of clopidogrel and ezetimibe in the treatment of cerebral infarction can effectively improve the blood lipid level, promote the metabolism of nerve function and reduce the formation of plaque. This program is safe and effective and worth recommending.展开更多
文摘Objectives:According to the findings of randomized controlled trials,blood lipid levels in patients with coronary heart disease(CHD)can be significantly decreased through a combination of pitavastatin and ezetimibe;however,the effects and clinical applications of this treatment remain controversial.This meta-analysis was aimed at objectively assessing the efficacy and safety of pitavastatin and ezetimibe in lowering blood lipid levels.Design:Relevant studies were retrieved from electronic databases,including PubMed,Cochrane Library,Embase,China National Knowledge Infrastructure,VIP,and WanFang Data,from database inception to June 8,2022.The lev-els of low-density lipoprotein cholesterol,total cholesterol,triglycerides,and high-density lipoprotein cholesterol in patients’serum after treatment were the primary endpoint.Results:Nine randomized controlled trials(2586 patients)met the inclusion criteria.The meta-analysis indi-cated that pitavastatin plus ezetimibe resulted in significantly lower levels of LDL-C[standardized mean difference(SMD)=−0.86,95%confidence interval(CI)(−1.15 to−0.58),P<0.01],TC[SMD=−0.84,95%CI(−1.10 to−0.59),P<0.01],and TG[SMD=−0.59,95%CI(−0.89 to−0.28),P<0.01]than pitavastatin alone.Conclusions:Pitavastatin plus ezetimibe significantly decreased serum LDL-C,TC,and TG levels in patients with CHD.
文摘Non-alcoholic fatty liver disease (NAFLD) encompasses a histological spectrum ranging from simple steatosis to steatohepatitis,advanced fibrosis and inflammatory changes.Ezetimibe inhibits cholesterol absorption from the intestinal lumen into enterocytes.The molecular target of ezetimibe is the sterol transporter Niemann-Pick C1-like 1 protein (NPC1L1).Human NPC1L1 is abundantly expressed in the liver and may facilitate the hepatic accumulation of cholesterol.Ezetimibe ex-erts beneficial effects on several metabolic variables.Ezetimibe treatment attenuates hepatic steatosis and is beneficial in terms of NAFLD biochemical markers.The combination of ezetimibe with other interventions may also be beneficial in NAFLD patients.Our group inves-tigated the ezetimibe-orlistat combination treatment in overweight and obese patients with hypercholeste-rolemia,with beneficial effects on NAFLD biochemical markers.These results are promising for patients with NAFLD,who usually have increased cardiovascular disease risk and need a multifactorial treatment.How-ever,it should be mentioned that most results are from animal studies and,although modest elevation of liver function tests may raise the suspicion of NAFLD,none of these tests are sensitive to establish the diagnosis of NAFLD with great accuracy.
基金Supported by Samsung Biomedical Research Institute,Grant No.SBRI C-B1-111-3National Research Foundation of Korea,No.2012R1A1A2009143/2013027171Korean Diabetes Association(to Park CY,2014S-1)
文摘AIM: To investigate whether ezetimibe ameliorates hepatic steatosis and induces autophagy in a rat model of obesity and type 2 diabetes. METHODS: Male age-matched lean control LETO and obese and diabetic OLETF rats were administered either PBS or ezetimibe(10 mg/kg per day) via stomach gavage for 20 wk. Changes in weight gain and energy intake were regularly monitored. Blood and liver tissue were harvested after overnight fasting at the end of study. Histological assessment was performed in liver tissue. The concentrations of glucose, insulin, triglycerides(TG), free fatty acids(FFA), and total cholesterol(TC) in blood and TG, FFA, and TG in livertissue were measured. m RNA and protein abundance involved in autophagy was analyzed in the liver. To investigate the effect of ezetimibe on autophagy and reduction in hepatic fat accumulation, human Huh7 hepatocytes were incubated with ezetimibe(10 μmol/L) together with or without palmitic acid(PA, 0.5 mmol/L, 24 h). Transmission electron microscopy(TEM) was employed to demonstrate effect of ezetimibe on autophagy formation. Autophagic flux was measured with bafilomycin A1, an inhibitor of autophagy and following immunoblotting for autophagy-related protein expression.RESULTS: In the OLETF rats that received ezetimibe(10 mg/kg per day), liver weight were significantly decreased by 20% compared to OLETF control rats without changes in food intake and body weight(P < 0.05). Lipid parameters including TG, FFA, and TC in liver tissue of ezetimibe-administrated OLETF rats were dramatically decreased at least by 30% compared to OLETF controls(P < 0.01). The serum glucose, insulin, HOMA-IR, and lipid profiles were also improved by ezetimibe(P < 0.05). In addition, autophagy-related m RNA expression including ATG5, ATG6, and ATG7 and the protein level of microtubule-associated protein light chain 3(LC3) were significantly increased in the liver in rats that received ezetimibe(P < 0.05). Likewise, for hepatocytes cultured in vitro, ezetimibe treatment significantly decreased PA-induced fat accumulation and increased PA-reduced m RNA and protein expression involved in autophagy(P < 0.05). Ezetimibe-increased autophagosomes was observed in TEM analysis. Immunoblotting analysis of autophagy formation with an inhibitor of autophagy demonstrated that ezetimibe-increased autophagy resulted from increased autophagic flux. CONCLUSION: The present study demonstrates that ezetimibe-mediated improvement in hepatic steatosis might involve the induction of autophagy.
