纪念青蒿素30周年

2004年底,世卫组织在北京纪念Coartem 10周年,促使我们纪念青蒿素的生日或“生年”,因为青蒿素是中国医药卫生科学家从青蒿中获得的划时代发现和自主创新成果,而且全新结构和独特抗疟活性,从而改写了只有生物硷成分抗疟的历史。作者建议把1975年确定为青蒿素“生年”,是因为从分离纯化得到青蒿素结晶,到鉴定其结构、确定抗疟活性、验证抗疟疗效等延续了整个20世纪70年代,以其中某一事件（如某篇论文发表的年月）来确定青蒿素的“生日”或“生年”,显然都不会获得广泛认同。青蒿素的科学历程告诉我们蒿属几百种植物除青蒿外,尚未发现其它种含有青蒿素:蒿属植物乃至菊科中数以千计的各类化学成分,尚未发现青蒿素以外的成分具有抗疟作用:青蒿广泛分布全球北温带,但是只有中医有用于治疗疟疾经验;只有少数地区青蒿的青蒿素含量高、杂质少,具有工业生产价值,故应该充分认识青蒿道地性对种植业的指导意义,同时采取有力措施保护优良种质资源和生物多样性。防止青蒿素重蹈氯睦发生抗药性复辙应该是我们的优先考虑,开发具有中医药优势和特色的与Coartem 等效或更好的复方制剂是青蒿素二次开发的重点方向之一。     

黄花蒿轮作模式的研究

黄花蒿Ariemisia annua L.是菊科蒿属植物,为传统中药材,是青蒿素来源的唯一植物,青蒿素对治疗疟疾具有独特的疗效,2004年世界卫生组织确定青蒿类药物为抗疟首选药物.     

黄花蒿栽培研究进展

黄花蒿（Artemisia annua L.）因含有青蒿素（Arte misinin）而在药用植物中占有重要地位.青蒿素类药治疟效果明显,不仅是我国目前唯一被世界卫生组织认可的按西药标准研究开发的中药,也是我国仅有的两个被收入世界药典的中药之一.目前,WHO（世界卫生组织）对2004年的联合用药（ACTs）政策做了调整,确定了复方蒿甲醚等作为替代奎宁类的抗疟推荐用药,无疑将极大地促进对青蒿素的需求,就现阶段的技术而言,人工合成青蒿素尚不经济可行,仍然依靠从原植物中提取,蒿属几百种植物除黄花蒿外,尚未发现其它种含有青蒿素,蒿属乃至菊科植物中数以千计的各类化学成分,尚未发现青蒿素以外的成分具有抗疟作用.全世界70%的黄化蒿资源集中在我国,我国历来是青蒿素原料药品的最大供应者,随着青蒿素类药品用量的增加,野生黄花蒿植物资源已经极其匮乏,远不能满足市场需要,因此,人工种植黄花蒿将成为近几年内中药材栽培研究的热点之一,本文就黄花蒿栽培方面的研究情况进行综述,旨在推进其栽培研究进程,为开展人工种植黄花蒿药材基地奠定基础.     

青蒿素及其衍生物抗肿瘤研究进展

青蒿素(artemisinin)是目前最常用的抗疟特效药,尤其是脑型疟疾和抗氯喹疟疾。近年来发现青蒿素及其衍生物具有较强的抗肿瘤作用,关于青蒿素抗肿瘤作用机制,以及能否将其开发为抗肿瘤新药的研究已成为青蒿素研究的热点。1青蒿素发展史1971年,中医研究院发现青蒿乙醚提取物的中性部分具有显著的抗疟作用,1972年从青蒿中分离出了青蒿素,1973年青蒿素首次作为抗疟药应用于临床,1997年世界卫生组织(WHO)在马尼拉会议上制定了青蒿琥酯的标准剂量疗程,1999年WHO将青蒿琥酯和蒿甲醚列入国际药典之后,标志着我国独立创制的新药首次得到了国际承认…     

青蒿素、青蒿甲素和青蒿乙素的细胞定位

<正> 引言青蒿素(C_(15)H_(22)O_5)是近年来从菊科蒿属植物黄花蒿(Artemisia annua L.)中分离出来的一种高效、速效、低毒的抗疟有效成分,经实验证明它是一种新型倍半帖内脂,仅在黄花蒿体内合成,而蒿属其它种则尚未发现含有青蒿素。有关其药理、物化特性、临床、资源等     

