Quality control and screening of active substances in traditional Chinese medicines have been performed using fingerprint analysis. The spectrum-effect relationship between chromatography fingerprints and efficacy of ...Quality control and screening of active substances in traditional Chinese medicines have been performed using fingerprint analysis. The spectrum-effect relationship between chromatography fingerprints and efficacy of herbal drugs is considered as a potentially useful method for determining active ingredients in complex mixtures. The study was designed to develop a method for determining the bioactive components of a compound Chinese medicine called Tiefeng based on spectrum-effect relationships between high-performance liquid chromatography （HPLC） fingerprints and anticoccidial activities. Four peaks of the established HPLC fingerprint indicate the main bioactive components of this medicine. In addition, pharrnacodynamic atlas was defined and used to assess the anticoccidial activity of Tiefeng from different sources for the first time. We found that the level of anticoccidial activity of Tiefeng was consistent with the degree of similarity between the pharmacodynamic atlas and chromatogram of any sample. Furthermore, effect of this medicine was related with the main active constituents, along with the origin and the harvesting time.展开更多
Lactate dehydrogenase(LDH),a vital enzyme in anaerobic glycolysis,is closely associated with the survival of parasites.Previous studies of some parasites have shown that LDH exhibits unique physicochemical properties ...Lactate dehydrogenase(LDH),a vital enzyme in anaerobic glycolysis,is closely associated with the survival of parasites.Previous studies of some parasites have shown that LDH exhibits unique physicochemical properties and molecular structures and may be an ideal potential target for diagnosis and drug screening.In this study,we aimed to investigate the effects of acetamizuril,a novel anticoccidial compound,on LDH in the second-generation merozoites of Eimeria tenella(mz-LDH).Quantitative real-time PCR,Western blot,immunofluorescence and enzyme activity assays were each applied to detect the changes of mz-LDH.Our results indicated that the mRNA and protein levels of mz-LDH were reduced upon acetamizuril treatment.Immunolocalization of mz-LDH demonstrated that considerable amount of mz-LDH was distributed around or in the nuclei of second-generation merozoites within the untreated group;in contrast,the acetamizuril-treated group had very low level of mz-LDH.Meanwhile,LDH enzyme activity assay suggested that a decreased LDH enzyme activity in both cytoplasm and nucleus of merozoites in the acetamizuril-treated group.Moreover,the induced apoptosis in second-generation merozoites by the acetamizuril was evaluated by detecting caspase 3 activity,and acetamizuril was found to significantly increase caspase 3 activity.The above findings show that LDH may play an important role in the mediating the activity of acetamizuril against coccidiosis,and further investigation into this aspect might contribute to new light on the pathogenesis of E.tenella during its interaction with acetamizuril.展开更多
Ethanamizuril(EZL) is a novel triazine anticoccidial compound that has high anticoccidial activity in chickens. In order to treat coccidiosis rationally in poultry, a detection method was developed for ethanamizuril i...Ethanamizuril(EZL) is a novel triazine anticoccidial compound that has high anticoccidial activity in chickens. In order to treat coccidiosis rationally in poultry, a detection method was developed for ethanamizuril in broiler plasma, and then the pharmacokinetics studies were performed in broilers after oral administration of different dose levels. Ethanamizuril was administered as single oral doses at low(0.67 mg kgBW), medium(1.33 mg kgBW) and high(6.67 mg kgBW) levels in which the medium dose was that recommended in clinics. Plasma concentrations of ethanamizuril were determined using ultra-high performance liquid chromatography and the data were analyzed with a non-compartmental model. Peak plasma concentrations of ethanamizuril were(2.16±0.57),(3.91±0.71), and(23.71±5.02) mg Lat(5.17±1.80),(4.60±2.12), and(4.60±2.12) h, respectively. The terminal elimination half-lives(t) for ethanamizuril were(10.84±2.59),(10.66±2.47), and(13.34±3.10) h after oral administration at low, medium and high doses, respectively. The areas under the concentrationtime curve(AUC)) were(37.68±6.87),(73.19±9.18), and(485.76±125.10) mg Lh with mean residence times(MRT) of(14.79±3.03),(15.57±3.69), and(20.22±4.01) h at the 3 dosages, respectively. Ethanamizuril was absorbed rapidly and eliminated slowly. A comparison across the dose range indicated that the time to reach peak plasma concentration(T) values were similar while peak plasma concentration(C) and AUCwere positively correlated with increasing dosages. This study of the pharmacokinetics of an ethanamizuril solution in chickens provides a theoretical basis for the rational use in the clinic.展开更多
基金funded by the National Key Technology R&D Program, China (2008 BADB4B05-02)
文摘Quality control and screening of active substances in traditional Chinese medicines have been performed using fingerprint analysis. The spectrum-effect relationship between chromatography fingerprints and efficacy of herbal drugs is considered as a potentially useful method for determining active ingredients in complex mixtures. The study was designed to develop a method for determining the bioactive components of a compound Chinese medicine called Tiefeng based on spectrum-effect relationships between high-performance liquid chromatography （HPLC） fingerprints and anticoccidial activities. Four peaks of the established HPLC fingerprint indicate the main bioactive components of this medicine. In addition, pharrnacodynamic atlas was defined and used to assess the anticoccidial activity of Tiefeng from different sources for the first time. We found that the level of anticoccidial activity of Tiefeng was consistent with the degree of similarity between the pharmacodynamic atlas and chromatogram of any sample. Furthermore, effect of this medicine was related with the main active constituents, along with the origin and the harvesting time.
