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Toxicity comparison of different active fractions extracted from radix Sophorae tonkinensis in zebrafish

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Journal of Zhejiang University-Science B(Biomedicine & biotechnology) 2017年第9期18卷 757-769页

作者： Hong-cui LIU Xiao-yu ZHU Jiang-hua CHEN Sheng-ya GUO Chun-qi LI Zhong-ping DENG Center for Drug Safety Evaluation and Research Shanghai University of Traditional Chinese Medicine hunter biotechnology Inc.

Radix Sophorae tonkinensis(RST) is a widely used herb in Traditional Chinese Medicine(TCM) for treating infectious and inflammatory diseases. However, the toxicity data for RST are limited. The aim of this work is to assess and compare the toxicity of the whole RST extract and its five active fractions using the zebrafish model. Five active fractions of RST were prepared using five different types of solvents, which included dealkalized water, ethanol, n-butyl ethanol, dichloromethane, and diethyl ether. The chemical profiles of the active fractions were determined by high-performance liquid chromatography(HPLC), and the toxicity observed in the zebrafish model was confirmed using mouse models. In the zebrafish model, cardiovascular toxicity was observed for the fraction extracted using diethyl ether, and hepatotoxicity was observed for the whole RST extract and the fractions extracted using water and ethanol, whereas both cardiovascular and hepatic toxicities were observed for the fractions extracted using n-butyl ethanol and dichloromethane. The hepatotoxicity of the fractions extracted using n-butyl ethanol and dichloromethane was also observed in mice. Our findings provide the toxicity data for RST and its five active fractions through modeling in a zebrafish, and indicate that the different fractions may each have a different toxicity, which is helpful for the optimal use of RST in clinical practice.

关键词： Sophorae tonkinensis Gagnep Active fraction Hepatotoxicity Cardiovascular toxicity Zebrafish

Modified Sijunzi Granules Exhibit Hemostatic Effect by Activating Akt and Erk Signal Pathways via Regulating 5-HT and Its Receptors Levels

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Chinese Journal of Integrative Medicine 2024年第12期30卷 1121-1127页

作者： WANG Jun ZHANG Xue-ying KANG Yan-hong ZHANG Yun CHEN Xin-yi ZHOU Jia-li MA Wei Department of Hematology the First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou 310006China Department of Hemato-Oncology Dongzhimen HospitalBeijing University of Chinese MedicineBeijing 100700China hunter biotechnology Inc.Hangzhou 310051China

Objective:To investigate the hemostatic effect of modified Sijunzi Granules(MSG)in primary immune thrombocytopenia(ITP)zebrafish model and explore the potential ***:AB strain wild type zebrafish were treated with simvastatin(6μmol/L)for 24 h to establish the hemorrhage model(model control group).The zebrafish were treated with MSG at different doses(55.6,167,and 500μg/mL),*** hemostatic effect was assessed by examining the intestinal bleeding and hemostatic rate.5-hydroxytryptamine(5-HT)content was determined using enzyme-linked immunosorbent assay(ELISA)*** expressions of5-HT2aR,5-HT2bR,and SERT genes were detected by quantitative real-time polymerase chain reaction(PCR).The protein expressions of protein kinase B(Akt),p-Akt,extracellular regulated protein kinases(Erk),and p-Erk were examined using Western blot ***:The intestinal bleeding rate was 37%,40%,and 80%in the55.6,167,and 500μg/mL dose of MSG,respectively,in which 55.6 and 167μg/mL MSG dose groups were associated with significantly decreased intestinal bleeding rate when compared with the model control group(70%,P<0.05).Significantly higher hemostatic rates were also observed in the 55.6μg/mL(54%)and 167μg/mL(52%)MSG dose groups(P<0.05).MSG increased the 5-HT content and mRNA expression levels of 5-HT2aR,5-HT2bR,and SERT(P<0.05).In addition,caspase3/7 activity was inhibited(P<0.05).Significant increase in p-Akt and p-Erk was also detected after treatment with MSG(P<0.05).Conclusions:MSG could reduce the incidence and severity of intestinal bleeding in zebrafish by activating MAPK/Erk and PI3K/Akt signal pathways through regulating the levels of 5-HT and its receptors,which may provide evidence for the treatment of ITP.

