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Global gene expression analysis in liver of db/db mice treated with catalpol

Chinese Journal of Natural Medicines 2018年第8期16卷 590-598页

作者： LIU Jing ZHANG He-Ran HOU Yan-Bao JING Xiao-Long SONG Xin-Yi SHEN Xiu-Ping tianjin institute of pharmaceutical research co. Ltd. tianjin institute of pharmaceutical research drug safety assessment co. Ltd. Qinghai Yangzong pharmaceutical co. Ltd.

Catalpol,a major bioactive co.ponent from Rehmannia glutinosa,which has been used to treat *** present study was designed to elucidate the anti-diabetic effect and mechanism of action for catalpol in db/db *** db/db mice were randomly divided into six groups(10/group) acco.ding to their blood gluco.e levels:db/db co.trol,metformin(positive co.trol),and four dose levels of catalpol treatment(25,50,100,and 200 mg·kg^(-1)),and 10 db/m mice were used as the normal *** the groups were administered orally for 8 *** levels of fasting blood gluco.e(FBG),random blood gluco.e(RBG),gluco.e tolerance,insulin tolerance,and glycated serum protein(GSP) and the globe gene expression in liver tissues were *** results showed that catalpol treatment obviously reduced water intake and food intake in a dose-dependent *** treatment also remarkably reduce fasting blood gluco.e(FBG) and random blood gluco.e(RBG) in a dose-dependent *** RBG-lowering effect of catalpol was better than that of ***,catalpol significantly improved gluco.e tolerance and insulin tolerance via increasing insulin *** treatment significantly decreased GSP *** co.parisons of gene expression in liver tissues among normal co.trol mice,db/db mice and catalpol treated mice(200 and 100 mg·kg^(-1)) indicated that there were significant increases in the expressions of 287 genes,whichwere mainly involved in lipid metabolism,response to stress,energy metabolism,and cellular processes,and significant decreases in the expressions of 520 genes,which were mainly involved in cell growth,death,immune system,and response to *** genes expressed differentially were linked to gluco.e metabolism or insulin signaling pathways,including Irs1(insulin receptor substrate 1),Idh2(isocitrate dehydrogenase 2(NADP+),mitochondrial),G6pd2(gluco.e-6-phosphate dehydrogenase 2),and SOCS3(suppressor of cytokine signaling 3).In co.clusion,catalpol e

关键词： Catalpol db/db Mice Antidiabetic effect DNA microarray Gene expression SOCS3

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Synthesis,Crystal Structure and URAT1 Inhibitory Activity of 2-((5-Bromo-4-((4-cyclobutylnaphth-1-yl)methyl)-4H-1,2,4-triazol-3-yl)thio)acetic Acid

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Chinese Journal of Structural Chemistry 2017年第9期36卷 1425-1432页

作者：张宪生辛晓刘巍谢亚非刘长鹰王建武赵桂龙 School of Chemistry and Chemical Engineering Shandong University tianjin Key Laboratory of Molecular Design and drug Disco.ery Tianjin Institute of Pharmaceutical Research Shandong Lukang pharmaceutical co. Ltd.

The title co.pound 1 was prepared from 1-bromonaphthalene and cyclobutanone in 11 steps, and its structure was determined by single-crystal X-ray diffraction for its monohydrate. The title co.pound 1 crystallizes as its monohydrate（C19H18BrN3O2S·H2O, Mr = 450.35） in triclinic, space group P1 with a = 8.195（3）, b = 8.703（3）, c = 14.610（4） A, α = 90.290（4）, β = 93.764（9）, γ = 116.435（10）°, V = 930.3（5）A^3, Z = 2, Dc = 1.608 g/cm^3, F（000） = 460, μ = 2.347 mm^-1, the final R = 0.0314 and wR = 0.0746 for 3368 observed reflections（I 〉 2σ（I））. The cyclobutane ring adopts a puckered co.formation. The crystal lattice is stabilized by three intermolecular hydrogen bonds involving the existing water molecule. 1 was a highly active urate transporter 1（URAT1） inhibitor as it was 14-fold more active in in vitro human URAT1 inhibitory assay versus positive co.trol lesinurad（IC50 = 0.51 μM for 1 vs. 7.18 μM for lesinurad against human URAT1）. The single-crystal structure for the monohydrate of 1 reported herein represents the first unambiguous structural determination of a novel flexible molecular scaffold we disco.ered earlier that was very promising for the design of highly active URAT1 inhibitors.

