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Evaluating the Compatibility Mechanism of Shengxian Decoction Based on an excretion Study of 18 Bioactive Constituents in Rat Biosamples

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World Journal of Traditional Chinese Medicine 2024年第1期10卷 40-52页

作者： Tao Pang Nan Weng Yong Chen Cui-Yun Huang Mei Sun Feng Zhang Wan-Sheng Chen Department of Pharmacy Changzheng HospitalNaval Medical University(Second Military Medical University)ShanghaiChina Department of Pharmacognosy Shenyang Pharmaceutical University ShenyangLiaoning ProvinceChina Traditional Chinese Medicine Resource and Technology Center Shanghai University of Traditional Chinese MedicineShanghaiChina

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.

关键词： Compatibility excretion liquid chromatography coupled with mass spectrometry Platycodonis Radix Shengxian decoction

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Effect of Jiyin Juedu Qiangxin formula on the excretion of water and sodium in rats with cardiorenal syndrome

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China Medical Abstracts(Internal Medicine) 2024年第1期41卷 17-18页

作者：刘成帅 Dept Cardiovasc Guang'anmen HospChina CM AcadBeijing 100053

Objective To observe the effect of Jiyin Juedu Qiangxin Formula (JJQF) on the excretion of water and sodium in cardiorenal syndrome (CRS) rats.Methods The CRS model was established by coronary artery ligation combined with 3/4 nephrectomy.According to the random digit table,totally successfully modeled 30rats were randomly divided into model group.

关键词： excretion rats cardio

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Development and Validation of UHPLC-MS/MS Method for Quantifying of Agarotriose:An Application for Pharmacokinetic,Tissue Distribution,and excretion Studies in Rats

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Journal of Ocean University of China 2023年第6期22卷 1683-1691页

作者： YUE Jiali CHENG Wei WEI Shutong LIU Guilin ZHOU Meichen LV Zhihua YU Mingming School of Medicine and Pharmacy Ocean University of ChinaQingdao 266003China Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology Qingdao 266003China Key Laboratory of Glycoscience&Glycotechnology of Shandong Province Qingdao 266003China Key Laboratory of Marine Drugs Ministry of Education of ChinaQingdao 266003China

A sensitive,rapid,and robust ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)method was established for the first time to quantify agarotriose(A3)in rat plasma,tissues,urine,and feces.A3 and stachyose(internal standard)were separated by a BEH amide column at 65℃under the mobile phase of 10 mmol L^(-1)ammonium ace-tate-acetonitrile(42:58,v/v)with 350µLmin-1.The acquisition of transitions was carried out in multiple reaction monitoring(MRM)pattern operating with positive ionization at m/z 509.16>329.15 for A3 and m/z 689.15>527.11 for stachyose.The linearity ranges of A3 were 10 to 5000nmolL^(-1)for plasma,20 to 10000nmolL^(-1)for tissues,and 40 to 20000nmolL^(-1)for urine and feces.The accuracy and precision ranged from 90.9%to 111.6%and 0.7%to 10.1%,respectively.The stability was between 86.1%and 102.5%.The extraction recovery was consistent and reproducible.The matrix effect ranged from 1.5%to 11.4%.The pharmacokinetic,tissue dis-tribution,and excretion studies were successfully conducted with the validated method.Results showed that A3 could be absorbed by rats,and the absolute bioavailability was 6.7%.Furthermore,it was rapidly distributed in rat tissues and mainly eliminated via feces excretion(67.0%)after oral administration.For intravenous bolus,85.5%was recovered,and renal excretion was the primary path-way(77.6%)for cumulative recovery.

关键词： agarotriose UHPLC-MS/MS pharmacokinetic tissue distribution excretion

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Opportunities and challenges of incretin-based hypoglycemic agents treating type 2 diabetes mellitus from the perspective of physiological disposition

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药学学报:英文版 2023年第6期13卷 2383-2402页

作者： Yaochen Xie Qian Zhou Qiaojun He Xiaoyi Wang Jincheng Wang Center for Drug Safety Evaluation and Research Zhejiang Province Key Laboratory of Anti-Cancer Drug ResearchCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou 310007China Department of Pharmacy Hangzhou Medical CollegeHangzhou 310053China Department of Nephrology the First Affiliated Hospital of Huzhou Teachers Collegethe First People's Hospital of HuzhouHangzhou 313000China