青蒿道地药材研究综述

青蒿入药有2 000多年的历史,根据现代研究结果推断,1 700多年前的《肘后备急方》中所记治疗疟疾的青蒿应该来源于黄花蒿。基于本草资料从治疗暑热、截疟等方面,青蒿的道地产区应在历史上的荆州(今湖北)及其周边地区;从抗疟成分青蒿素含量高低的角度,青蒿道地产区应在重庆、广西及周边省份。研究表明:黄花蒿在秋季花盛开时采收,抗疟用青蒿素含量较高;黄花蒿放置半年后青蒿素可降解30%左右,一般需放置阴凉干燥处贮藏。野生黄花蒿具有丰富的遗传多样性,在试验田选育出的黄花蒿其青蒿素质量分数最高可达2%。     

青蒿化学成分生物合成、体内分析及药代动力学研究进展

青蒿为传统的清虚热要药,因其为抗疟特效药青蒿素的唯一天然产物来源而受到了全世界广泛的关注。除青蒿素外,青蒿还包含倍半萜、黄酮、香豆素、挥发油和多糖等其他化学成分,具有解热、抗炎、抗病原微生物、抗哮喘、抗氧化、抗肿瘤等多种药理活性。有些成分除自身具有药理活性外,还可通过不同的机制在体内吸收和代谢等环节协同增强青蒿素的抗疟活性。基于此,该文系统整理了青蒿有关的现代研究文献,归纳总结了青蒿的化学成分生物合成、体内分析和药代动力学等内容,以期全面了解青蒿化学成分的药代动力学特征,为我国青蒿资源的充分开发及临床利用提供参考。     

青蒿素及其前体化合物的提取分离与鉴定

青蒿素是我国药学工作者于 1 971年从植物黄花蒿 Artemisia annua L.叶中提取分离得到的一个具有过氧桥的倍半萜类化合物[1] 。由于青蒿素及其衍生物蒿甲醚、双氢青蒿素及青蒿酯钠具有高效低毒的抗疟活性 ,尤其对具有抗氯喹能力的脑疟和急性疟有效 ,因此 ,对青蒿素及其衍生物的研究已经引起了全世界药学工作者的关注。由于青蒿素的化学合成[2 ,3 ] 步骤繁多、难度较大、得率低、成本高等诸多因素 ,至今未能产业化生产 ,而从植物原料中提取分离青蒿素 ,用于生产青蒿素及其衍生物制剂成本仍然较高 ,因此 ,许多国家的科研工作者都试图通过生物…     

屠呦呦获国际生物医学大奖“拉斯克奖”

2011年度拉斯克奖日前揭晓, 80岁的中国中医科学院屠呦呦教授获得临床医学奖,以表彰其在青蒿素研究中的贡献。青蒿素是治疗疟疾的重要药物,挽救了全球,尤其是发展中国家数百万人的生命。青蒿素发现始于半个世纪前国家组织的抗疟疾药物研发“523任务”,于1967年5月23日启动了举国体制的抗疟新药研发,遍布全国60多个单位的500多名科研人员组成了抗疟新药研发大军。中国中医研究院中药研究所的屠呦呦教授是抗疟中药研究的关键人物之一。〖TP1.TIF;X-*2;Y*1,Z#]典籍记载青蒿确实可以治疗疟疾。但是大量实验发现,青蒿提取物抗疟效果并不理想,其他科研机构也得出类似结论。中国中医研究院中药研究所屠呦呦教授领导的课题组,经长期反复实验,首次采用乙醚为溶剂,制备出具有明显抗疟效果的青蒿提取物。用乙醚提取这一步,是保证青蒿素有效制剂的关键所在。在此基础上,她们与全国多个研究团队深入开展研究,蒿甲醚、复方蒿甲醚等青蒿素类抗疟药先后诞生,让人类利用青蒿素抗疟达到新高度。屠呦呦提出用乙醚提取,对于发现青蒿的抗疟作用和进一步研究青蒿都至关重要,这个贡献保证了整个研究的不断进展。     

青蒿、青蒿素及其衍生物治疗系统性红斑狼疮研究现状

正中药青蒿,为菊科植物黄花蒿 (Artemisia annua L.)的干燥地上部分,有清热解暑,除蒸,截疟的功效,用于暑邪发热、阴虚发热、湿热黄疸等。青蒿素(Artemisinine)是从植物黄花蒿叶中提取的有过氧基团的倍半萜内酯药物,于1972年由屠呦呦和她的同事在青蒿中提取。其衍生物有蒿甲醚、蒿乙醚、青蒿琥酯、双氢青蒿素等。青蒿与青蒿素的抗疟疗效已得到世界的广泛认可,2015年10月青蒿素的发现者屠呦呦获得诺贝尔生理学或医学奖,成为     