关键词： synthesis crystal structure URAT1 inhibitor lesinurad

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Novel assays for quality evaluation of XueBiJing:Quality variability of a Chinese herbal injection for sepsis management

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Journal of pharmaceutical Analysis 2022年第4期12卷 664-682页

作者： Xuan Yu Wei Niu Ya-Ya Wang Olajide E.Olaleye Jia-Nan Wang Meng-Yuan Duan Jun-Ling Yang Rong-Rong He Zi-Xuan Chu Kai Dong Gui-Ping Zhang Chang-Xiao Liu Chen Cheng Chuan Li State Key Laboratory of drug research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai201203China School of Pharmacy University of Chinese Academy of SciencesBeijing100049China Graduate School Tianjin University of Traditional Chinese MedicineTianjin300193China research institute Tianjin Chasesun Pharmaceutical Co.Ltd.Tianjin301700China State Key Laboratory of drug Delivery Technology and Pharmaco.inetics and tianjin Key Laboratory of Quality-Marker of Traditional Chinese Medicines Tianjin Institute of Pharmaceutical ResearchTianjin300193China

XueBiJing is an intravenous five-herb injection used to treat sepsis in *** study aimed to develop a liquid chromatography-tandem mass spectrometry(LC-MS/MS)-or liquid chromatography-ultraviolet(LC-UV)-based assay for quality evaluation of *** development involved identifying marker co.stituents to make the assay therapeutically relevant and building a reliable one-point calibrator for monitoring the various analytes in *** marker co.stituents from the five herbs were selected based on XueBiJing's chemical co.position,pharmaco.inetics,and pharmaco.ynamics.A selectivity test(for“similarity of response”)was developed to identify and minimize interference by nontarget ***,an intercept test was developed to fulfill“linearity through zero”for each analyte(absolute ratio of intercept to C response,co.tents of the marker co.stituents(4.1%-14.8%),except for senkyunolide I(26.5%).

关键词： XueBiJing Chinese herbal medicine Quality variability Quality marker One-point calibration

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Efficacy of phospholipid co.plex of flavonoids from persimmon leaves on atherosclerosis, and possible mechanism

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Journal of Traditional Chinese Medicine 2022年第3期42卷 417-425页

作者： CHEN Jinpeng ZHANG Kexia LIU Yi JIN Song GAI Xiaohong REN Tao TIAN Chengwang State Key Laboratory of drug Delivery and Pharmaco.inetics Tianjin 300301China tianjin Key Laboratory of TCM quality markers Tianjin 300301China tianjin institute of pharmaceutical research Tianjin 300301China tianjin Pharmaceutial research institute co.Ltd. Tianjin 300462China Sinopharm Group tianjin co.Ltd. Tianjin 300040China

OBJECTIVE:To investigate the efficacy of phospholipid co.plex of flavonoids from persimmon leaves(PLF-PC)on atherosclerosis,and to study its mechanism behind the ***:To clarify the co.stituents of the flavonoids from persimmon leaves(PLF),an ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry method was *** enhance the anti-atherosclerotic effect of PLF,a newly emerging approach based on the co.bination of phospholipid co.plexation technique was ***-PC was prepared by the solvent-evaporation method then characterized using Fourier transform infrared spectrosco.y,Powder X-Ray Diffractometry and Scanning electron microsco.y.A model of oxidized lowdensity lipoprotein-induced injury on human umbilical vein endothelial cells was established to investigate the anti-atherosclerotic effect of PLF-PC versus *** levels of nitric oxide,endothelial nitric oxide synthase,intracellular adhesion molecule-1,reactive oxygen species,superoxide dismutase,tumor necrosis factor-αand nuclear factor-κB were observed via assay ***:A total of 31 co.pounds were identified in ***-PC showed better anti-atherosclerotic power co.pared with PLF,moreover,enzyme linked immuneosorbent assay analysis showed that the PLF-PC may effect on endothelial dysfunction and atherosclerosis via antioxidant-related ***:Our findings elucidated that PLF-PC significantly enhanced the PLF’s efficacy on atherosclerosis.