关键词： modified Sijunzi Granules Chinese medicine primary immune thrombocytopenia zebrafish 5-hydroxytryptamine 5-hydroxytryptamine receptor mitogen-activated protein kinase/extracellular regulated protein kinases signal pathway phosphoinositide3-kinases/protein kinase B signal pathway

Zebrafish-based natural product drug discovery

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Zebrafish-based natural product drug discovery

Development of a Zebrafish Model for Rapid Drug Screening against Alzheimer＇s Disease

第一届《药学学报》药学前沿论坛暨2015年中国药学会中药与天然药物专业委员会会议

作者： LI Chun-qi XU Yi-qiao LIU Hong-cui ZHU Xiao-yu LAN Xiao-hong LAO Qiao-cong ZHANG Yong hunter biotechnology Corp. Institute of Watershed Science and Environmental Ecology Wenzhou Medical University

Zebrafish as a vertebrate animal model is increasingly used for in vivo drug discovery and for assessing drug toxicity and *** studies confirm that mammalian and zebrafish physiology,development,metabolism and pathways are strikingly similar and zebrafish is extremely predictive of mammalian *** convenient and predictive animal model offers several compelling experimental advantages including transparency,high throughput,short test period,low cost,small amount of compound required,easy manipulation and direct compound delivery,et *** and EMEA have accepted zebrafish toxicity and safety assessment data for IND approval and more than one dozen of new drugs including natural products discovered primarily based on zebrafish model are now in clinical *** this reivew,we will introduce:① the background of zebrafish-based natural product drug discovery;② zebrafish models for assessing natural product toxicity and safety including acute toxicity,LC,development toxiciy & teratogenicity,cardiovascular toxicity,liver toxicity,nerve toxicity,behavior toxicity,blood toxicity,anaphylactoid reaction and so on;③ zebrafish models of human diseases for natural product drug discovery including anti- and pro-angiogenesis models,cancer models,cardiovascular disease models,CNS disease models,liver and metabolic disease models,inflammatory and bone disease models,and so on;④zebrafish models and assays for traditional Chinese medicine(TCM),TCM biologically quality control,TCM processing optimization and native Chinese herb *** drug discovery platform can reduce the time and cost required for the natural product drug development process.

关键词： zebrafish natural product toxicity drug discovery

来源： cnki会议评论

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cnki会议

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Journal of Pharmacy and Pharmacology 2016年第4期4卷 162-173页

作者： Wenhai Huang Chuansheng Li Zhengrong Shen Xiaoyu Zhu Bo Xia Chunqi Li Institute of Materia Medica Zhejiang Academy of Medical Sciences Hangzhou 310013 Zhejiang Province China hunter biotechnology Inc. Transfarland Hangzhou 310013 Zhejiang Province China

Alzheimer＇s disease, the leading cause of dementia in the elderly, is a complex neurodegenerative disorder which leads to a progressive decline in cognitive functions. A rapid screening model is highly demanded for identification and evaluation of novel anti-Alzheimer＇s disease drugs from a large numbers of compounds. Until now, numerous studies utilized zebrafish model for drug discovery. Since aluminum can induce a similar biological activity in zebrafish as in Alzheimer patients, in this study, we developed a novel animal model using 3 to 5 day post-fertilization larval zebrafish by optimizing the doses and duration of aluminum chloride exposure. Six anti-Alzheimer＇s disease drugs with a variety of mechanisms were tested to validate the newly developed zebrafish model. Importantly, Rivastigmine, ThT, Flurbiprofen and AM-117 could increase the value of Dyskinesia Recovery Rate by 53.4-64%, 169.4-200%, 54.5-96% and 70.9-121%, respectively. Rivastigmine, Memantine, ThT, Flurbiprofen, Rosiglitazone and AM-117 improved the value of Response Efficiency by 86.6-175.1%, 28.2-66.6%, 127.2-236.5%, 118.3-323.7%, 26.6-140.8% and 70.2-161.4%, respectively. Our results suggest that the zebrafish model developed in this study could be a useful tool for high throughput screening of potential novel anti-Alzheimer＇s disease leading compounds targeting acetylcholinesterase, N-methyl-D-aspartic acid receptor, γ-secretase, peroxisome proliferator-activated receptor-γand amyloid-β.

