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Simultaneous Analysis of Thirteen Bioactive Components in Evodia rutaecarpa and Its Varieties by HPLC-DAD-MS

Chinese Herbal Medicines 2010年第2期2卷 112-117,131页

作者： XU Hai-yu1,3,ZHANG Tie-jun2,XIAO Xue-feng1,ZHAO Ping1,LIU Chang-xiao3,XU Jun2 1.Tianjin University of Traditional Chinese Medicine,Tianjin 300193,China 2.Tianjin Engineering laboratory of Quality Control Techniques for TCM,Tianjin Institute of Pharmaceutical Research,Tianjin 300193,China 3.The National laboratory of Pharmacodynamics and pharmacokinetics,Tianjin Institute of Pharmaceutical Research,Tianjin 300193,China Tianjin University of Traditional Chinese Medicine Tianjin 300193China The National laboratory of Pharmacodynamics and pharmacokinetics Tianjin Institute of Pharmaceutical ResearchTianjin 300193China Tianjin Engineering laboratory of Quality Control Techniques for TCM Tianjin Institute of Pharmaceutical ResearchTianjin 300193China Tianjin University of Traditional Chinese Medicine Tianjin 300193China The National laboratory of Pharmacodynamics and pharmacokinetics Tianjin Institute of Pharmaceutical ResearchTianjin 300193China

Objective To control the quality of Evodia rutaecarpa *** An HPLC-DAD-MS/MS method was established for the rapid and efficient identification of bioactive constituents and for simultaneous quantitative analysis of four bioactive ingredients including evodiamine,rutaecarpine,dehydroevodiamine,and evodin in ***,which was applied to evaluating eight samples of *** and its varieties from different *** Thirteen potentially bioactive constituents including one flavonoid glycoside,one limonin,four indoloquinazoline alkaloids,and seven quinolone alkaloids were identified in all samples and the contents of dehydroevodiamine,evodine,evodiamine,and rutaecarpine varied widely from 0.10% to 0.51%,0.49% to 3.12%,0.07% to 1.56%,and 0.10% to 0.69%,*** This method is found to be convenient,fast,accurate,and it is facilitated to improve the quality control standard of *** and related products.

关键词： dehydroevodiamine Evodia rutaecarpa evodiamine evodin HPLC-DAD-MS rutaecarpine

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Effects of Astragaloside Ⅳ Derivative on Heart Failure in Rats

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Chinese Herbal Medicines 2010年第1期2卷 48-53页

作者： WANG Wei-ting1,ZHAO Zhuan-you1,HAN Ying-mei2,XU Wei-ren2,TANG Li-da1 1.State Key laboratory of pharmacokinetics and Pharmacodynamics,Tianjin Institute of Pharmaceutical Research,Tianjin 300193,China 2.Tianjin Key laboratory of Molecular Design & Drug Discovery,Tianjin Institute of Pharmaceutical Research,Tianjin 300193,China State Key laboratory of pharmacokinetics and Pharmacodynamics Tianjin Institute of Pharmaceutical Research Tianjin300193 China Tianjin Key laboratory of Molecular Design & Drug Discovery Tianjin Institute of Pharmaceutical Research Tianjin 300193China

Objective Astragaloside Ⅳ derivative(ASId) is one of Astragaloside Ⅳ(ASI) derivatives with higher water-solubility and may have more druggability than *** present study aims at observing the effects of ASId on cardiovascular parameters in chronic heart failure in *** Using echocardiographic and haemodynamic measurements,the effects of ASId on congestive heart failure(CHF) induced by ligation of the left coronary artery in rats were *** ASId iv 0.5,1.0,and 2.0 mg/(kg·d) attenuated the decline of ejection *** peak derivatives of the left ventricle(LV) pressure(dp/dt) in ASId treated groups were significantly *** LV volumes in diastole and in systole were decreased significantly after ASId treatment,accompanied with a trend towards normalization of relative wall thickness at *** 0.5,1.0,and 2.0 mg/(kg·d) attenuated the increase of LV systolic and diastolic wall *** treatment also inhibited compensatory hypertrophy of depressed *** ASId could improve cardiac functions and inhibite compensatory hypertrophy and LV remodelling,which suggests the possibility of ASId as a new therapeutic drug for the treatment of CHF.

