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Bile acid nuclear receptor FXR and digestive system diseases

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Acta Pharmaceutica Sinica B 2015年第2期5卷 135-144页

作者： Lili Ding Li Yang zhengtao wang Wendong Huang Shanghai Key Laboratory of Complex Prescriptions and MOE Key Laboratory for Standardization of Chinese Medicines Institute of Chinese Materia Medica Shanghai University of Traditional Chinese Medicine Department of Diabetes and Metabolic Diseases Research Beckman Research Institute City of Hope National Medical Center

Bile acids (BAs) are not only digestive surfactants but also important cell signaling molecules, which stimulate several signaling pathways to regulate some important biological processes. The bile-acid-activated nuclear receptor, farnesoid X receptor (FXR), plays a pivotal role in regulating bile acid, lipid and glucose homeostasis as well as in regulating the inflammatory responses, harrier function and prevention of bacterial manslocation in the intestinal tract. As expected, FXR is involved in the pathophysiology of a wide, range of diseases of gastrointestinal tract, including inflammatory bowel disease, colorectal cancer and type 2 diabetes. In this review, we discuss current knowledge of the roles of FXR in physiology of the digestive system and the related diseases. Better understanding of the roles of FXR in digestive system will accelerate the development of FXR ligands/modulators for the treatment of digestive system diseases. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. All rights reserved

关键词： Bile acids Farnesoid X receptors Gastrointestinal tract Inflammatory bowel disease Colorectal cancer Type 2 diabetes

Using satellite altimetry leveling to assess the marine geoid

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Geodesy and Geodynamics 2020年第2期11卷 106-111页

作者： zhengtao wang Nengfang Chao Dingbo Chao School of Geodesy and Geomatics Wuhan UniversityWuhan 430079China College of Marine Science and Technology China University of GeosciencesWuhan 430074China

Based on the concept of Global Position System(GPS)/leveling,the satellite altimetry leveling(SAL) is first proposed to evaluate the marine *** is derived by the difference among the mean sea surface(MSS),mean dynamic ocean topography(MDT),and leveling *** this study,(1) the original satellite altimetry data are processed to infer the vertical deflection and gravity anomaly,(2) the Chinese coastal marine geoids(CMG) are determined by using the differe nt methods(including Molodensky,least square collocation,Stokes formula,and two-dimensional fast Fourier transformation(FFT) with the vertical deflection and gravity anomaly data),(3) CMG are evaluated by using the results from above different methods,the Gravity field and steady-state Ocean Circulation Explorer(GOCE) gravity potential model(GGPM),and *** results show that(1) CMG from the Molodensky method has the highest precision by using vertical de flection data,(2) the accuracy of CMG indicate good consistency between the SAL and GGPM,(3) SAL can be used as a new method for assessing marine geoid.

关键词： Satellite altimetry leveling Marine geoid Vertical deflection Gravity anomaly

Astragaloside Ⅳ suppresses post-ischemic natural killer cell infiltration and activation in the brain:involvement of histone deacetylase inhibition

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Frontiers of Medicine 2021年第1期15卷 79-90页

作者： Baokai Dou Shichun Li Luyao Wei Lixin wang Shiguo Zhu zhengtao wang Zunji Ke Kaixian Chen Zhifei wang School of Basic Medical Sciences Shanghai University of Traditional Chinese MedicineShanghai 201203China Institute of Chinese Materia Medica Shanghai University of Traditional Chinese MedicineShanghai 201203China Academy of Integrative Medicine Shanghai University of Traditional Chinese MedicineShanghai 201203China