关键词： Alzheimer's disease 3-5dpf Larvae screening platform zebrafish model.

PHLPP phosphatase:a key mediator integrating multiple signaling pathways

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维普期刊数据库

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Frontiers in Biology 2010年第3期5卷 193-194页

作者： Hui ZHONG State key Laboratory of Pathogen and Biosecurity Beijing Institute of BiotechnologyBeijing 100850China

Cellular responses to bacterial or viral infections and to stress require rapid and accurate transmission of signals from cell-surface receptors to the nucleus(Karin and hunter,1995).These signaling pathways,relying on extensive protein phosphorylation events,lead to the activation of specific transcription factors that induce the expression of appropriate target *** the activated transcription factors,nuclear factor kB(NF-kB)is essential for inflammation,immunity,cell proliferation and ***-kB requires a signaling pathway for *** NF-kB-activating pathways can be triggered by a variety of extracellular stimuli,which lead to the phosphorylation and subsequent proteasomemediated degradation of inhibitory molecules,the inhibitor of NF-kB(IkB)proteins(Karin and Ben-Neriah,2000).Activated NF-kB migrates into the nucleus to regulate the expression of multiple target genes.

关键词： immunity inflammation integrating

Insights into Triclosan-Induced Endocrine Disruption:Evidence from the National Health and Nutrition Examination Survey and Zebrafish Models

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Environment & Health 2024年第7期2卷 424-440页

作者： Zhiming Li Hongyi Xian Xiaohu Ren Rongyi Ye Yizhou Zhong Yuji Huang Boxuan Liang Yanhong Deng Mingzhu Dai Jie Guo Shuqin Tang Jialiang Pan Yu Feng Ruobing Bai Xueping Chen Sahoko Ichihara Gaku Ichihara Da Chen Xingfen Yang Zhenlie Huang NMPA Key Laboratory for Safety Evaluation of Cosmetics Guangdong Provincial Key Laboratory of Tropical Disease ResearchDepartment of ToxicologySchool of Public HealthSouthern Medical UniversityGuangzhou 510515China Shenzhen Key Laboratory of Modern Toxicology Shenzhen Medical Key Discipline of Health ToxicologyShenzhen Center for Disease Control and PreventionShenzhen 518055China hunter biotechnology Inc.Hangzhou 310051China College of Environment and Climate Guangdong Provincial Key Laboratory of Environmental Pollution and HealthJinan UniversityGuangzhou 510632China Vitargent(International)biotechnology Limited Shatin 999077Hong Kong SARChina Department of Environmental and Preventive Medicine School of MedicineJichi Medical UniversityTochigi 329-0498Japan Department of Occupational and Environmental Health Faculty of Pharmaceutical SciencesTokyo University of ScienceNoda 278-8510Japan

Triclosan(TCS)has garnered significant attention due to its widespread use and associated endocrine-disrupting ***,its impact on the neuroendocrine system and underlying mechanisms remain poorly ***,we established correlations between TCS exposure and serum sex hormone levels in participants of the National Health and Nutrition Examination Survey(NHANES).Additionally,we investigated TCS’s influence on the neuroendocrine system using adult zebrafish exposed to environmentally relevant concentrations of TCS(0.361–48.2μg/L)for 21 *** of reproductive and neurotoxicity included histopathological examination and behavioral ***,proteomics analyses,and biochemical detection were employed to elucidate mechanisms underlying TCS-induced neuroendocrine *** correlations were found between TCS exposure and estradiol,testosterone,and sex hormone-binding globulin levels in NHANES *** addition,TCS exposure inhibited ovary development and spermatogenesis in *** and proteomics analysis revealed gender-specific key signaling and metabolism-related pathways implicated in TCS-induced reproductive ***,TCS exposure induced nervous system impairment,as evidenced by histological changes and altered motor behavior,possibly associated with oxidative *** analysis further highlighted the potential connection between endocrine system disruption and nervous system impairment following TCS ***,this study provided evidence supporting TCS-induced endocrine disruption and offered insights into its underlying mechanisms.