关键词： astragaloside IV derivative heart failure rat

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pharmacokinetics and Bioequivalence of Dienogest in Healthy Bangladeshi Female Volunteers: An Open-Label, Single-Dose, Randomized, Two-Way Crossover Study

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Open Journal of Obstetrics and Gynecology 2024年第5期14卷 779-789页

作者： Nusrat Mahmud Nafisa Ahamed Uttom Kumar Bhowmik Sabrina Akter Tushi Nayan Ghosh Nithon Chandra Sahana Arifa Akram Md. Alimur Reza BIRDEM General Hospital Dhaka Bangladesh Medical College for Women & Hospital Dhaka Bangladesh Novus Clinical Research Services Ltd. Dhaka Bangladesh National Institute of laboratory Medicine & Referral Centre (NILMRC) Dhaka Bangladesh

Background: Dienogest is a potential treatment for pelvic pain associated with endometriosis, a condition of significant concern in gynaecology. The current study was conducted as a crossover-randomized bioequivalence assessment of two oral Dienogest 2 mg formulations, aiming to provide valuable insights for healthcare professionals and researchers in this field. Objective: The primary aim of this research was to evaluate and compare the pharmacokinetic characteristics of Dienogest 2 mg tablets. Dinogest (Dienogest 2 mg) tablets, manufactured by Nuvista Pharma Limited in Bangladesh, and Visanne (Dienogest 2 mg) tablets, manufactured by Bayer Pharma in Germany, were the test and reference formulations, respectively. Materials and Method: The study was an open-label, balanced, randomized, two treatments, two sequences, two periods, two-way crossover, laboratory blind, single oral dose bioequivalence study conducted in healthy adult females under fasting conditions. The study was carried out on 13 healthy, non-pregnant female subjects, and all the subjects completed both study periods with a 15-day washout in between. Randomization was used to assign the test and reference formulations to the subjects. Following each oral administration, a series of blood samples were obtained at different time intervals from pre-dose to 72 hours post-dose and analyzed for Dienogest concentrations using a validated bio-analytical method. A standard non-compartmental model was used to analyze the pharmacokinetic parameters. The primary pharmacokinetic parameters were peak plasma drug concentration (Cmax), the area under the plasma concentration-time curve from time zero to time t (AUC0–t), and AUC from t = 0 to infinity (AUC0–∞). The other PK parameters included time to reach Cmax (Tmax), terminal elimination rate constant (Kel), and half-life (t1/2). Result: The ratios and 90% CI for the geometric mean test/re

关键词： Dienogest Bioequivalence Study Endometriosis Novus CRSL

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Molecular mechanisms of anti-cancer bioactivities of seaweed polysaccharides

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Chinese Herbal Medicines 2022年第4期14卷 528-534页

作者： Tingting Liu Qing Li Xu Xu Guoxia Li Chengwang Tian Tiejun Zhang School of Basic Medicine Tianjin Medical UniversityTianjin 300070China Tianjin Pharmaceutical Research Institute Tianjin 300462China State Key laboratory of Drug Release Technology and pharmacokinetics Tianjin 300462China Research Unit for Drug Metabolism Chinese Academy of Medical SciencesTianjin 300462China

Seaweed is a traditional Chinese medicine homologous to food,in which polysaccharides are responsible for anti-cancer by enhancing immunity,inducing cancer cell apoptosis,inhibiting cancer cell invasion and metastasis or directly scavenging oxidative free radicals that induce cancer cell *** them,regulating immunity and promoting cancer cell apoptosis are intensively studied due to the important role in preventing *** we reviewed seaweed in the apoptosis-inducing signaling pathways including PI3K/AKT,ROS and JNK and discussed challenges in studying seaweed.