Natural killer(NK)cells,a type of cytotoxic lymphocytes,can infiltrate into ischemic brain and exacerbate neuronal cell *** Ⅳ(ASIV)is the major bioactive ingredient of Astragalus membranaceus,a Chinese herbal medicine,and possesses potent immunomodulatory and neuroprotective *** study investigated the effects of ASIV on post-ischemic brain infiltration and activation of NK *** reduced brain infarction and alleviated functional deficits in MCAO rats,and these beneficial effects persisted for at least 7 *** NK cells infiltrated into the ischemic hemisphere on day 1 after brain ischemia,and this infiltration was suppressed by ***,ASIV reversed NK cell deficiency in the spleen and blood after brain *** inhibited astrocyte-derived CCL2 upregulation and reduced CCR2+NK cell levels in the ischemic ***,ASIV attenuated NK cell activating receptor NKG2D levels and reduced interferon-γ*** restored acetylation of histone H3 and the p65 subunit of nuclear factor-κB in the ischemic brain,suggesting inhibition of histone deacetylase(HDAC).Simultaneously,ASIV prevented p65 nuclear *** effects of ASIV on reducing CCL2 production,restoring acetylated p65 levels and preventing p65 nuclear translocation were mimicked by valproate,an HDAC inhibitor,in astrocytes subjected to oxygen-glucose *** findings suggest that ASIV inhibits post-ischemic NK cell brain infiltration and activation and reverses NK cell deficiency in the periphery,which together contribute to the beneficial effects of ASIV against brain ***,ASIV’s effects on suppressing NK cell brain infiltration and activation may involve HDAC inhibition.

关键词： astragalosideⅣ brain ischemia natural killer cells histone deacetylase nuclear factor-κB

High specificity detection of Pb^2＋ ions by p-SCN-Bz-DTPA immunogen and p-NH2-Bn-DTPA coating antigen

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Frontiers of Environmental Science & Engineering 2014年第5期8卷 729-736页

作者： Ruozhen YU Zheng FANG Wei MENG Zhenguang YAN Lina DU Hong wang zhengtao LIU State Key Laboratory of Environmental Criteria and Risk Assessment Chinese Research Academy of Environmental Sciences Beijing 100012 China

Only one bifunctional metal-chelator was used to prepare immunogen and coating antigen in all of the previous researches. However, the antibody-specific recognition to the spacer arm of the bifunctional metal- chelator might lower the specificity of heavy metal ions immunoassay. Two different bifunctional metal-chelators were adopted to prepare the immunogen and coating antigen respectively in our study to avoid this problem. The conjugates of keyhole limpet hemocyanin （KLH） and p-SCN-Bz-DTPA-Pb were used as immunogen, whereas the conjugates of bovine sentrn albumin （BSA） and p- NH2-Bn-DTPA-Pb were used as coating antigen. Poly- clonal antibodies specific to DTPA-Pb chelates were obtained from rabbits. Indirect competitive enzyme-linked immunosorbent assay （ELISA） was adopted to detect Pb^2＋ ion solutions prepared by Pb^2＋ standard solution and ultrapure water. In the mixing microplate, DTPA and Pb2＋ ions formed chelates and combined with specific anti- bodies. After incubation, the DTPA-Pb and the antibodies complex were added into the wells of the reaction microplate. The reaction microplate was coated by the conjugates ofBSA andp-NH2-DTPA-Pb, which competed for the specific antibodies. The result signals presented a good sigmoid curve when the Pb^2＋ concentration ranges from 0.01 to 100mg·L^-1 The IC50 of the indirect competitive ELISA is 0.23±0.04mg·L^-1 Pb2＋ ion. The cross-reaction with Cd^2＋, Cu^2＋, Fe^2＋, Mn^2＋, Zn^2＋, and other divalent ions were less than 5%.

关键词： p-SCN-Bz-DTPA p-NH2-Bn-DTPA leadion polyclonal antibody

Chiral resolution of furofuran lignans and their derivatives from the stems of Dendrobium'Sonia'

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Chinese Journal of Natural Medicines 2024年第10期22卷 937-944页

作者： QIU Kaimei QIU Hao XIE Yanqiao ZHANG Siyu ZHANG Qian wang zhengtao HAN Zhuzhen YANG Li The MOE Key Laboratory of Standardization of Chinese Medicines The SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese MedicinesThe Shanghai Key Laboratory for Compound Chinese MedicinesInstitute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineShanghai 201203China