关键词： Emerging Contaminants Ecotoxicity Public Health Endocrine-Disrupting Chemicals Endocrine-Disrupting Effects

Histo-blood group antigens in Crassostrea gigas and binding profiles with GⅡ.4 Norovirus

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维普期刊数据库

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Journal of Oceanology and Limnology 2018年第4期36卷 1383-1391页

作者： MA Liping LIU Hui SU Laij in ZHAO Feng ZHOU Deqing DUAN Delin Key Laboratory of Experimental Marine Biology Institute of OceanologyChinese Academy of SciencesQingdao 266071China Key Laboratory for Sustainable Utilization of Marine Fisheries Resources Ministry of AgricultureYellow Sea Fisheries Research InstituteChinese Academy of Fishery SciencesQingdao 266071China Laboratory for Marine Biology and biotechnology Qingdao National Laboratory for Marine Science and TechnologyQingdao 266071China

Noroviruses(NoVs) are the main cause of viral gastroenteritis outbreaks worldwide, and oysters are the most common carriers of NoV contamination and transmission. NoVs bind specifically to oyster tissues through histo-blood group antigens(HBGAs), and this facilitates virus accumulation and increases virus persistence in oysters. To investigate the interaction of HBGAs in Pacific oysters with GⅡ.4 NoV, we examined HBGAs with ELISAs and investigated binding patterns with oligosaccharide-binding assays using P particles as a model of five GⅡ.4 NoV capsids. The HBGAs in the gut and gills exhibited polymorphisms. In the gut, type A was detected(100%), whereas type Leb(91.67%) and type A(61.11%) were both observed in the gills. Moreover, we found that seasonal NoV gastroenteritis outbreaks were not significantly associated with the specific HBGAs detected in the oyster gut and gills. In the gut, we found that strain-2006 b and strain-96/96 US bound to type A and H1 but only weakly bound to type Leb; in contrast, the Camberwell and hunter strains exhibited weak binding to types H1 and Ley, and strain-Sakai exhibited no binding to any HBGA type. In the gills, strain-96/96 US and strain-2006 b bound to type Leb but only weakly bound to type H1; strains Camberwell, hunter, and Sakai did not bind to oyster HBGAs. Assays for oligosaccharide binding to GⅡ.4 NoV P particles showed that strain-95/96 US and strain-2006 b strongly bound to type A, B, H1, Leb, and Ley oligosaccharides, while strains Camberwell and hunter showed weak binding ability to type H1 and Ley oligosaccharides and strain-Sakai showed weak binding ability to type Leb and Ley oligosaccharides. Our study presents new information and enhances understanding about the mechanism for NoV accumulation in oysters. Further studies of multiple NoV-tissue interactions might assist in identifying new or improved strategies for minimizing contamination, including HBGA-based attachment inhibition or depuration.

关键词： Crassostrea gigas norovirus histo-blood group antigen binding

Small interfering RNA for cancer treatment:overcoming hurdles in delivery

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Acta Pharmaceutica Sinica B 2020年第11期10卷 2075-2109页