关键词： anti-cancer apoptosis immunomodulation seaweed polysaccharides signal pathways

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Rational design of a nonclassical liposomal nanoscale drug delivery system for innovative cancer therapy

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BMEMat(BioMedical Engineering Materials) 2024年第3期2卷 51-73页

作者： Chunjie Wang Xiaoqi Sun Liangzhu Feng Zhuang Liu Institute of Functional Nano&Soft Materials(FUNSOM) Jiangsu Key Laboratory for Carbon-Based Functional Materials&DevicesSoochow UniversitySuzhouChina Department of Pharmaceutical Sciences University of MichiganAnn ArborUSA

Advanced drug delivery systems are widely considered to be powerful approaches for treating cancer and many other diseases because of their superior ability to improve pharmacokinetics,promote lesion-targeted delivery efficacy,and/or reduce the toxic effects of diverse *** to the unique biomimetic structure of lipid bilayers surrounding aqueous cavities,liposomes have been found to encapsulate various therapeutics,ranging from small molecules with different hydrophobicities to *** the advent of surface PEGylation,stealth liposomes with excellent in vivo long-circulating behaviors have been generated,thus these liposomes have been extensively explored for the development of liposomal drugs with greatly improved in vivo pharmacokinetic behaviors by functioning as delivery *** by their successes in clinical practice,stealth liposomes have recently been utilized as the main building scaffold or surface coating layers of other nanoparticulate formulations,which are coined as nonclassical liposomal nanoscale drug delivery systems(NDDSs)in this review,to enable the rational design of nextgeneration liposomal ***,after overviewing the latest progress in the development of conventional liposome-based nanomedicine,we will introduce the development of these nonclassical liposomal NDDSs as well as their innovative cancer treatment *** will subsequently provide a critical perspective on the future development of new cancer nanomedicines based on these rationally designed nonclassical liposomal NDDSs.

关键词： cancer therapy drug delivery lipid bilayer nonclassical liposomal nanoparticles

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Quantitative Metabolomics:Analysis on Active Components in Extracts from Kaki Folium

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Chinese Herbal Medicines 2012年第4期4卷 276-281页

作者： DAI Li-peng GU Yuan YIN Ren-jie LIU Chang-xiao SI Duan-yun State Key laboratory of Drug Delivery Technology and pharmacokinetics Tianjin Institute of Pharmaceutical Research Tianjin 300193 China School of Chemical Engineering and Technology Tianjin University Tianjin 300072 China Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Co. Ltd. Guangzhou 510515 China

Objective In order to analyze the active components in the extracts from Kaki Folium(KF),quantitative metabolomics approach was adopted to investigate the number of active components existing among the different extracts and their *** LC-MS method was established for the quantitative determination of the active components taking the mixture with reference substance as tested *** In terms of the number of active components and amount presented in the different tested samples of KF extracted by many types of solvents,variation was *** rutin,astragalin,and kaempferol were presented in all *** was found between the samples extracted from the products on market and from the raw materials of KF processed by polar solvents with different ***,the three active components were found in all samples *** These results might be valuable as all information and could be used for the optimization of raw materials extraction procedure to enhance the productivity.

关键词： active components astragalin extracts from Kaki Folium kaempferol metabolomics quantitative metabolomics rutin

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FOXO3 mutation predicting gefitinib-induced hepatotoxicity in NSCLC patients through regulation of autophagy

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Acta Pharmaceutica Sinica B 2022年第9期12卷 3639-3649页

作者： Shaoxing Guan Xi Chen Youhao Chen Guohui Wan Qibiao Su Heng Liang Yunpeng Yang Wenfeng Fang Yan Huang Hongyun Zhao Wei Zhuang Shu Liu Fei Wang Wei Feng Xiaoxu Zhang Min Huang Xueding Wang Li Zhang laboratory of Drug Metabolism and pharmacokinetics School of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510060China State Key laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhou 510060China College of Health Science Guangdong Pharmaceutical UniversityGuangzhou 510006China Sun Yat-sen Memorial Hospital Sun Yat-sen UniversityGuangzhou 510080China Ersha Department of Pharmacy the Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510105China

