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华东六省一市生物化学与分子生物学会联盟2019年学术与...

作者： Xia Liang Renxiang Xie Jinfeng Su Bingqi Ye Saisai Wei Zhibing Liang Rongpan Bai Zhanghui Chen Zhongxiang Li Xiangwei Gao Medical Research Institute & Guangdong Women and Children's Disease Precision Diagnosis and Treatment Engineering Technology Research CenterBaoan Maternal and Child Health HospitalJinan University Department of Public Health Zhejiang University School of Medicine

Background:Upregulation of RNA polymerase(Pol) Ⅲ products,including tRNAs and 5 S rRNA,in tumor cells leads to enhanced protein synthesis and tumor formation,making it a potential target for cancer treatment.In this study,we evaluated the inhibition of Pol Ⅲ transcription by triptolide and the anti-cancer effect of this drug in colorectal tumorigenesis.Methods:The effect of triptolide on colorectal cancer development was assessed in colorectal cancer mouse models,3 D organoids,and cultured cells.Colorectal cancer cells were treated with triptolide.Pol Ⅲ transcription was measured by realtime quantitative polymerase chain reaction(PCR).The formation of TFⅢB,a multi-subunit transcription factor for Pol Ⅲ,was determined by chromatin immunoprecipitation(ChIP),co-immunoprecipitation(Co-IP),and fluorescence resonance energy transfer(FRET).Results:triptolide reduced both tumor number and tumor size in adenomatous polyposis coli(Apc) mutated(ApcMin/+) mice as well as AOM/DSS-induced mice.Moreover,triptolide effectively inhibited colorectal cancer cell proliferation,colonyformation,and organoid growth in vitro,which was associated with decreased Pol Ⅲ target genes.Mechanistically,triptolide treatment blocked TBP/Brfl interaction,leading to the reduced formation of TFⅢB at the promoters of tRNAs and 5 S rRNA.Conclusions:Together,our data suggest that inhibition of Pol Ⅲ transcription with existing drugs such as triptolide provides a new avenue for developing novel therapies for colorectal cancer.

关键词： triptolide Colorectal cancer RNA polymerase Ⅲ TFIIIB

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The Active Constituents of Tripterygium wilfordii and Their Pharmacological Actions andClinical Applicati

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Chinese Journal of Integrative Medicine 1995年第3期1卷 235-239页

作者：王翠娣郭玉璞 Department of Neurology Peking Union Medical College Hospital Beijing

ＴｈｅＡｃｔｉｖｅＣｏｎｓｔｉｔｕｅｎｔｓｏｆＴｒｉｐｔｅｒｙｇｉｕｍｗｉｌｆｏｒｄｉｉａｎｄＴｈｅｉｒＰｈａｒｍａｃｏｌｏｇｉｃａｌＡｃｔｉｏｎｓａｎｄＣｌｉｎｉｃａｌＡｐｐｌｉｃａｔｉｏｎＷａｎｇＣｕｉ－ｄｉ（王... 详细信息

ＴｈｅＡｃｔｉｖｅＣｏｎｓｔｉｔｕｅｎｔｓｏｆＴｒｉｐｔｅｒｙｇｉｕｍｗｉｌｆｏｒｄｉｉａｎｄＴｈｅｉｒＰｈａｒｍａｃｏｌｏｇｉｃａｌＡｃｔｉｏｎｓａｎｄＣｌｉｎｉｃａｌＡｐｐｌｉｃａｔｉｏｎＷａｎｇＣｕｉ－ｄｉ（王翠娣）ａｎｄＧｕｏＹｕ－ｐｕ（郭玉...

关键词： Gossypol triptolide Strong Inhibitory Action Good Therapeutic Effect Peking Union Medical College Hospital

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NGF-induced neuritogenesis is promoted by triptolide independent of MAPKs and PI3K/AKT pathways

NGF-induced neuritogenesis is promoted by triptolide indepen...