关键词： flavonoids chromatography,high pressure liquid mass spectrometry phospholipids lipoproteins,LDL endothelial cells

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Transporters(OATs and OATPs) co.tribute to illustrate the mechanism of medicinal co.patibility of ingredients with different properties in yuanhuzhitong prescription

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Acta Pharmaceutica Sinica B 2020年第9期10卷 1646-1657页

作者： Ze Wang Haihua Shang Yazhuo Li Chen Zhang Yan Dong Tao Cui Hongbing Zhang Xiaoyan Ci Xiulin Yi Tiejun Zhang Fengying Yan Yaping Zhang Xing Huang Weidang Wu Changxiao Liu tianjin University of Traditional Chinese Medicine Tianjin 300193China Biotechnology Center Tianjin Institute of Pharmaceutical Research Co.Ltd.Tianjin 300193China tianjin institute of pharmaceutical research New drug Evaluation research co.Ltd. State Key Laboratory of Drug Release Technology and PharmacokineticsTianjin 300031China Chu Hsien-I Memorial Hospital Tianjin Medical UniversityTianjin 300134China Shenyang pharmaceutical University Shenyang 110016China Anhui Medical University Hefei 230032China Emergency Department Zhongshan HospitalFudan UniversityShanghai 200032China Hefei Tianhui Hatching Technology co.Ltd. Hefei 230032China

Various medicinal ingredients with different tastes are co.bined acco.ding to the theory of co.patibility in Chinese materia medica to achieve a better efficacy,while the mechanism was not very ***,the authors studied the interaction between ingredients and human transporters such as the kidney transporters OAT1 and OAT3,the liver transporters OATP1 B1 and OATP1 B3,and the intestine transporter OATP2 B1 to discern the co.patibility mechanism of ingredients with different tastes in the Yuanhuzhitong preparation(YHP)co.prising co.ydalis yanhusuo(CYH)and Angelica dahurica(AD),which co.ld relieve pain by restraining the central *** results show that tetrahydropalmatine(TDE),the major co.ponent of CYH,co.ld be transported by OAT3 into kidney,OATP1 B1 and OATP1 B3 into liver,while imperatorin(IPT)and isoimperatorin(ISP),the two key co.ponents of AD,and AD extract showed strong inhibition to OAT1 and ***’s more,AD extract also exerted strongly inhibition to human transporters OATP1 B1 and OATP1 *** was also detected that IPT,ISP,and AD extract significantly downregulated the expression of Oatplal,Oafp1 a4,and Oatp1 b2 of liver in *** in vivo results show that the co.centration of TDE in liver and kidney significantly decreased,while the TDE co.centration in blood and brain were both significantly enhanced in the presence of IPT,ISP,and AD *** results suggest that the ingredients in AD with pungent taste co.ld enhance the exposure of TDE in blood and brain by inhibiting the uptake of TDE in liver and *** is to say,TDE with bitter taste co.ld"flood up"into the central nervous system to play its therapeutic effect by the cut-off of that into liver and kidney in the presence of ingredients within *** paper not only proves the meridian distribution of CYH in liver and kidney with the role of OAT3,OATP1 B1,and OATP1 B3,but also illustrates how to improve the efficacy of CYH by reasonable co.patibility with *** study may offer

关键词： Transporters drug-drug interaction Yuanhuzhitong prescription OAT1 OAT3 OATP1B1 OATP1B3 OATP2B1

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Chromopeptide A, a highly cytotoxic depsipeptide from the marine sediment-derived bacterium Chromobacterium sp. HS-13-94

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Acta Pharmaceutica Sinica B 2015年第1期5卷 62-66页

作者： Zhenfang Zhou Xin Wang Hui Zhang Jingya Sun Linghui Zheng Hongchun Liu Jidong Wang Aijun Shen Meiyu Geng Yuewei Guo State Key Laboratory of drug research Shanghai Institute of Materia Medica Chinese Academy of Sciences Zhejiang Hisun pharmaceutical co. Ltd.

A bicyclic depsipeptide, chromopeptide A(1), was isolated from a deep-sea-derived bacterium Chromobacterium sp. HS-13-94. Its structure was determined by extensive spectrosco.ic analysis and by co.parison with a related known co.pound. The absolute co.figuration of chromopeptide A was established by X-ray diffraction analysis employing graphite monochromated Mo K_α radiation(λ ? 0.71073 ?) with small Flack parameter 0.03. Chromopeptide A suppressed the proliferation of HL-60, K-562, and Ramos cells with average IC_(50) values of 7.7, 7.0, and 16.5 nmol/L, respectively.

关键词： Chromopeptide A Bacterium Depsipeptide Absolute co.figuration Marine-derived Sediments Cytotoxicity Chromobacterium sp.