Hepatotoxicity is a common side effect for patients treated with gefitinib,but the related pathogenesis is unclear and lacks effective predictor and management strategies.A multi-omics approach integrating pharmacometabolomics,pharmacokinetics and pharmacogenomics was employed in non-small cell lung cancer patients to identify the effective predictor for gefitinib-induced hepatotoxicity and explore optional therapy ***,we found that patients with rs4946935 AA,located in Forkhead Box O3(FOXO3)which is a well-known autophagic regulator,had a higher risk of hepatotoxicity than those with the GA or GG variant(OR=18.020,95%CI=2.473 to 459.1784,P=0.018)in a gefitinib-concentration dependent ***,functional experiments identified that rs4946935_A impaired the expression of FOXO3 by inhibiting the promotor activity,increasing the threshold of autophagy initiation and inhibiting the autophagic activity which contributed to gefitinib-induced liver *** contrast,erlotinib-induced liver injury was independent on the variant and expression levels of *** study reveals that FOXO3 mutation,leading to autophagic imbalance,plays important role in gefitinib-induced hepatotoxicity,especially for patients with high concentration of *** conclusion,FOXO3 mutation is an effective predictor and erlotinib might be an appropriately and well-tolerated treatment option for patients carrying rs4946935 AA.

关键词： Gefitinib Hepatotoxicity Pharmacometabolomic pharmacokinetics Pharmacogenomics FOXO3 Autophagy

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A time-released osmotic pump fabricated by compression-coated method: Formulation screen, mechanism research and pharmacokinetic study

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Asian Journal of Pharmaceutical Sciences 2014年第4期9卷 208-217页

作者： Tiegang Xin Yang Zhao Hengpan Jing Wenji Zhang Yunyun Gao Xinggang Yang Xukai Qu Weisan Pan Department of Pharmaceutics School of PharmacyShenyang Pharmaceutical University103 Wenhua RoadShenyang 110016China College of Pharmaceutical Science Zhejiang University of Technology18 Chaowang RoadHangzhou 310014China State Key laboratory of Drug Delivery Technology and pharmacokinetics Tianjin Institute of Pharmaceutical ResearchTianjin 300193China

In this investigation,time-released monolithic osmotic pump(TMOP)tablets containing diltiazem hydrochloride(DIL)were prepared on the basis of osmotic pumping *** developed dosage forms were coated by Kollidon®SR-Polyethylene Glycol(PEG)mixtures via compression-coated technology instead of spray-coating method to form the outer *** more efficient formulation screening,a three-factor five-level central composite design(CCD)was introduced to explore the optimal TMOP formulation during the *** in vitro tests showed that the optimized formulation of DIL-loaded TMOP had a lag time of 4 h and a following 20-h drug release at an approximate zero-order ***,the releasemechanismwas proven based on osmotic pressure and its profile could be well simulated by a dynamic *** oral administration by beagle dogs,the comparison of parameters with the TMOP tablets and reference preparations show no significant differences for C_(max)(111.56±20.42,128.38±29.46 ng/ml)and AUC_(0-48 h)(1654.97±283.77,1625.10±313.58 ng h/ml)but show significant differences for T_(max)(13.00±1.16,4.00±0.82 h).These pharmacokinetic parameters were consistent with the dissolution tests that the TMOP tablets had turned out to prolong the lag time of DIL release.

关键词： Time-released Osmotic pump Compression-coated Central composite design Pharmacokinetic

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pharmacokinetics of the prototype and hydrolyzed carboxylic forms of ginkgolides A, B, and K administered as a ginkgo diterpene lactones meglumine injection in beagle dogs

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Chinese Journal of Natural Medicines 2017年第10期15卷 775-784页

作者： WANG Shu-Yao A Ji-Ye FEI Fei GENG Jian-Liang PENG Ying OUYANG Bing-Chen WANG Pei JIN Xiao-Liang ZHAO Yu-Qing WANG Jian-Kun GENG Ting LI Yan-Jing HUA NG Wen-Zhe WANG Zhen-Zhong XIAO Wei WANG Guang-Ji School of Chinese Pharmacy Beijing University of Chinese Medicine Beijing 100102 China Jiangsu Kanion Modern Chinese Medicine Institute Nanjing 210017 China State Key Labonatory of Pharmaceutical New-Techfor Chinese Medicine Jiangsu Kanion Pharmaceutical Co. Ltd. Lianyungang222001 China Key Lab of Drug Metabolism and pharmacokinetics State Key laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009 China