Discovery and Development of Artemisinin and Related Compounds

Artemisinin is isolated from the plant Artemisia annua, sweet wormwood, an herb employed in traditional Chinese medicine. Prof. You-you Tu discovered artemisinin in the 1960s, so she was awarded the 2015 Nobel Prize in Physiology or Medicine. Artemisinin and its semi-synthetic derivatives are a group of drugs that possess the most rapid action of all current drugs against Plasmodium falciparum malaria. In this review, the author investigated history on discovery of artemisinin, ethnopharmacology of Artemisia plants, chemistry and pharmacological activities of the relative compounds, and introduced Tu and other Chinese and world scientists’ contribution, development of artemisinin and the related compounds and registered and marketed artemisinin drugs in China, UK, and USA. The author also recalled the studies on the mechanism of action of artemisinins and artemisinin combination therapies and summed up the resistance issues. In Current Recommendations and the Global Plan for Insecticide Resistance Management in Malaria Vectors (GPIRM), that the WHO prevents the development and manages the spread of insecticide resistance is summarized in the technical basis for coordinated action against insecticide resistance: preserving the effectiveness of modern malaria vector control. Prof. Tu re-emphasized the artemisinin resistant on five principles to the WHO. She called on the world''s scientists to pay attention to the study of drug resistance, and hopes scientists to contribute to break resistance of artemisinins.     

The potential of Artemisia annua L. as a locally produced remedy for malaria in the tropics: agricultural, chemical and clinical aspects

The plant Artemisia annua L. (Asteraceae) is listed in the Chinese pharmacopoeia as a remedy for various fevers including malaria, and contains the well-established antimalarial compound artemisinin. In this study, a hybrid form of A. annua was successfully cultivated in Central Africa. The aerial parts of the plant contained 0.63-0.70% artemisinin per dry weight, and approximately 40% of this artemisinin could be extracted by simple tea preparation methods. Five malaria patients who were treated with A. annua tea showed a rapid disappearance of parasitaemia within 2-4 days. An additional trial with 48 malaria patients showed a disappearance of parasitaemia in 44 patients (92%) within 4 days. Both trials showed a marked improvement of symptoms. In our opinion, these results justify further examinations of the antimalarial effect of A. annua preparations.     

国内外青蒿素生产过程差异性比较

青蒿素是治疗疟疾的特效药,临床中已经使亿万患者摆脱了疾病的困扰。目前,青蒿素的获取途径主要有直接从青蒿中提取、化学合成和生物合成。本研究通过对比国内外青蒿素生产过程的差异,分析问题存在的原因,并提出自己的看法和建议,以期为青蒿进一步的研究提供参考。     

青蒿素的组织化学定位及其含量相关性研究

目的 确定青蒿素储存部位并为高青蒿素含量黄花蒿植株筛选提供选择指标。方法 应用组织化学方法确定青蒿素的储存结构，应用统计学方法确定储存结构腺毛状分泌腺密度与青蒿素含量的相关性。结果 青蒿素储存于腺毛状分泌腺(BGT)和T-型网状分泌腺(NTFT)中，在叶中腺毛状分泌腺的密度与青蒿素含量正相关。结论 腺毛状分泌腺密度可作为高青蒿素含量黄花蒿育种筛选指标。     

青蒿不同部位薄层鉴别比较研究

目的:通过收集青蒿植株不同部位的药材,对其主要化学成分进行定性研究,为黄花蒿药材资源的开发与利用奠定基础。方法:采用薄层鉴别法。结果:所建立的方法适用于青蒿不同部位的化学成分鉴别。结论:青蒿子、青蒿地上部分以及青蒿叶成分最为相似;花所含的挥发油种类最多,茎最少;茎可能不含或是含有极微量的青蒿素。其中,青蒿子、花、茎的薄层鉴别属首次报道。     

昭通产青蒿植物中青蒿素的分析研究

目的 :对昭通产青蒿进行质量分析。方法 :用 TL C- IR法鉴别青蒿中的青蒿素 ,用 TL C- UV法测定其含量。结果 :定性、定量方法简便、准确 ,花蕾中的青蒿素含量较高。结论 :本法可用于青蒿中青蒿素的分析研究     

Expanding the Therapeutic Spectrum of Artemisinin: Activity Against Infectious Diseases Beyond Malaria and Novel Pharmaceutical Developments

