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The interaction between polyphyllin I and SQLE protein induces hepatotoxicity through SREBP-2/HMGCR/SQLE/LSS pathway

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Journal of Pharmaceutical Analysis 2023年第1期13卷 39-54页

作者： Zhiqi Li Qiqi Fan Meilin Chen Ying Dong Farong Li Mingshuang Wang Yulin Gu Simin Guo Xianwen Ye Jiarui Wu Shengyun Dai ruichao lin Chongjun Zhao Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica School of Chinese Materia MedicaBeijing University of Chinese MedicineBeijing100029China Key Laboratory of Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of ChinaShaanxi Normal UniversityXi'an710119China National Institutes for Food and Drug Control Beijing102629China

Polyphyllin I(PPI)and polyphyllin II(PII)are the main active substances in the Paris ***,liver toxicity of these compounds has impeded their clinical application and the potential hepatotoxicity mechanisms remain to be *** this work,we found that PPI and PII exposure could induce significant hepatotoxicity in human liver cell line L-02 and zebrafish in a dose-dependent *** results of the proteomic analysis in L-02 cells and transcriptome in zebrafish indicated that the hepatotoxicity of PPI and PII was associated with the cholesterol biosynthetic pathway disorders,which were alleviated by the cholesterol biosynthesis inhibitor ***,3-hydroxy-3-methy-lglutaryl CoA reductase(HMGCR)and squalene epoxidase(SQLE),the two rate-limiting enzymes in the cholesterol synthesis,selected as the potential targets,were confirmed by the molecular docking,the overexpression,and knockdown of HMGCR or SQLE with ***,the pull-down and surface plasmon resonance technology revealed that PPI could directly bind with SQLE but not with ***,these data demonstrated that PPI-induced hepatotoxicity resulted from the direct binding with SQLE protein and impaired the sterol-regulatory element binding protein 2/HMGCR/SQLE/lanosterol synthase pathways,thus disturbing the cholesterol biosynthesis *** findings of this research can contribute to a better understanding of the key role of SQLE as a potential target in drug-induced hepatotoxicity and provide a therapeutic strategy for the prevention of drug toxic effects with similar structures in the future.

关键词： Polyphyllin I Polyphyllin II Zebrafish Hepatotoxicity SQLE

经典名方五子衍宗丸干预半去势雄性小鼠生精功能的转录组学分析

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中国实验方剂学杂志 2024年第1期30卷 61-69页

作者：邹迪新张岳阳孟雪丹鹿伟吕爽曾凡俊陈坤刘畅张钟秀段宇代一航王昭懿王智民林瑞超中国中医科学院中药研究所北京100700 中国中医科学院望京医院北京100102 北京中医药大学中药学院中药品质评价中心/北京市重点实验室北京100102 内蒙古医科大学附属医院呼和浩特010050 河北医科大学第一医院石家庄050031 海关总署(北京)国际旅行卫生保健中心北京100013 北京市药品检验研究院北京市疫苗检验中心北京102206 北京体育大学运动人体科学学院北京100084

目的:筛选五子衍宗丸干预半去势雄性小鼠生精功能相关的转录组,探讨其在干预生精功能低下进展中的潜在作用机制。方法:Balb/c小鼠按体质量随机分为假手术组、模型组、丙酸睾丸素组、五子衍宗丸组,每组12只,模型组和给药组摘取右侧睾丸... 详细信息