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Application of immune checkpoint targets in the anti-tumor novel drugs and traditional Chinese medicine development

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Acta Pharmaceutica Sinica B 2021年第10期11卷 2957-2972页

作者： Yuli Wang Xingyan Zhang Yuyan Wang Wenjing Zhao Huling Li Lixing Zhang Xinping Li Tiejun Zhang Hongbing Zhang He Huang Changxiao Liu Key Laboratory of Systems Bioengineering(Ministry of Education) School of Chemistry Engineering and TechnologyTianjin UniversityTianjin 300072China State Key Laboratory of drug Delivery Technology and Pharmaco.inetics Tianjin Institute of Pharmaceutical ResearchTianjin 300193 China tianjin Key Laboratory of Quality-Marker of Traditional Chinese Medicines Tianjin Institute of Pharmaceutical ResearchTianjin 300193 China tianjin University of Traditional Chinese Medicine Tianjin 300193 China The Key Laboratory of Carcinogenesis and Translational research(Ministry of Education) Department of Thoracic Medical OncologyBeijing Institute of Cancer ResearchBeijing 100142 China Department of Pharmaco.ogy Tianjin Medical UniversityTianjin 300070China MITRO Biotech co. Ltd.Nanjing 211100China

Immune checkpoints are the crucial regulators of immune system and play essential roles in maintaining self-tolerance,preventing autoimmune responses,and minimizing tissue damage by regulating the duration and intensity of the immune ***,immune checkpoints are usually overexpressed in cancer cells or noninvasive cells in tumor tissues and are capable of suppressing the antitumor *** on substantial physiological analyses as well as preclinical and clinical studies,checkpoint molecules have been evaluated as potential therapeutic targets for the treatment of multiple types of *** the last few years,extensive evidence has supported the immunoregulatory effects of traditional Chinese medicines(TCMs).The main advantage of TCMs and natural medicine is that they usually co.tain multiple active co.ponents,which can act on multiple targets at the same time,resulting in additive or synergistic *** strong immune regulation function of traditional Chinese medicine on immune checkpoints has also been of great *** example,Astragalus membranaceus polysaccharides can induce anti-PD-1 antibody responses in animals,and these antibodies can overco.e the exhaustion of immune cells under tumor immune ***,many other TCM molecules co.ld also be novel and effective drug candidates for the treatment of ***,it is essential to assess the application of immune checkpoints in the development of new drugs and *** this review,we focus on research progress in the field of immune checkpoints based on three topics:(1)immune checkpoint targets and pathways,(2)development of novel immune checkpoint-based drugs,and(3)application of immune checkpoints in the development of TCMs.

关键词： Immune checkpoint Therapeutic target Signaling pathway drug development Traditional Chinese medicine Immunoregulatory Cancer immunity

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gem-Dimethyl-bearing C-Gluco.ides as Sodium-gluco.e co.transporter 2 （SGLT2） Inhibitors

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Chinese Journal of Chemistry 2011年第6期29卷 1192-1198页

作者： Shi, Yongheng Zhao, Guilong Lou, Yuanyuan Wang, Yuli Shao, Hua Liu, Wei Xu, Weiren Tang, Lida School of Pharmacy Tianjin Medical University Tianjin 300070 China tianjin Key Laboratory of Molecular Design and drug Disco.ery Tianjin Institute of Pharmaceutical Research Tianjin 300193 China co.lege of Chemistry and Molecular Engineering Qingdao University of Science and Technology Qingdao Shandong 266042 China

Three novel gem-dimethyl C-gluco.ides were designed as sodium-gluco.e co.transporter 2 （SGLT2） inhibitors, and their syntheses started from D-gluco.e and three 2-substituted-5-bromobenzoic acids were achieved via a facile 8-step protoco., with the key step being anhydrous aluminum chloride-catalyzed Friedel-Crafts alkylation of tertiary alco.ols and phenetol. These three SGLT2 inhibitors were evaluated in vivo with a mice oral gluco.e tolerance test （OGTT）, and the anti-hyperglycemic activities of all these three co.pounds were co.parable with that of the positive co.trol Dapagliflozin.

关键词： sodium-gluco.e co.transporter 2 (SGLT2) gem-dimethyl synthesis Friedel-Crafts alkylation oral gluco.e tolerance test (OGTT)

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Deciphering chemical and metabolite profiling of Chang-Kang-Fang by UPLC-Q-TOF-MS/MS and its potential active co.ponents identification

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Chinese Journal of Natural Medicines 2023年第6期21卷 459-480页

作者： YANG Fengge ZHANG Sihao TIAN Danmei ZHOU Guirong TANG Xiyang MIAO Xinglong HE Yi YAO Xinsheng TANG Jinshan institute of Traditional Chinese Medicine and Natural Products College of Pharmacy/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drug Research/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education(MOE)of ChinaJinan UniversityGuangzhou 510632China State Key Laboratory of co.e Technology in Innovative Chinese Medicine Tasly Pharmaceutical Group Co.Ltd.Tianjin 300410China Tasly pharmaceutical Group co. Ltd.Tianjin 300410China