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中国生理学会第24届全国会员代表大会暨生理学学术大会

作者：钱燕静王晓民首都医科大学神经生物学系神经变性病教育部重点实验室

Nerve growth factor（NGF）is the essential neurotrophic factor for neuronal development and its functional decline is involved in neurodegenerative diseases.Here,we found that triptolide（T10）,an active compound from Traditional Chinese Medicine herb,Tripterygium Wilfordii Hook.f.（TWHF）,coordinately worked with the NGF to form an initial protrusive pattern,and later to maintain proper neurite outgrowth in PC12 cells.In addition,the protein level of growth associated protein 43（GAP-43）,a cellular marker of neuronal differentiation was also enhanced by T10 treatment on NGF-stimulated PC12 cells.Further mechanical investigation demonstrated that the effect of T10 on NGF-induced neuronal morphogenesis is independent of MAPKs and PI3K/AKT activation.The data suggest that T10 could be a promising small compound collaborating with NGF to restore neural network,although the exact mechanism is still need to be explored.

关键词： PC12 cells neuronal differentiation neurite outgrowth nerve growth factor（NGF） triptolide

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Therapeutical effect of triptolide on AD transgenic mouse model

Therapeutical effect of Triptolide on AD transgenic mouse mo...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Bing XIAO,Qi WANG,Yan ZHENG,Xiao-Min WANG~* Department of Physiology,Key Laboratory of the Neurodegenerative Disorders of the Chinese Ministry of Education Capital Medical University,No.10 Xitoutiao Street,Youanmen,Beijing 100069,China

＜正＞Objective Alzheimer’s disease（AD） is a progressive neurodegenerative disorder that affects the elderly. The etiology of AD is still unknown.However,a converging line of evidence indicates that brain inflammation induced by P-amyloid（Aβ） deposition is closely associated with the pathogenesis of this disease.triptolide（named as T10） is an extract from the traditional Chinese herb Tripterygium Wilfordii Hook F（TWHF）.It has been identified as the major component responsible for the immunosuppressive and anti-inflammatory effects of TWHF.Our previous study has elucidated that it provides neuroprotection for AD in vitro.The present study is to explore whether it has the therapeutical effect on AD in vivo.Methods 5XFAD transgenic mice model and its wild type control were intraperitoneally injected with T10 and NS,respectively.Morris water maze and immunohistochemistry assaying were performed to detect behavioral and histopathological changes in these mice mentioned above.Results（1） Behavior of 5XFAD transgenic mice treated with T10 has been improved in Morris water maze test.（2） Immunohistochemistry data indicated that T10 reduced the aggregation of Aβ.Conclusion triptolide（T10） has some therapeutical effects on AD.

关键词： Alzheimer’s disease triptolide 5XFAD transgenic mice

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Transdermal drug delivery of triptolide-loaded nanostructured lipid carriers: preparation, optimized, in vivo and in vitro evaluation

Transdermal drug delivery of triptolide-loaded nanostructure...

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2018年第十二届中国药物制剂大会

作者：顾永卫 Xiaomeng Tang Meng Yang Dishun Yang Jiyong Liu Department of Pharmacy Fudan University Shanghai Cancer Center Department of OncologyShanghai Medical College Fudan University College of Pharmacy Shandong University of Traditional Chinese Medicine Department of Pharmacy Changhai Hospital Second Military Medical University