目的:筛选五子衍宗丸干预半去势雄性小鼠生精功能相关的转录组,探讨其在干预生精功能低下进展中的潜在作用机制。方法:Balb/c小鼠按体质量随机分为假手术组、模型组、丙酸睾丸素组、五子衍宗丸组,每组12只,模型组和给药组摘取右侧睾丸和附睾构建半去势生精功能低下模型,假手术组仅剪开毛皮和右侧阴囊并立即消毒缝合,饲养1周后,五子衍宗丸组每天灌胃五子衍宗丸混悬液1.56 g·kg^(-1),丙酸睾丸素组肌肉注射丙酸睾丸素0.2 mg·kg^(-1),每周2次,假手术组和模型组每天灌胃等体积生理盐水,连续给药3周。干预结束后,苏木素-伊红(HE)染色观察睾丸组织病理;酶联免疫吸附测定法(ELISA)检测血清睾酮(T)、促黄体生成素(LH)和卵泡刺激素(FSH)含量;小动物精子自动检测仪测定附睾精子数量和活力;利用转录组学芯片技术检测各组睾丸组织mRNA表达水平,筛选五子衍宗丸调控相关基因转录组,并从中任选3条mRNA进行实时荧光定量聚合酶链式反应(Real-time PCR)验证转录组数据。验证合格的转录组数据通过基因本体(GO)注释分析及京都基因和基因组百科全书(KEGG)信号通路富集分析,解析五子衍宗丸调控模型动物生精功能相关的生物条目及信号通路。结果:与假手术组比较,模型组小鼠睾丸组织出现生精损伤,生精小管腔收缩、空泡化、各级生精细胞减少、间隙变宽,生精细胞发育阻滞等形态异常;血清T显著降低,LH显著升高(P<0.01),FSH升高但差异无统计学意义;附睾精子数量、活力均显著降低(P<0.01);睾丸组织中有882条差异表达mRNA,其中565条上调,317条下调,聚类分析表明,这些差异表达的mRNA可以很好地区分假手术组与模型组。与模型组比较,五子衍宗丸组小鼠睾丸组织损伤减轻,生精小管腔结构完整、空泡化减少、各级生精细胞明显增加、排列紧密;血清中T显著升高,LH显著下降(P<0.01),FSH下降但差异无统计学意义;附睾中精子数量和活力显著提高(P<0.01);五子衍宗丸可明显调控半去势小鼠睾丸的159条mRNA,其中32条上调,127条下调,经Real-time PCR验证转录组检测数据可靠。GO和KEGG分析显示,五子衍宗丸调控的转录组功能涉及到睾丸内间质细胞的性激素生成,生精细胞的更新、分化、代谢、凋亡、信号传导等精子发育的整个细胞周期过程,并和生精干细胞功能、内质网蛋白处理及代谢程序等信号通路的生物学行为密切相关。结论:五子衍宗丸可有效改善半去势雄性小鼠造成的生精功能低下,其机制可能与五子衍宗丸干预睾丸转录调节网络,调控睾丸间质细胞性激素合成、生精干细胞功能、精子发生的整个细胞周期过程,以及内质网蛋白处理及代谢程序相关基因转录的表达有关。

关键词：经典名方五子衍宗丸半去势生精功能转录组学男性不育实时荧光定量聚合酶链式反应(Real-time PCR)

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加压薄层色谱法的原理及其应用

色谱 2006年第1期24卷 99-102页

作者：何轶鲁静林瑞超中国药品生物制品检定所北京100050

对加压薄层色谱的原理和应用作以介绍。介绍了加压薄层色谱的仪器结构、工作方式;对影响加压薄层色谱的因素、常见问题及解决方法进行了总结;简要地介绍了该方法在分析中的应用情况。

关键词：加压薄层色谱原理应用

Assay for the developmental toxicity of safflower (Carthamus tinctorius L.) to zebrafish embryos/larvae

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Journal of Traditional Chinese Medical Sciences 2017年第1期4卷 71-81页

作者： Qing Xia Zhiqiang Ma Xue Mei Jun Luo Yutong Wang Tongtong Li Yaru Feng Yuanyuan Ni Qinwen Zou ruichao lin Beijing Key Lab for Quality Evaluation of Chinese Materia Medica School of Chinese PharmacyBeijing University of Chinese MedicineBeijing100102China Department of Quality Control Beijing Lianxin Pharmaceutic Co.Ltd.Beijing102609China