Five new furofuran lignans and their derivatives,(-)-glaberide I 4-O-β-D-glucopyranoside(1a),(+)-glaberide I 4-O-β-D-glucopyranoside(1b),(+)-glaberide I 7'-ethoxy-4-O-β-D-glucopyranoside(2a),(-)-glaberide I 7'-ethoxy-4-O-β-D-glucopyranoside(2b),and(-)-isoeucommin A(3b),along with fifteen known analogs were isolated from the stems of Dendrobium'Sonia'.These compounds were classified into ten pairs of enantiomers or diastereoisomers via chiral resolution,and their structures were determined based on extensive spectroscopic *** absolute configurations were determined by hydrolysis,comparison of experimental and calculated electronic circular dichroism(ECD)data,and single-crystal X-ray diffraction *** isolates were evaluated for their ability to inhibit nitric oxide(NO)production in RAW264.7 *** them,syringaresinol(5)exhibited prominent inhibition activity,with an IC50 value of 28.4±3.0μmol·L~(-1),and there was a slight difference between 5a,5b and the racemic mixture 5.

关键词： Furofuran lignans Chiral resolution Enantiomers Diastereoisomers Dendrobium'Sonia' Anti-inflammatory

Pyrrolizidine alkaloids:An update on their metabolism and hepatotoxicity mechanism

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Liver Research 2019年第3期3卷 176-184页

作者： Jie Xu Weiqian wang Xiao Yang Aizhen Xiong Li Yang zhengtao wang The Ministry of Education Key Laboratory for Standardization of Chinese Medicines and the State Administration of Traditional Chinese Medicine Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines Institute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineShanghaiChina Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese MedicinesShanghaiChina

Pyrrolizidine alkaloids(PAs)are among the most hepatotoxic natural compounds that are widely distributed throughout the *** PAs are metabolically activated to trigger *** to herbal medicine containing PAs and food supplements contaminated by PAs is considered to be one of the two main causes of hepatic sinusoidal obstruction syndrome(HSOS),which is a rare hepatic vascular disease with a high mortality ***-induced HSOS cases have been reported ***,there is no clinically effective therapy for PAs-induced HSOS,which is partially because the toxic mechanism is not fully *** review focuses on updating the information on the metabolism and the molecular mechanisms of PAs hepatotoxicity,including oxidative stress,apoptosis,and dysfunction of bile acid metabolism,and their interactions.

关键词： Pyrrolizidine alkaloids(PAs) Hepatic sinusoidal obstruction syndrome (HSOS) Metabolism Toxicity mechanism Oxidative stress Apoptosis Dysfunction of bile acid metabolism

Notoginsenoside Ft1 acts as a TGR5 agonist but FXR antagonist to alleviate high fat diet-induced obesity and insulin resistance in mice

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Acta Pharmaceutica Sinica B 2021年第6期11卷 1541-1554页

作者： Lili Ding Qiaoling Yang Eryun Zhang Yangmeng wang Siming Sun Yingbo Yang Tong Tian Zhengcai Ju Linshan Jiang Xunjiang wang zhengtao wang Wendong Huang Li Yang Shanghai Key Laboratory of Complex Prescriptions and MOE Key Laboratory for Standardization of Chinese Medicines Institute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineShanghai 201203China Department of Diabetes Complications and Metabolism Diabetes and Metabolism Research InstituteBeckman Research InstituteCity of Hope National Medical CenterDuarteCA 91010USA Department of Pharmacy Shanghai Children's HospitalShanghai Jiao Tong UniversityShanghai 200040China Graduate School of Biological Science City of Hope National Medical CenterDuarteCA 91010USA Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese MedicineShanghai 201203China Jiangsu Kanion Pharmaceutical Co. Ltd.Lianyungang 222001China

Obesity and its associated complications are highly related to a current public health crisis around the world.A growing body of evidence has indicated that G-protein coupled bile acid(BA) receptor TGR5(also known as Gpbar-1) is a potential drug target to treat obesity and associated metabolic *** have identified notoginsenoside Ftl(Ftl) from Panax notoginseng as an agonist of TGR5 in ***,the pharmacological effects of Ftl on diet-induced obese(DIO) mice and the underlying mechanisms are still *** we show that Ftl(100 mg/100 diet) increased adipose lipolysis,promoted fat browning in inguinal adipose tissue and induced glucagon-like peptide-1(GLP-1) secretion in the ileum of wild type but not Tgr5^(-/-) obese *** addition,Ftl elevated serum free and taurineconjugated bile acids(BAs) by antagonizing Fxr transcriptional activities in the ileum to activate Tgr5 in the adipose *** metabolic benefits of Ftl were abolished in Cyp27 al^(-/-) mice which have much lower BA *** results identify Ftl as a single compound with opposite activities on two key BA receptors to alleviate high fat diet-induced obesity and insulin resistance in mice.