The treatment of patients with diabetes mellitus, which is characterized by defective insulin secretion and/or the inability of tissues to respond to insulin, has been studied for decades. Many studies have focused on the use of incretin-based hypoglycemic agents in treating type 2 diabetes mellitus(T2DM). These drugs are classified as GLP-1 receptor agonists, which mimic the function of GLP-1,and DPP-4 inhibitors, which avoid GLP-1 degradation. Many incretin-based hypoglycemic agents have been approved and are widely used, and their physiological disposition and structural characteristics are crucial in the discovery of more effective drugs and provide guidance for clinical treatment of T2DM.Here, we summarize the functional mechanisms and other information of the drugs that are currently approved or under research for T2DM treatment. In addition, their physiological disposition, including metabolism, excretion, and potential drug drug interactions, is thoroughly reviewed. We also discuss similarities and differences in metabolism and excretion between GLP-1 receptor agonists and DPP-4 inhibitors. This review may facilitate clinical decision making based on patients' physical conditions and the avoidance of drug drug interactions. Moreover, the identification and development of novel drugs with appropriate physiological dispositions might be inspired.

关键词： T2DM Incretins-based hypoglycemic agents GLP-1 receptor agonists DPP-4 inhibitors Physiological disposition Metabolism excretion Drug drug interactions

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Biological fate and interaction with cytochromes P450 of the nanocarrier material,D-α-tocopheryl polyethylene glycol 1000 succinate

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Acta Pharmaceutica Sinica B 2022年第7期12卷 3156-3166页

作者： Tianming Ren Runzhi Li Liqiang Zhao J.Paul Fawcett Dong Sun Jingkai Gu Research Center for Drug Metabolism School of Life SciencesJilin UniversityChangchun 130012China State Key Laboratory of Supramolecular Structure and Materials Jilin UniversityChangchun 130012China Beijing Institute of Drug Metabolism Beijing 102209China

D-a-Tocopheryl polyethylene glycol 1000 succinate(TPGS,also known as vitamin E-TPGS)is a biodegradable amphiphilic polymer prepared by esterification of vitamin E with polyethylene glycol(PEG)1000.It is approved by the US Food and Drug Administration(FDA)and has found wide application in nanocarrier drug delivery systems(NDDS).Fully characterizing the in vivo fate and pharmacokinetic behavior of TPGS is important to promote the further development of TPGS-based NDDS.However,to date,a bioassay for the simultaneous quantitation of TPGS and its metabolite,PEG1000,has not been reported.In the present study,we developed such an innovative bioassay and used it to investigate the pharmacokinetics,tissue distribution and excretion of TPGS and PEG1000 in rat after oral and intravenous dosing.In addition,we evaluated the interaction of TPGS with cytochromes P450(CYP450s)in human liver microsomes.The results show that TPGS is poorly absorbed after oral administration with very low bioavailability and that,after intravenous administration,TPGS and PEG1000 are mainly distributed to the spleen,liver,lung and kidney before both being slowly eliminated in urine and feces as PEG1000.In vitro studies show the inhibition of human CYP450 enzymes by TPGS is limited to a weak inhibition of CYP3A4.Overall,our results provide a clear picture of the in vivo fate of TPGS which will be useful in evaluating the safety of TPGS-based NDDS in clinical use and in promoting their further development.

关键词： TPGS LC-MS/MS Nanocarrier materials Pharmacokinetics Tissue distribution Metabolism excretion Cytochrome P450

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Simultaneous quantification of ginsenoside Rg1 and its metabolites by HPLC–MS/MS:Rg1 excretion in rat bile, urine and feces

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Acta Pharmaceutica Sinica B 2016年第6期6卷 593-599页

作者： Chiyu He Ru Feng Yupeng Sun Shifeng Chu Ji Chen Chao Ma Jie Fu Zhenxiong Zhao Min Huang Jiawen Shou Xiaoyang Li Yuzhu Wang Jinfeng Hu Yan Wang Juntian Zhang State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences Beijing Analytical Application Center Shimadzu (China) Co. Ltd.