The interest of Western medicine in Traditional Chinese Medicine(TCM) as a source of drug leads/new drugs to treat diseases without available efficient therapies has been dramatically augmented in the last decades by the extensive work and the outstanding findings achieved within this kind of medicine. The practice of TCM over thousands of years has equipped scientists with substantial experience with hundreds of plants that led to the discovery of artemisinin(qinghaosu), which is extracted from the medicinal plant Artemisia annua L.(qinghao). The unexpected success of artemisinin in combating malaria has drawn strong attention from the scientific community towards TCM. Artemisinin was discovered by Youyou Tu in 1972. Since then, several novel pharmacological activities based on the well-known properties of the sesquiterpene lactone structure with the oxepane ring and an endoperoxide bridge have been unravelled. Beyond malaria, artemisinin and its derivatives(artemisinins) exert profound activities towards other protozoans(Leishmania, Trypanosoma, amoebas, Neospora caninum, and Eimeria tenella), trematodes(Schistosoma, liver flukes), and viruses(human cytomegalovirus, hepatitis B and C viruses). Less clear is the effect against bacteria and fungi. Based on the promising results of artemisinin and the first generation derivatives(artesunate, artemether, arteether), novel drug development strategies have been pursued.These included the synthesis of acetal-and non-acetal-type artemisinin dimeric molecules as well as developing nanotechnological approaches, e.g.artemisinin-based liposomes, niosomes, micelles, solid lipid nanocarriers, nanostructured lipid carriers, nanoparticles, fullerenes and nanotubes. The current review presents an overview on different aspects of artemisinins, including sources, chemistry, biological/pharmacological properties, types of infectious pathogens that are susceptible to artemisinins in vitro and in vivo, in addition to the advancement in their drug delivery systems utilizing pharmaceutical technology. It would be expected that different therapeutic strategies based on the second and third generation artemisinin derivatives and artemisinin-based drug technologies would be available in the near future to treat specific infectious diseases.     

Can ethnopharmacology contribute to the development of antimalarial agents?

The resistance of Plasmodium falciparum, the cause of tertian malaria, to synthetic antimalarials, together with the resistance of the vector mosquitoes to insecticides, has resulted in a resurgence in the use of quinine and a search for new antimalarial agents. In recent years, artemisinin, isolated from Artemisia annua which is used in Chinese traditional medicine for the treatment of malaria, has proved to be effective in the treatment of cerebral malaria due to chloroquine-resistant strains of P. falciparum. The development of in vitro tests utilising P. falciparum obtained from malaria patients means that it is possible to use bioassay guided fractionation of active extracts in order to isolate active principles. A number of laboratories throughout the world are currently investigating plants used in traditional medicine for their active constituents. Some of their results will be described and in particular two aspects of our investigations with species of Simaroubaceae and Menispermaceae will be discussed. There is every possibility that such approaches which use leads from Ethnopharmacology will result in the development of new antimalarial agents. It is vitally important to those populations relying on traditional medicines for the treatment of malaria that the safety and efficacy of such medicines be established, their active principles determined and that reproducible dosage forms be prepared and made available for use.     

RP-HPLC法测定青蒿中青蒿素的含量

目的建立青蒿(黄花蒿)干叶中青蒿素的含量测定方法,为甲醇提取青蒿素的工业化生产工艺提供依据。方法采用正交试验设计,优选测定条件,采用Shimadzu Shim-pack VP-ODS C18柱(250 mm×4.6 mm,5μm),流动相为乙腈-水(55∶45),流速为1.0 mL.min-1,检测波长为210 nm。结果最佳的含量测定条件为加40倍量甲醇,超声提取3次,每次50 min。青蒿素在1～40μg范围内与峰面积呈良好的线性关系(r=0.99998),平均加样回收率为99.8%,RSD为1.0%(n=6)。结论该方法简便、准确,适用于黄花蒿中青蒿素的含量测定。     

黄花蒿种质资源的RAPD分析

目的研究青蒿素高产的黄花蒿植株的遗传多样性特征。方法结合青蒿素量的测定,应用RAPD技术对10个产地黄花蒿进行遗传多样性分析。结果发现RAPD多态位点为53.6%,证明在黄花蒿野生群体中存在较丰富的遗传多样性。UPGMA分析表明:在黄花蒿中可能至少存在具有遗传分化的4个分支,黄花蒿遗传分化与青蒿素量的变化及地理分布有一定的相关性。结论黄花蒿具有明显的遗传分化,这些遗传分化是黄花蒿种质资源筛选的关键,是青蒿素“高量育种”和生物技术开发的基础。