关键词： Notoginsenoside Ft1 Obesity Insulin resistance Bile acids TGR5 FXR GLP-1 Metabolic disorders

Notoginsenoside Ft1 inhibits colorectal cancer growth by increasing CD8^(+)T cell proportion in tumor-bearing mice through the USP9X signaling pathway

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Chinese Journal of Natural Medicines 2024年第4期22卷 329-340页

作者： FENG Yutao LI Yuan MA Fen WU Enjiang CHENG Zewei ZHOU Shiling wang zhengtao YANG Li SUN Xun ZHANG Jiwei Shanghai Key Laboratory of Compound Chinese Medicines The MOE Key Laboratory for Standardization of Chinese MedicinesInstitute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineShanghai 201203China Gastrointestinal surgery Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China

The management of colorectal cancer(CRC)poses a significant challenge,necessitating the development of innovative and effective *** research has shown that notoginsenoside Ft1(Ng-Ft1),a small molecule,markedly inhibits subcutaneous tumor formation in CRC and enhances the proportion of CD8^(+)T cells in tumor-bearing mice,thus restraining tumor *** into the mechanism revealed that Ng-Ft1 selectively targets the deubiquitination enzyme USP9X,undermining its role in shieldingβ-*** leads to a reduction in the expression of downstream effectors in the Wnt signaling *** findings indicate that Ng-Ft1 could be a promising small-molecule treatment for CRC,working by blocking tumor progression via the Wnt signaling pathway and augmenting CD8^(+)T cell prevalence within the tumor environment.

关键词： Notoginsenoside Ft1 Colorectal cancer CD8^(+)T cell Ubiquitin-specific peptidase 9 X-linked β-Catenin Wnt

Targeted bile acids metabolomics in cholesterol gallbladder polyps and gallstones: From analytical method development towards application to clinical samples

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Journal of Pharmaceutical Analysis 2023年第9期13卷 1080-1087页

作者： Jiaojiao Wei Tao Chen Yamin Liu Shuai Sun Zhiqing Yuan Yixin Zhang Aizhen Xiong Linnan Li zhengtao wang Li Yang The MOE Key Laboratory of Standardization of Chinese Medicines The SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese MedicinesThe Shanghai Key Laboratory for Compound Chinese MedicinesInstitute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineShanghai 201203China Department of Biliary and Pancreatic Surgery Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200127China

Bile acids(BAs)are synthesized by the liver from cholesterol through several complementary pathways and aberrant cholesterol metabolism plays pivotal roles in the pathogeneses of cholesterol gallbladder polyps(CGP)and cholesterol gallstones(CGS).To date,there is neither systematic study on BAs profile of CGP or CGS,nor the relationship between *** explore the metabolomics profile of plasma BAs in healthy volunteers,CGP and CGS patients,an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method was developed and validated for simultaneous determination of 42 free and conjugated BAs in human *** developed method was sensitive and reproducible to be applied for the quantification of BAs in the investigation of plasma *** results show that,compared to healthy volunteers,CGP and CGS were both characterized by the significant decrease in plasma BAs pool size,furthermore CGP and CGS shared aberrant BAs metabolic *** acid,glycochenodeoxycholic acid,l-muricholic acid,deoxycholic acid,and 7-ketolithocholic acid were shared potential markers of these two cholesterol gallbladder *** analysis showed that clinical characteristics including cysteine,ornithine and body mass index might be closely related to metabolisms of certain BA *** work provides metabolomic information for the study of gallbladder diseases and analytical methodologies for clinical target analysis and efficacy evaluation related to BAs in medical institutions.

关键词： Bile acid metabolism Gallbladder polyps Gallstones Metabolomics UPLC-MS/MS