文摘A convenient method for the synthesis of ezetimibe analogs as cholesterol absorption inhibitors was described.The key step in the synthesis was the intramolecular ring formation through Mitsunobu reaction.Furthermore,a new series of analogs was designed and synthesized.
文摘A simple and rapid Supercritical Fluid Chromatography (SFC) method has been developed to isolate and characterize R-Isomer of Ezetimi be by using normal phase Chiral Cel OD-H with 250 mm × 30 mm, 5 microns column using a mobile phase system containing super critical fluid carbondi oxide (Co2) and the percentage of 2-Propanol as a mobile phase (85:15) and detection at 230 nm. The isolated R-Isomer is characterized by using UV-vis, FT-IR, ESI-MS, HPLC1H and 13C NMR. The purity of isolated R-Isomer is about 98%.
文摘A normal phase enantioselective high performance liquid chromatographic method was developed for enantiomeric resolution of Ezetimibe it reduces the overall delivery of cholesterol to the liver. The enantiomers of Ezetimibe were resolved on a Chiral Pak AS-H (250 × 4.6 mm, 5 μm) column using a mobile phase system containing n-Hexane, etha-nol, 2-Propanol and Trifloroacetic acid (84:12:4:0.1 v/v). The resolution between enantiomers was found to be more than 2.0. The limit of detection and limit of quantification of (R)-enantiomer were found to be 0.2 μg/mL and 0.5 μg/mL, respectively, for 10 μL injection volume. The sample solution and mobile phase were found to be stable for at least 48 h. The final optimized method was successfully applied to separate (R)-enantiomer from Ezetimibe and was proven to be reproducible and accurate for the quantitative determination of (R)-enantiomer in bulk drugs.
文摘Intensive treatment of hyperlipidemia is an important factor in the prevention of cardiovascular disease. Among several therapies, statins are well recognized as playing a central role, although low density lipoprotein bound cholesterol-apheresis can be used to treat very severe cases of familial hypercholesterolemia. However, statins are not always effective on their own and, recently, ezetimibe has emerged as a unique anti- hypercholesterolemic drug that acts as a cholesterol transporter inhibitor;its role is only partially understood. I experienced rare case that appeared to benefit from ezetimibe therapy, and report them as they help increase our knowledge of this novel drug.
基金Health and family planning commission of Hebei province(No.20160211).
文摘Objective:To investigate the effect of clopidogrel combined with ezetimibe on cerebral infarction.Methods:110 patients with acute cerebral infarction treated in our hospital from January 2016 to December 2018 were selected as study object. The clinical case data were retrospectively analyzed. According to different treatment options, they were divided into the observation group (using clopidogrel combined with ezetimibe,n=41), the control group 1 (treated with clopidogrel,n=39) and the control group 2 (using clopidogrel combined with atorvastatin,n=30). Finally, the serum levels of folic acid (FA), ferritin, troponin I (cTnI), the blood lipid levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG) and internal carotid artery intima-media thickness (IMT) of three groups were compared. The National Institutes of Health Stroke Scale (NIHSS) score, Barthel score and efficacy of three groups were compared. Results: (1) There were no significant differences in the serum levels( FA, ferritin cTnI), the serum lipid levels (HDL-C, LDL-C, TC, TG), IMT, NIHSS scores, and Barthel scores between three groups (P>0.05).mAfter treatment, the FA and HDL-C values of control group 2 were higher than those of the control group 1 (P<0.05), and the observation group increased significantly compared with control group 2 (P<0.05). In addition, the levels of ferritin, cTnI, LDL-C, TC, TG, IMT, NIHSS score and Barthel score in the control group 2 were lower than those in the control group 1 (P<0.05), and the observation group was more significant than the control group 2 (P<0.05). (2) In terms of treatment efficiency, the observation group was the highest, the control group was 2 was the second, and the control group 1 was the lowest (P<0.05);(3) There was no significant difference among three groups (P>0.05).Conclusions:The combination of clopidogrel and ezetimibe in the treatment of cerebral infarction can effectively improve the blood lipid level, promote the metabolism of nerve function and reduce the formation of plaque. This program is safe and effective and worth recommending.
