Objective:The study aimed to establish an effective strategy for systematically characterizing and verifying compounds in Huangkui capsules(HKCs).Materials and Methods:An ultrahigh-performance liquid chromatography qu...Objective:The study aimed to establish an effective strategy for systematically characterizing and verifying compounds in Huangkui capsules(HKCs).Materials and Methods:An ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry(MS)method was effectively established and utilized for the chemical compound characterization in HKC,with the support of MS-DIAL,MS-FINDER,and Global Natural Product Social Molecular Network.Multiple rat samples were analyzed after the oral administration.Metabolites were identified based on specific cleavage behaviors,and metabolic pathways were predicted.Semi-quantitative analysis of the metabolome profiles was conducted using post-data processing.High concentrations in vivo were investigated for their role in tacrolimus-induced death of HK-2 cells.Results:In total,129 compounds were identified in HKC,of which 74 were reported for the first time.In this study,we successfully identified and uncovered 19 prototypes and 123 metabolites from the biosamples.The concentrations of glucuronidation and methylation metabolites of quercetin were the highest in the kidney and intestinal tissues.In contrast,significant glucuronidation of quercetin metabolites was observed with high blood concentrations.Notably,quercetin glucuronidation and methylation metabolites protected HK-cell against tacrolimus-induced injury in a dose-dependent manner.Conclusions:This study successfully established a reliable and efficient strategy for comprehensive characterization of traditional Chinese medicine compounds.This strategy harnessed the power of various intelligent postprocessing technologies to provide a more thorough understanding of active components and their metabolic transformations in the body.These results suggest that quercetin metabolites should be evaluated for their protective capacity against kidney disease.展开更多
Introduction:The Shengxian decoction(SXT),a Chinese herbal medication used to treat heart failure,is composed of Astragali Radix,Anemarrhenae Rhizoma,Bupleuri Radix,Cimicifuage Rhizoma,and Platycodonis Radix.Knowledge...Introduction:The Shengxian decoction(SXT),a Chinese herbal medication used to treat heart failure,is composed of Astragali Radix,Anemarrhenae Rhizoma,Bupleuri Radix,Cimicifuage Rhizoma,and Platycodonis Radix.Knowledge of the excretion of the active compounds in this herbal medication is vital for investigating the underlying mechanisms behind its compatibility.However,this remains unclear.Methods:Liquid chromatography coupled with mass spectrometry was performed in both positive and negative modes to assay 18 constituents of SXT from rat urinary,fecal,and biliary samples.Results:The methodology was validated and showed good linearity(r≥0.9),precision,stability,repeatability,and recovery.The relative standard deviations and relative errors for the precision and accuracy did not exceed 15%.The recoveries of all the compounds ranged from 77.37%to 114.82%,and the matrix effect was between 82.53%and 105.71%.The results suggested that,when combined with Platycodonis Radix,the levels of 14 constituents from the four herbs were reduced in the urine,while the levels of six constituents were reduced in the feces.Conclusions:The comparative excretion results indicated that Platycodonis Radix reduced the excretion of compounds in SXT,demonstrating the compatibility mechanism and holistic properties of these compounds,favoring the pharmacological effects of SXT.展开更多
基金supported by the National Natural Science Foundation of China(82274059)the Science and Technology Commission of Shanghai Municipality(22S21901900)+1 种基金the Shanghai Municipal Health Commission(ZYCC2019018)the Jin-Zi-Ta Talent Project(0806 and 1016)。
文摘Objective:The study aimed to establish an effective strategy for systematically characterizing and verifying compounds in Huangkui capsules(HKCs).Materials and Methods:An ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry(MS)method was effectively established and utilized for the chemical compound characterization in HKC,with the support of MS-DIAL,MS-FINDER,and Global Natural Product Social Molecular Network.Multiple rat samples were analyzed after the oral administration.Metabolites were identified based on specific cleavage behaviors,and metabolic pathways were predicted.Semi-quantitative analysis of the metabolome profiles was conducted using post-data processing.High concentrations in vivo were investigated for their role in tacrolimus-induced death of HK-2 cells.Results:In total,129 compounds were identified in HKC,of which 74 were reported for the first time.In this study,we successfully identified and uncovered 19 prototypes and 123 metabolites from the biosamples.The concentrations of glucuronidation and methylation metabolites of quercetin were the highest in the kidney and intestinal tissues.In contrast,significant glucuronidation of quercetin metabolites was observed with high blood concentrations.Notably,quercetin glucuronidation and methylation metabolites protected HK-cell against tacrolimus-induced injury in a dose-dependent manner.Conclusions:This study successfully established a reliable and efficient strategy for comprehensive characterization of traditional Chinese medicine compounds.This strategy harnessed the power of various intelligent postprocessing technologies to provide a more thorough understanding of active components and their metabolic transformations in the body.These results suggest that quercetin metabolites should be evaluated for their protective capacity against kidney disease.
基金supported by National Key R&D Program of China(2022YFC3501700)National Natural Science Foundation of China(82274059)+1 种基金Science and Technology Commission of Shanghai Municipality(22S21901900)Organizational Key Research and Development Program of Shanghai University of Traditional Chinese Medicine(2023YZZ02)。
文摘Introduction:The Shengxian decoction(SXT),a Chinese herbal medication used to treat heart failure,is composed of Astragali Radix,Anemarrhenae Rhizoma,Bupleuri Radix,Cimicifuage Rhizoma,and Platycodonis Radix.Knowledge of the excretion of the active compounds in this herbal medication is vital for investigating the underlying mechanisms behind its compatibility.However,this remains unclear.Methods:Liquid chromatography coupled with mass spectrometry was performed in both positive and negative modes to assay 18 constituents of SXT from rat urinary,fecal,and biliary samples.Results:The methodology was validated and showed good linearity(r≥0.9),precision,stability,repeatability,and recovery.The relative standard deviations and relative errors for the precision and accuracy did not exceed 15%.The recoveries of all the compounds ranged from 77.37%to 114.82%,and the matrix effect was between 82.53%and 105.71%.The results suggested that,when combined with Platycodonis Radix,the levels of 14 constituents from the four herbs were reduced in the urine,while the levels of six constituents were reduced in the feces.Conclusions:The comparative excretion results indicated that Platycodonis Radix reduced the excretion of compounds in SXT,demonstrating the compatibility mechanism and holistic properties of these compounds,favoring the pharmacological effects of SXT.