Objective:To explore the developmental toxicity and the potential toxicological mechanism of safflower (Carthamus tinctorius L.) on zebrafish embryos/***:Mortality,malformations and increased apoptosis induced by safflower were assessed in zebraflsh embryos from 6 to 96 hours *** and genes in the anti-oxidative and apoptotic pathways were also ***:The lethal concentration 50 of safflower to zebrafish embryos was 345.6 mg/*** inhibition,abnormal spontaneous movement,depressed heart rate,pericardial edema,yolk sac edema,abnormal head-trunk angle,inhibition of melanin release,enlarged yolk,and short body length were observed in safflower-treated *** apoptotic cells mainly appeared around the *** exposure changed the activities of defense enzymes (SOD T,CAT↑,MDA↑,GPX without trend),increased MDA content,decreased caspase-3 activity,and altered mRNA levels of related genes (ogg1 ↓,p53↓,Cu/Zn-sod↑,Mn-sod↓,cat↓,gpx↑).Conclusion:Safflower exhibits developmental toxicity for zebrafish embryos/*** developing heart was speculated as the target organ of *** stress and increased apoptosis have roles in the developmental toxicity of *** article provides a novel method to research the teratogenicity and possible mechanisms of toxicity of traditional Chinese medicines that are prohibited or contraindicated in pregnant women.

关键词： Carthamus tinctorius L. Developmental toxicity Zebrafish Apoptosis Oxidative stress

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天山堇菜化学成分研究

中国中药杂志 2009年第22期34卷 2916-2917页

作者：于健东戴忠林瑞超中国药品生物制品检定所北京100050

目的:研究堇菜属Viola植物天山堇菜Viola tianshanica的化学成分。方法:采用硅胶、葡聚糖凝胶、聚酰胺柱色谱等技术分离纯化化合物,并根据理化常数、UV,IR,ESI-MS,1H-NMR和13C-NMR等鉴定其结构。结果:从天山堇菜正丁醇部分分离得到6个... 详细信息

目的:研究堇菜属Viola植物天山堇菜Viola tianshanica的化学成分。方法:采用硅胶、葡聚糖凝胶、聚酰胺柱色谱等技术分离纯化化合物,并根据理化常数、UV,IR,ESI-MS,1H-NMR和13C-NMR等鉴定其结构。结果:从天山堇菜正丁醇部分分离得到6个化合物,分别鉴定为:胡萝卜苷(1)、山柰酚-7-O-β-D-葡萄糖苷(2)、山柰酚-3-O-β-D-葡萄糖苷(3)、异鼠李素-3-O-葡萄糖苷(4)、山柰酚(5)、槲皮素(6)。结论:除胡萝卜苷外,皆为首次从该植物中分离得到。

关键词：天山堇菜化学成分黄酮

Using the Doubly Charged Selected Ion Monitoring (DC-SIM) Mode for the Identification of Gelatins Species

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Using the Doubly Charged Selected Ion Monitoring (DC-SIM) Mo...

第十五届中国科协年会第21分会场：中药与天然药物现代研究学术研讨会

作者： CHENG Xianlong LI Wenjie ZHANG Xiaolong WEI Feng XIAO Xinyue ZHANG Li lin ruichao MA Shuangcheng National Institutes for Food and Drug Control Beijing University of Chinese Medicine Lianyungang Institute for Drug Control

Gelatin is a mixture of high molecular weight polypeptides from the hydrolysis of collagen. Doubly Charged Selected Ion Monitoring (DC-SIM) is the most suitable scanning mode to detect known peptides in complex samples when an ion-trap mass spectrometer is the instrument used for the analysis. In this mode, the MS detector is programmed to perform continuous MS/MS on one or more selected precursors, either during a selected time interval, or along the whole chromatographic run. MS/MS spectra are recorded, so virtual multiple reaction monitoring chromatogram traces for the different fragment ions can be plotted. In this work, a PCA method was applied to the detection of previously characterized species-specific peptides from different gelatins. The proposed methodology makes use of trypsin digestion for sample preparation, peptide separation and identification by rapid resolution liquid chromatography coupled to an ion-trap working in the auto MS 2 mode. This methodology was applied to the differential classification of five commercial, homological,species of gelatins proving to be an excellent tool for gelatins product authentication, which may be used by manufacturers to provide a fast and effective identification of the gelatins, guaranteeing the quality and safety of foodstuffs to consumers.