Ginsenoside Rg1(Rg1), the major effective component of ginseng, has been shown to have multiple bioactivities, but low oral bioavailability. The aim of this study was to develop a simple, sensitive and rapid high performance liquid chromatography–tandem mass spectrometry(LC–MS/MS) method, which could be used to validate and quantify the concentrations of Rg1 and its metabolites in Sprague-Dawley rat bile,urine, and feces after oral administration(25 mg/kg). Calibration curves offered satisfactory linearity(r40.995)within the determined ranges. Both intra-day and inter-day variances were less than 15%, and the accuracy was within 80–120%. The excretion recoveries of Rg1, ginsenoside Rh1(Rh1), and protopanaxatriol(Ppt) in bile,urine, and feces combined were all greater than 70%. The fecal excretion recoveries of Rg1, Rh1, and Ppt were40.11%, 22.19%, and 22.88%, respectively, whereas 6.88% of Rg1 and 0.09% of Rh1 were excreted in bile.Urinary excretion accounted for only 0.04% of Rg1. In conclusion, the observed excretion profiles for Rg1 and its metabolites after oral administration are helpful for understanding the poor oral bioavailability of Rg1 and will aid further investigations of Rg1 as a pharmacologically active component.

关键词： Ginsenoside Rg1 Ginsenoside Rh1 Protopanaxatriol excretion LC–MS/MS

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Pharmacokinetics,bioavailability,metabolism and excretion of δ-viniferin in rats

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Acta Pharmaceutica Sinica B 2016年第3期6卷 243-252页

作者： Ping Mao Yinping Lei Tingting Zhang Chen Ma Bo Jin Tong Li Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College

A highly rapid and sensitive liquid chromatographic–electrospray ionization tandem mass spectrometric(LC–ESI-MS/MS) method was developed and validated for the determination of trans-δ-viniferin(Rs-1) in rat plasma, urine and feces. All biological samples were prepared by liquid–liquid extraction and hesperetin was included as an internal standard(IS). Chromatographic separation was achieved on a shim-pack XR-ODS column using a gradient mobile phase. MS/MS detection was performed by negative ion electrospray ionization. The method was sensitive with a lower limit of quantification of 1.42 ng/m L and linear over the range of 1.42–2172 ng/m L in all matrices. The method was applied to study the pharmacokinetics, bioavailability, metabolism, and excretion of Rs-1 in rats following a single oral or intravenous dose. Two metabolites, Rs-1 glucuronide and Rs-1 sulfate, were detected in plasma and in urine after administration of Rs-1. The absolute oral bioavailability of Rs-1 was2.3%, and the total absorption rose to 31.5% with addition of its glucuronide and sulfate metabolites. Only0.09% of the gavaged dose, including Rs-1 and metabolites, was excreted in the urine, while 60.3% was found in the feces in unchanged form. The results indicate that both poor absorption and extensive metabolism were the important factors that led to the poor bioavailability of Rs-1, which can provide a basis for further studies on structural modification and dosage form design.

关键词： Viniferin Pharmacokinetics excretion Metabolism Bioavailability LC–MS/MS

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Herb-drug interaction in the protective effect of Alpinia officinarum against gastric injury induced by indomethacin based on pharmacokinetic, tissue distribution and excretion studies in rats

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Journal of Pharmaceutical Analysis 2021年第2期11卷 200-209页

作者： Xuguang Zhang Zhenrui Xie Xun Chen Junqiang Qiu Yinfeng Tan Xiaoliang Li Hailong Li Junqing Zhang Key Laboratory of Tropical Translation Medicine of Ministry of Education Hainan Provincial Key Laboratory for Research and Development of Tropical HerbsSchool of PharmacyHainan Medical UniversityHaikou571199China

Alpinia officinarum Hance of the Chinese traditional herb for the treatment of emesis, abdominal pain and diarrhea has been used to counteract gastric disease induced by indomethacin in rats without obvious side effects. However, the role of herb-drug interaction between indomethacin and A. officinarum based on pharmacokinetic, tissue distribution and excretion still remains unknown. In this study, an ultra-fast liquid-tandem mass spectrometry(UFLC-MS/MS) method was developed for simultaneous determination of indomethacin and its three metabolites, O-desmethylindomethacin(ODI), deschlorobenzoylindomethacin(NDI) and indomethacin acyl-b-D-glucuronide(IDAbG) by oral administration of indomethacin solution with and without the ethanolic extract of A. officinarum and applied to comparative pharmacokinetic, tissue distribution and excretion studies. Our results clarified that oral administration of A. officinarum produced significant alterations in the pharmacokinetic parameters of indomethacin. And the pharmacokinetic interaction between indomethacin and A. officinarum reduced the systemic exposure of indomethacin and increased its elimination. Tissue distribution results demonstrated that co-administration of A. Officinarum could not reduce the accumulation of indomethacin in the target tissue of the stomach, but could accelerate the excretions of indomethacin and its three metabolites including ODI, NDI and IDAb G in the bile and feces of rats in the excretion study.Therefore, A. Officinarum might have a gastrointestinal protective effect through the interaction role with indomethacin based on the pharmacokinetics and excretion in rats.