triptolide（TPL）, the active ingredients of Chinese herbs Tripterygium wilfordii Hook. f.（TWHf）, are widely used in treating autoimmune and inflammatory diseases. However, the toxic and side effects of TPL in liver and spleen were reported frequently. Transdermal drug delivery system（TDDS） for TPL was better patient compliance and controlled release. However, the permeability of TPL was limited because of its poor solubility. So, loading TPL in nanoparticles is a strategy to improve its solubility. This present study was to develop and evaluate the triptolide-loaded nanostructured lipid carriers（TPL-NLCs） for TDDS. TPL-NLCs was prepared with emulsification technique and optimized by central composite design of a response surface methodology（CCD-RSM）. The optimized TPL-NLCs were spherical with the mean size of 139.6.0±2.53 nm. The encapsulation efficiency and drug loading were 97.15%±9.46 and 10.35%±1.12, respectively. Moreover, the in vitro release study showed that TPL-NLCs had a sustained release profiles and the in vitro penetration study indicated that TPL-NLCs could effectively penetrate into skin. Besides, the methodology of skin-blood synchronous microdialysis was established to evaluate the pharmacokinetics of TPL-NLCs in vivo and the results displayed that the TPL concentration in skin was higher than that in blood. And TPL-NLCs presented a remarkable effect of decreasing knee edema, inhibiting inflammation by regulating the levels of TNF-α, IL-1β and IL-6, which indicated that TPL-NLCs was a promising topical administration in treatment of edema and inflammation associated with rheumatoid arthritis（RA）.

关键词： triptolide nanostructure lipid carriers CCD-RSM transdermal drug delivery skin-blood synchronous microdialysis anti-rheumatoid arthritis

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Preparation and in vitro antitumor activities of triptolide and cyclopamine loaded polymeric micelles

Preparation and in vitro antitumor activities of triptolide ...

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2018年第十二届中国药物制剂大会

作者：刘德俊 Di Zhang Yixue Pei Yongjie Liu Lingyun Xu School of Biology and Pharmaceutical Engineering Wuhan Polytechnic University

Objective: In order to overcome the poor solubility of triptolide(TP) and cyclopamine(CPA), enhance their anticancer effects, and decrease their side effects, triptolide and cyclopamine encapsulated polymeric micelle system(TP/CPA-PM) was prepared and its in-vitro antitumor activities were investigated. Methods: Self-prepared PEG-PLC was used as a carrier material to prepare a novel polymeric micelle system containing both TP and CPA(TP/CPA-PM;TP:CPA = 1:1, w/w) using acetone solvent evaporation method. The micelles were characterized in terms of particle size, analyzed by laser particle size analyzer, entrapment efficiency, determined by high-performance liquid chromatography(HPLC), and in-vitro drug release, determined by combining dialysis method with HPLC. The MTS assay was performed at different time points to determine the inhibitory effect of TP/CPA-PM and free-TP/CPA with different concentrations on the proliferation of three kinds of human pancreatic carcinoma cell lines, namely Miapace-2 cells, Kras cells and HPSC cells. Results: The average particle size of TP/CPA-PM(TP:CPA = 1:1, w/w) was(54.3±2.6) nm(n = 3), and the encapsulation efficiency of TP and CPA was(48.7±7.7%)(n = 3) and(58.9±6.0%)(n = 3), respectively. The drug release curve showed that TP in TP/CPA-PM demonstrated fast-release profile, while CPA in TP/CPAPM indicated sustained-release profile. The release of CPA from micelles was faster at pH 5.2 than at pH 7.4. After 24 h of incubation at 37 °C, 39.0% of CPA was released at pH 7.4, while 58.4% was released at pH 5.2. Compared with free-TP/CPA, TP/CPA-PM significantly inhibited the proliferation of the three kinds of pancreatic cancer cells in a dose-dependent and time-dependent manner. Conclusion: These findings indicate that the combination of triptolid and cyclopamine loaded in polymeric micelles is an effective strategy to treat pancreatic tumors.