关键词： Selected ion tandem mass spectrometry gelatin polypeptides and identification

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红外和近红外光谱法在中药定性分析中的应用

计算机与应用化学 2011年第5期28卷 540-544页

作者：聂黎行鲁静林瑞超中国食品药品检定研究院北京100050

目的:为中药的光谱研究提供参考。方法:综述了近年来红外和近红外光谱法在中药定性分析领域的应用,并对2种光谱技术的特点进行了比较。结果与结论:红外和近红外光谱法具有全面、快速、客观、无损等优点,为中药质量控制提供了新的思路。

关键词：中药定性分析红外近红外

9种人参皂苷同时测定方法及在人参质量鉴别中的应用

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分析化学 2005年第11期33卷 1565-1568页

作者：潘坚扬程翼宇王毅肖新月林瑞超浙江大学中药科学与工程学系中国药品生物制品检定所

建立可同时测定人参皂苷Rg1、Re、R f、Rg2、Rb1、R c、Rb2、Rb3和Rd含量的反相高效液相色谱(RP-HPLC)方法。采用Agilent Zorbax SB-C18柱,以乙腈-水-0.05%磷酸为流动相,流速1.5 mL/m in,柱温35℃,检测波长203 nm。在此色谱条件下,各组... 详细信息

建立可同时测定人参皂苷Rg1、Re、R f、Rg2、Rb1、R c、Rb2、Rb3和Rd含量的反相高效液相色谱(RP-HPLC)方法。采用Agilent Zorbax SB-C18柱,以乙腈-水-0.05%磷酸为流动相,流速1.5 mL/m in,柱温35℃,检测波长203 nm。在此色谱条件下,各组分在60 m in内均得到较好分离,回收率符合含量测定要求。运用该方法对不同产地人参进行含量测定,道地药材主根中9种人参皂苷总含量为1.19~1.45%,须根为5.47~6.90%,3个非道地药材主根分别为1.03%、1.04%、1.85%。聚类分析结果表明,根据测定的9种皂苷含量能准确区分人参的主根与须根,并判断其道地性。

关键词：人参皂苷反相高效液相色谱法含量测定聚类分析

A fast forward computational method for nuclear measurement using volumetric detection constraints

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Nuclear Science and Techniques 2024年第2期35卷 47-63页

作者： Qiong Zhang lin-Lv lin University of Electronic Science and Technology of China Chengdu 610000China

Owing to the complex lithology of unconventional reservoirs,field interpreters usually need to provide a basis for interpretation using logging simulation *** the various detection tools that use nuclear sources,the detector response can reflect various types of information of the *** Monte Carlo method is one of the primary methods used to obtain nuclear detection responses in complex ***,this requires a computational process with extensive random sampling,consumes considerable resources,and does not provide real-time response ***,a novel fast forward computational method(FFCM)for nuclear measurement that uses volumetric detection constraints to rapidly calculate the detector response in various complex environments is ***,the data library required for the FFCM is built by collecting the detection volume,detector counts,and flux sensitivity functions through a Monte Carlo ***,based on perturbation theory and the Rytov approximation,a model for the detector response is derived using the flux sensitivity function method and a one-group diffusion *** environmental perturbation is constrained to optimize the model according to the tool structure and the impact of the formation and borehole within the effective detection ***,the method is applied to a neutron porosity tool for *** various complex simulation environments,the maximum relative error between the calculated porosity results of Monte Carlo and FFCM was 6.80%,with a rootmean-square error of 0.62 *** field well applications,the formation porosity model obtained using FFCM was in good agreement with the model obtained by interpreters,which demonstrates the validity and accuracy of the proposed method.

关键词： Nuclear measurement Fast forward computation Volumetric constraints