作者： Nitin Bharat Charbe Nikhil D.Amnerkar B.Ramesh Murtaza M.Tambuwala Hamid A.Bakshi Alaa A.A.Aljabali Saurabh C.Khadse Rajendran Satheeshkumar Saurabh Satija Meenu Metha Dinesh Kumar Chellappan Garima Shrivastava Gaurav Gupta Poonam Negi Kamal Dua Flavia C.Zacconin Departamento de Quimica Orgánica Facultad de Química y de FarmaciaPontificia Universidad Católica de ChileSantiago 7820436Chile Sri Adichunchunagiri College of Pharmacy Sri Adichunchunagiri UniversityBG NagarKarnataka 571418India Adv V.R.Manohar Institute of Diploma in Pharmacy NagpurMaharashtra 441110India School of Pharmacy and Pharmaceutical Science Ulster UniversityColeraineNorthern Ireland BT521SAUK Faculty of Pharmacy Department of Pharmaceutics and Pharmaceutical TechnologyYarmouk UniversityIrbid 21163Jordan Department of Pharmaceutical Chemistry R.C.Patel Institute of Pharmaceutical Education and ResearchDist.DhuleMaharashtra 425405India Discipline of Pharmacy Graduate School of HealthUniversity of Technology SydneyNSW 2007Australia School of Pharmaceutical Sciences Lovely Professional UniversityPhagwara 144411 PunjabIndia Department of Life Sciences School of PharmacyInternational Medical UniversityBukit Jalil 57000Kuala LumpurMalaysia Department of Biochemical Engineering and biotechnology Indian Institute of TechnologyDelhiNew Delhi 110016India School of Pharmacy Suresh Gyan Vihar UniversityJagatpuraJaipur 302017India School of Pharmaceutical Sciences Shoolini University of Biotechnology and Management SciencesSolan 173229India Priority Research Centre for Healthy Lungs Hunter Medical Research Institute(HMRI)and School of Biomedical Sciences and PharmacyUniversity of NewcastleNSW 2308Australia Institute for Biological and Medical Engineering Schools of EngineeringMedicine and Biological SciencesPontificia Universidad Católica de ChileSantiago 4860Chile

In many ways,cancer cells are different from healthy cells.A lot of tactical nano-based drug delivery systems are based on the difference between cancer and healthy ***,nanotechnology-based delivery systems are the most promising tool to deliver DNA-based products to cancer *** review aims to highlight the latest development in the lipids and polymeric nanocarrier for siRNA delivery to the cancer *** also provides the necessary information about siRNA development and its mechanism of ***,this review gives us a clear picture of lipid and polymer-based drug delivery systems,which in the future could form the base to translate the basic siRNA biology into siRNA-based cancer therapies.

关键词： Small interfering RNA(siRNA) Nanomedicine Liposomes Micelles Cancer Polymer

Revealing CO_(2)-Fixing SAR11 Bacteria in the Ocean by Raman-Based Single-Cell Metabolic Profiling and Genomics

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BioDesign Research 2022年第1期2022卷 52-67页

作者： Xiaoyan Jing Yanhai Gong Teng Xu Paul ADavison Craig MacGregor-Chatwin CNeil hunter La Xu Yu Meng Yuetong Ji Bo Ma Jian Xu Wei E.Huang Single-Cell Center CAS Key Laboratory of BiofuelsShandong Key Laboratory of Energy Genetics and Shandong Institute of Energy ResearchQingdao Institute of Bioenergy and Bioprocess TechnologyChinese Academy of SciencesQingdaoShandongChina Laboratory for Marine Biology and biotechnology Qingdao National Laboratory for Marine Science and TechnologyQingdaoShandongChina University of Chinese Academy of Sciences BeijingChina Plants Photosynthesis and SoilSchool of BiosciencesUniversity of SheffieldSheffield S102TNUK Disease and Fishery Drugs Research Center Marine Biology Institute of Shandong ProvinceQingdaoShandongChina Single-Cell biotechnology LtdQingdaoShandongChina Department of Engineering Science University of OxfordParks RoadOX13PJ OxfordUK

The majority of marine microbes remain uncultured,which hinders the identification and mining of CO_(2)-fixing genes,pathways,and chassis from the ***,we investigated CO_(2)-fixing microbes in seawater from the euphotic zone of the Yellow Sea of China by detecting and tracking their ^(13)C-bicarbonate(^(13)C-HCO_(3)^(-))intake via single-cell Raman spectra(SCRS)*** target cells were then isolated by Raman-activated Gravity-driven Encapsulation(RAGE),and their genomes were amplified and sequenced at one-cell *** single-cell metabolism,phenotype and genome are *** identified a notyet-cultured Pelagibacter spp.,which actively assimilates ^(13)C-HCO_(3)^(-),and also possesses most of the genes encoding enzymes of the Calvin-Benson cycle for CO_(2) fixation,a complete gene set for a rhodopsin-based light-harvesting system,and the full genes necessary for carotenoid *** four proteorhodopsin(PR)genes identified in the Pelagibacter *** confirmed by heterologous expression in *** results suggest that hitherto uncultured Pelagibacter *** light-powered metabolism to contribute to global carbon cycling.

关键词： metabolism Benson hinder