基金supported by the National Natural Science Foundation of China(31101857,31272607 and 31472235)。
文摘Lactate dehydrogenase(LDH),a vital enzyme in anaerobic glycolysis,is closely associated with the survival of parasites.Previous studies of some parasites have shown that LDH exhibits unique physicochemical properties and molecular structures and may be an ideal potential target for diagnosis and drug screening.In this study,we aimed to investigate the effects of acetamizuril,a novel anticoccidial compound,on LDH in the second-generation merozoites of Eimeria tenella(mz-LDH).Quantitative real-time PCR,Western blot,immunofluorescence and enzyme activity assays were each applied to detect the changes of mz-LDH.Our results indicated that the mRNA and protein levels of mz-LDH were reduced upon acetamizuril treatment.Immunolocalization of mz-LDH demonstrated that considerable amount of mz-LDH was distributed around or in the nuclei of second-generation merozoites within the untreated group;in contrast,the acetamizuril-treated group had very low level of mz-LDH.Meanwhile,LDH enzyme activity assay suggested that a decreased LDH enzyme activity in both cytoplasm and nucleus of merozoites in the acetamizuril-treated group.Moreover,the induced apoptosis in second-generation merozoites by the acetamizuril was evaluated by detecting caspase 3 activity,and acetamizuril was found to significantly increase caspase 3 activity.The above findings show that LDH may play an important role in the mediating the activity of acetamizuril against coccidiosis,and further investigation into this aspect might contribute to new light on the pathogenesis of E.tenella during its interaction with acetamizuril.
基金supported by the National Natural Science Foundation of China (31472235 and 31272607)the Natural Science Foundation of Shanghai, China (14ZR1449000)+2 种基金the Special Scientific Research Fund of Agricultural Public Welfare Profession of China (201303038)the Central Grade Public Welfare Fundamental Science Fund For Scientific Research Institute, China (2016JB08 and 2016JB04)the National Key Technology Research and Development Program of the Ministry of Science and Technology of China (2015BAD11B01-06)
文摘Ethanamizuril(EZL) is a novel triazine anticoccidial compound that has high anticoccidial activity in chickens. In order to treat coccidiosis rationally in poultry, a detection method was developed for ethanamizuril in broiler plasma, and then the pharmacokinetics studies were performed in broilers after oral administration of different dose levels. Ethanamizuril was administered as single oral doses at low(0.67 mg kgBW), medium(1.33 mg kgBW) and high(6.67 mg kgBW) levels in which the medium dose was that recommended in clinics. Plasma concentrations of ethanamizuril were determined using ultra-high performance liquid chromatography and the data were analyzed with a non-compartmental model. Peak plasma concentrations of ethanamizuril were(2.16±0.57),(3.91±0.71), and(23.71±5.02) mg Lat(5.17±1.80),(4.60±2.12), and(4.60±2.12) h, respectively. The terminal elimination half-lives(t) for ethanamizuril were(10.84±2.59),(10.66±2.47), and(13.34±3.10) h after oral administration at low, medium and high doses, respectively. The areas under the concentrationtime curve(AUC)) were(37.68±6.87),(73.19±9.18), and(485.76±125.10) mg Lh with mean residence times(MRT) of(14.79±3.03),(15.57±3.69), and(20.22±4.01) h at the 3 dosages, respectively. Ethanamizuril was absorbed rapidly and eliminated slowly. A comparison across the dose range indicated that the time to reach peak plasma concentration(T) values were similar while peak plasma concentration(C) and AUCwere positively correlated with increasing dosages. This study of the pharmacokinetics of an ethanamizuril solution in chickens provides a theoretical basis for the rational use in the clinic.