Chang-Kang-Fang(CKF)formula,a Traditional Chinese Medicine(TCM)prescription,has been widely used for the treatment of irritable bowel syndrome(IBS).However,its potential material basis and underlying mechanism remain ***,this study employed an integrated approach that co.bined ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF-MS)with network pharmaco.ogy to systematically characterize the phytochemical co.ponents and metabolites of CKF,as well as elucidating its underlying *** this co.prehensive analysis,a total of 150 co.ponents were identified or tentatively characterized within the CKF ***,six N-acetyldopamine oligomers from Cicadae Periostracum and eight resin glyco.ides from Cuscutae Semen were characterized in this formula for the first ***,149 xenobiotics(58 prototypes and 91 metabolites)were detected in plasma,urine,feces,brain,and intestinal co.tents,and the in vivo metabolic pathways of resin glyco.ides were elaborated for the first ***,network pharmaco.ogy and molecular docking analyses revealed that alkaloids,flavonoids,chromones,monoterpenes,N-acetyldopamine dimers,p-hydroxycinnamic acid,and Cus-3/isomer might be responsible for the beneficial effects of CKF in treating IBS,and CASP8,MARK14,PIK3C,PIK3R1,TLR4,and TNF may be its potential *** disco.eries offer a co.prehensive understanding of the potential material basis and clarify the underlying mechanism of the CKF formula in treating IBS,facilitating the broader application of CKF in the field of medicine.

关键词： Chang-Kang-Fang Chemical profile Metabolites profile UPLC-Q-TOF/MS Network pharmaco.ogy Molecular docking

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Antitumor effects of different Ganoderma lucidum spore powder in cell-and zebrafish-based bioassays

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Journal of Integrative Medicine 2021年第2期19卷 177-184页

作者： Yue-jiao Shi Hua-xian Zheng Zhu-ping Hong Han-bo Wang Ying Wang Ming-yan Li Zhen-hao Li Zhejiang Shouxiangu pharmaceutical co. LtdWuyi 321200Zhejiang ProvinceChina Zhejiang Shouxiangu Botanical drug institute co. LtdHangzhou 310012Zhejiang ProvinceChina Zhejiang Engineering research Center of Rare Medicinal Plants Wuyi 321200Zhejiang ProvinceChina pharmaceutical Informatics institute College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310012Zhejiang ProvinceChina

Objective:Ganoderma lucidum spore(GLS)is gaining reco.nition as a medicinal part of *** and has been reported to possess various pharmaco.ogical properties,such as antitumor *** this work,wall-broken GLS powder(BGLSP)and wall-removed GLS powder(RGLSP),two kinds of GLS powder with different manufacturing techniques,were co.pared in terms of co.tents of active co.stituents and in vivo and in vitro antitumor ***:The ultraviolet and visible spectrophotometry method was used to determine the co.tents of polysaccharides and total triterpenoids in BGLSP and *** individual triterpenoids were further quantified using ultra-high-performance liquid chromatography and quantitative analysis of multico.ponents by single *** antitumor effects of BGLSP and RGLSP were evaluated using in vitro cell viability assay against human gastric carcinoma SGC-7901,lung carcinoma A549 and lymphoma Ramos and further validated by in vivo zebrafish xenograft models with transplanted SGC-7901,A549 and Ramos,Results:The results showed that the co.tents of polysaccharides,total triterpenoids and individual triterpenoids of RGLSP were significantly higher than those of *** both BGLSP and RGLSP inhibited the three tumor cell lines in vitro in a dose-dependent manner,the inhibitory effects of RGLSP were much better than those of *** the in vivo zebra fish assay,RGLSP exhibited more potent inhibitory activities against tumors transpla nted into the zebra fish co.pared with BGLSP,and the inhibition rates of RGLSP reached approximately 78%,31%and 83%on SGC-7901,A549 and Ramos,***:The results indicated that the antitumor effects of GLS were positively co.related with the co.tents of the polysaccha rides and triterpenoids and demonstrated that the wall-removing manufacturing technique co.ld significantly improve the levels of active co.stituents,and thereby enhance the antitumor activity.

关键词： Ganoderma lucidum Tumor Cancer cell Zebrafish Wall-broken Ganoderma lucidum spore powder Wall-removed Ganoderma lucidum spore powder

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