Ginkgo diterpene lactones meglumine injection(GDLI)is a commercially available product used for ***,the pharmacokinetic properties of the prototypes and hydrolyzed carboxylic forms of the primary components in GDLI,i.e.,ginkgolide A(GA),ginkgolide B(GB),and ginkgolide K(GK),have never been fully evaluated in beagle *** this work,a simple,sensitive,and reliable method based on ultra-fast liquid chromatography-tandem mass spectrometry(UFLC-MS/MS)was developed,and the prototypes and total amounts of GA,GB,and GK were determined in beagle dog *** plasma concentrations of the hydrolyzed carboxylic forms were calculated by subtracting the prototype concentrations from the total lactone *** the first time,the pharmacokinetics of GA,GB,and GK were fully assessed in three forms,i.e.,the prototypes,the hydrolyzed carboxylic forms,and the total amounts,after intravenous administration of GDLI in beagle *** was shown that ginkgolides primarily existed in the hydrolyzed form in plasma,and the ratio of hydrolysates to prototype forms of GA and GB decreased gradually to a homeostatic *** of the three forms of the three ginkgolides showed linear exposure of AUC to the ***,GB,and GK showed a constant half-life approximately 2.7,3.4,and 1.2 h,respectively,which were consistent for the forms at three dose levels(0.3,1.0,and 3.0 mg·kg^(-1))and after a consecutive injection of GDLI for 7 days(1.0 mg·kg^(-1)).

关键词： Hydrolysates of ginkgolides LC-MS/MS pharmacokinetics Ginkgo diterpene lactones Beagle dog

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Discovery of the radio-protecting effect of Ecliptae Herba,its constituents and targeting p53-mediated apoptosis in vitro and in vivo

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Acta Pharmaceutica Sinica B 2023年第6期13卷 1216-1230页

作者： Jiang Wu Wenfeng Gou Zhiyun Wang Huajie Chang Deguan Li Wenbin Hou Changxiao Liu Department of Pharmaceutical Engineering School of Chemical Engineering and TechnologyTianjin UniversityTianjin 300072China Institute of Radiation Medicine Chinese Academy of Medical SciencesTianjin 300192China School of Chinese Materia Medica Tianjin University of Traditional Chinese MedicineTianjin 301617China Research Center for New Drug Evaluation the State Laboratory of Drug Delivery Technology and PharmacokineticsTianjin Institute of Pharmaceutical ResearchTianjin 300193China

Radiation protection drugs are often accompanied by toxicity,even amifostine,which has been the dominant radio-protecting drug for nearly 30 ***,there is no therapeutic drug for radiation-induced intestinal injury(RⅢ).This paper intends to find a safe and effective radioprotecting ingredient from natural *** radio-protecting effect of Ecliptae Herba(EHE) was discovered preliminarily by antioxidant experiments and the mouse survival rate after137Cs *** components and blood substances in vivo were identified through *** correlation network of “natural components in EHE-constituents migrating to blood-targets-pathways” was established to predict the active components and *** binding force between potential active components and targets was studied by molecular docking,and the mechanism was further analyzed by Western blotting,cellular thermal shift assay(CETSA),and Ch ***,the expression levels of Lgr5,Axin2,Ki67,lysozyme,caspase-3,caspase-8,8-OHd G,and p53 in the small intestine of mice were *** was found for the first time that EHE is active in radiation protection and that luteolin is the material basis of this *** is a promising candidate for RⅢ.Luteolin can inhibit the p53 signaling pathway and regulate the BAX/BCL2 ratio in the process of *** could also regulate the expression of multitarget proteins related to the same cell cycle.

关键词： p53 Apoptosis Luteolin Eclipta prostrata L. Radio-protecting Radiation-induced intestinal injury Radiation protection

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