关键词： Alpinia officinarum Hance Indomethacin Herb-drug interaction Pharmacokinetics Tissue distribution excretion

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Effect of different dietary protein levels and amino acids supplementation patterns on growth performance, carcass characteristics and nitrogen excretion in growing-finishing pigs

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Journal of Animal Science and Biotechnology 2020年第1期11卷 111-120页

作者： Yumei Zhao Gang Tian Daiwen Chen Ping Zheng Jie Yu Jun He Xiangbing Mao Zhiqing Huang Yuheng Luo Junqiu Luo Bing Yu Key Laboratory of Animal Disease-Resistance Nutrition Animal Nutrition InstituteSichuan Agricultural University46#Xinkang RoadYucheng DistrictYaan 625014SichuanChina

Background:This study was conducted to determine the effects of different dietary protein levels and amino acids supplementation patterns in low protein diets on the growth performance,carcass characteristics and nitrogen excretion in growing-finishing pigs.Forty-two barrows(25.00±0.39 kg)were randomly assigned to 7 diets.Diet 1:the high crude protein diet with balanced for 10 essential amino acids(EAAs).Diet 2:the medium crude protein diet with 2%(approx)decreased protein level of Diet 1 and balanced 10 EAAs.Diet 3:the low crude protein diet with 4%decreased protein level of Diet 1 and balanced 10 EAAs.The protein levels of Diet 4,5,6 and 7 were the same as that of Diet 3.Diet 4 was only balanced for lysine(Lys),methionine(Met),threonine(Thr)and tryptophan(Trp);Diet 5 and 6 were further supplemented with extra isoleucine(Ile)or valine(Val),respectively;Diet 7 was further supplemented with extra Ile+Val.Results:Over the 112 days trial,the reduction of dietary protein by 2%or 4%with balanced10 EAAs significantly decreased nitrogen excretion(P0.05).In low protein diet,Val supplementation significantly increased body weight gain at 25–50 kg phase(P0.05).The total N excretion of pigs supplemented with only Lys,Met,Thr and Trp was numerically higher than that of pigs fed with extra Ile,or Val,or Ile+Val diets.Conclusion:In low protein diet,Val is more required than Ile in the early growing phage(25–50 kg),while Ile becomes more required in the late growing and finishing phage(75–125 kg).

关键词： Growing-finishing pigs Growth performance Isoleucine Low protein diets Nitrogen excretion Valine

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Dietary nutrient status modulates nutrient regeneration in the marine ciliate Euplotes vannus

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Acta Oceanologica Sinica 2023年第11期42卷 81-89页

作者： Xuejia He Zhang Lu Weijie Chen Zhen Shi Linjian Ou Ren Hu College of Life Science and Technology and Key Laboratory of Eutrophication and Red Tide Prevention of Guangdong Higher Education Institutes Jinan UniversityGuangzhou 510000China South China Sea Institute of Oceanology Chinese Academy of ScienceGuangzhou 510000China Institute of Hydrobiology Jinan UniversityGuangzhou 510000China

Marine ciliates play important roles not only in linking the microbial loop to the classic pelagic and benthic food chains but also in regenerating nutrients,yet how dietary nutrient imbalance impacts their nutrient regeneration has not been thoroughly addressed.The growth and physiological responses of Euplotes vannus to low dietary nitrogen(LN)and low dietary phosphorus(LP)conditions were studied,with the bacterium Pseudomonas putida as prey.Feeding on LN prey reduced the growth rate of E.vannus.Dietary nutrient limitation changed the types and quantities of nutrient recycling.Feeding on LP prey enhanced dissolved organic carbon excretion but reduced orthophosphate excretion,whereas feeding on LN prey generally resulted in decreases in the excretion rate in all N forms(ammonium,urea,and nitrate).In addition,the proportion of ammonium in regenerated N increased significantly under the LN condition.These findings indicate that a nutrient-imbalanced diet triggers E.vannus to retain limited macronutrients and promotes the recycling of excessive macronutrients,which may potentially form positive and negative feedback to ambient N and P limitations,respectively.

关键词： protist excretion bacteria microbial loop nutrient regeneration

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