关键词： triptolide cyclopamine polymer micelles encapsulation efficiency in-vitro release profile pancreatic cancer cells

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西北农林科技大学生命科学学院研究团队发现小分子药物triptolide诱导细胞自噬的新机制

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西北农业学报 2016年第1期25卷 33-33页

作者：黄海瀛西北农林科技大学生命科学学院

2015年12月29日,Oncotarget杂志（IF=6.359）在线发表西北农林科技大学生命科学学院雷鸣教授课题组的最新研究成果“triptolide induces protective autophagy through activation of the CaMKKβ-AMPK signaling pathway in prostate c... 详细信息

关键词： triptolide 细胞自噬 Tripterygium 雷公藤 protective 生命科学 AMPK 活性成分农业杀虫剂小分子药物

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Traditional Chinese Medicine

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China Medical Abstracts(Internal Medicine) 2015年第1期32卷 6-12页

2015012 Effect of Shenluotong decoction on renal interstitial fibrosis in rats with obstructive nephropathy.WANG Zheng(王筝),et al.Integr Tradit Chin&West Med Coll,Shijiazhuang 050091.Chin J Integr Tradit&West Med 2014;34(10):1238-44.Objective To observe the effect of Shenluotong Decoction(SD)on serum levels of aldosterone,monocyte chemoattractant protein-1(MCP-1),α-smooth

关键词： decoction interstitial aldosterone 王筝 simvastatin monocyte inhibit triptolide creased immunity

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雷公藤甲素致大鼠横纹肌溶解的实验研究

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中华急诊医学杂志 2013年第6期22卷 597-599页

作者：章梅华陈艳杨志海洪东升赵青威浙江大学医学院附属第一医院药剂科杭州310003 浙江工业大学药学院

中药雷公藤药材及其制剂在临床广泛用于类风湿性关节炎、肾病综合征、银屑病、湿疹样皮炎及其他自身免疫性疾病的治疗，而雷公藤甲素（雷公藤内酯醇，triptolide，TP）是从雷公藤根皮中提取的一种具有松香烷结构的三环氧二萜内酯类化合... 详细信息

中药雷公藤药材及其制剂在临床广泛用于类风湿性关节炎、肾病综合征、银屑病、湿疹样皮炎及其他自身免疫性疾病的治疗，而雷公藤甲素（雷公藤内酯醇，triptolide，TP）是从雷公藤根皮中提取的一种具有松香烷结构的三环氧二萜内酯类化合物，具有多种生物活性[1]。现代研究表明，TP不仅有抗类风湿性关节炎作用，

关键词：雷公藤甲素横纹肌溶解抗类风湿性关节炎 triptolide 自身免疫性疾病实验大鼠雷公藤内酯醇

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雷公藤内酯醇对急性淋巴细胞白血病Molt4细胞系p15基因表达的影响

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中华内科杂志 2005年第4期44卷 301-302页

作者：傅海英沈建箴福建医科大学附属协和医院血液科福建省血液病研究所福州350001

雷公藤内酯醇（triptolide）是从福建省泰宁县产的雷公藤根皮中分离提取的有效成分，我所经实验及临床Ⅰ、Ⅱ期研究发现其对多种髓系及淋巴细胞白血病均有较好的疗效。近年来，研究表明triptolide具有多种抗肿瘤作用，小剂量triptolide... 详细信息

雷公藤内酯醇（triptolide）是从福建省泰宁县产的雷公藤根皮中分离提取的有效成分，我所经实验及临床Ⅰ、Ⅱ期研究发现其对多种髓系及淋巴细胞白血病均有较好的疗效。近年来，研究表明triptolide具有多种抗肿瘤作用，小剂量triptolide即可抑制多种肿瘤细胞的生长。但目前对triptolide抗白血病及其他肿瘤的精确的目标和分子机制仍不清楚。Zhao等报道triptolide能下调肺癌细胞中细胞周期素D、B、A的表达，提示triptolide可能通过细胞周期调控途径抑制肿瘤。本研究以p15基因异常甲基化而失活T-急性淋巴细胞白血病（T-ALL）细胞Molt4为对象，试图探究triptolide对细胞周期调控中的这一重要基因的影响，并对其机制进行了初步探讨。

关键词：雷公藤内酯醇急性淋巴细胞白血病 triptolide 基因表达 p15 细胞系细胞周期素D 抗肿瘤作用有效成分分离提取研究发现肿瘤细胞分子机制抗白血病肺癌细胞泰宁县福建省多种小剂量

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