Developing drugs from traditional medicinal plants

Developing drugs from traditional medicinal plants

从传统药用植物中开发药物

【摘要】每个文明的发展离不开医学，药用植物的发现和运用的效果有时远超于化学合成药。如今这些古老的知识和许多有价值的植物正以惊人的速度丧失。对传统医学的科学研究和药用植物的系统保护非常重要。本篇文章介绍了几种来自植物的重要处方药。

【关键词】麻黄碱；洋地黄；箭毒碱；长春碱；青蒿素

Over three quarters of the world's population relies mainly on plants and plant extracts for health care .Approximately one third of theprescription drugs in the US contain plant components, and more than 120 important prescription drugs are derived from plants. Most of these drugs were developed because of their use in traditional medicine. Economically, this represents $8000-10,000M of annual consumer spending. Recent World Health Organization (WHO) studies indicate that over 30 per cent of the world's plant species have at one time or another been used for medicinal purposes. Of the 250,000 higher plant species on Earth, more than 80,000 species are medicinal. Although traditional medicine is widespread throughout the world , it is an integral part of each individual culture. Its practice is based mainly on traditional beliefs handed down from generation to generation for hundreds or even thousands of years.Unfortunately, much of this ancient knowledge and many valuable plants are being lost at an alarming rate. The scientific study of traditional medicines and the systematic preservation of medicinal plants are thus of great importance.

在世界上有四分之三的人口主要依赖植物和植物提取物的保健护理。在美国大约有三分之一的处方药含有植物成分，超过120种重要的处方药来自于植物。大多是这些药的开发是因为在传统医药中的应用。在经济上，这代表有800-1000亿美元的年度消费支出。最近世界卫生组织（WHO）的研究表明，世界上超过30%的植物种类现在或以前做药用。在地球上250000种高等植物，药用的超过80000

种。虽然传统医学在世界范围内普遍存在，但它是每个文明中不可或缺的一部分。它的运用主要依据以传统的信仰世代相传从几百年甚至几千年。不幸的是，这些古老的知识和许多有价值的植物正以惊人的速度丧失。传统医药的科学研究和药用植物的系统保护是十分重要的。

For quite a long time, the only way to use plant medicines was either direct application or the use of crude plant extracts. With the development of organic chemistry at the beginning of this century, extraction and fractionation techniques improved significantly. It became possible to isolate and identify many of the active chemicals from plants. In the 1940s, advances in chemical synthesis enabled the synthesis of many plant components and their derivatives. In western countries, it was thought that chemical synthesis of drugs would be more effective and economical than isolation from natural sources. Indeed, this is true in many cases. However, in many other cases, synthetic analogues are not as effective as their natural counterparts. In addition, some synthetic drugs cost many times more than natural ones. Inspired by these realisations, coupled with the fact that many drugs with complex structures may be totally impossible to synthesise, there is now a resurgent trend of returning to natural resources for drug development.

很长一段时间，使用植物药的唯一途径是直接敷用或者使用粗植物提取物。随着本世纪初有机化学的发展，提取和分离技术有了显著的提升。它成为分离和鉴别许多来着植物的活跃化学物质的方法。在20世纪40年代，化学合成的研究发展促使许多植物成分及其衍生物的合成。在西方国家，人们认为化学合成药物比天然物质更有效和经济。实际上,在许多情况下，这是真实的。然而，在很多其他的情况下，合成类似物的效果不如天然来源的。此外，一些合成药物的成本比天然药物多许多倍。受这些事实，再加上很多具有复杂结构的药物根本不可能人工合成，现在有一个趋势开发天然药物。

Important prescription drugs from plants

Ephedrine is the oldest and most classic example of a prescription drug developed from a traditional medicinal plant. It is derived from Ma Huang , a leafless

shrub. Used to relieve asthma and hay fever in China for over 5000 years, it was introduced into western medicine in 1924 by Chen and Schmidt. Ephedrine is an alkaloid closely related to adrenaline, the major product of the adrenal gland. Pharmacologically, Ephedrine is used extensively to stimulate increased activity of the sympathetic nervous system. It is used as a pressor agent to counteract hypotension associated with anaesthesia, and as a nasal decongestant. The drug action o f this medicine is based both on its direct effect on α and β adrenergic receptors and on the release of endogenous noradrenaline.

来自植物的重要处方药

麻黄碱是从传统药用植物中开发的一种处方药是最古老和最典型的例子。它是源自于马黄,无叶的灌木。在中国用于缓解哮喘和花粉热有超过5000年，在1924年由陈和施密特引入到西方医学中。麻黄碱是与肾上腺素密切相关的一种生物碱，是肾上腺的主要产物。它用于麻醉引起的低血压的升压剂和鼻黏膜充血。这种药的药物作用基于对α和β肾上腺素能受体的直接作用和内源性去甲肾上腺素释放的作用。

Digitalis is one of the most frequently used medications in the treatment of heart failure and arrhythmia. It increases the contractility of the heart muscle and modifies vascular resistance. It also slows conduction through the atrioventricular node in the heart, making it useful in the treatment of atrial fibrillation and other rapid heart rhythms.

洋地黄是一种最常见的用于治疗心率衰竭和心律失常的药物。它增加心肌收缩力和改变血管阻力。它也减慢通过心脏与心室的节点，使它有益于治疗心房颤动和其他快速心脏节律。

Digitalis is found in the leaves and seeds of Digitalis purpurea and Digitalis lanata, commonly known as the foxglove plant. Foxglove has been used in traditional medicine in many parts of the world - by African natives as arrow poisons, by the ancient Egyptians as heart medicine, and by the Romans as a diuretic, heart tonic, emetic and rat poison. The Chinese, who found this ingredient not only in plants but

also in the dry skin and venom of the common toad, used it for centuries as a cardiac drug. In the western world, the foxglove was first mentioned in 1250 in the writing of a physician, Walsh, and it was described botanically in the 1500s.

洋地黄的叶子和种子分为紫花洋地黄和毛花洋地黄，俗称毛地黄植物。在世界上许多地方毛地黄已经用于传统医药——被非洲土著用于箭头毒药，被古埃及人用于治疗心脏病药，被罗马人作为一种利尿剂，心脏补品，催吐药和鼠药。中国人发现这种成分除了植物中以为，晒干的蟾蜍毒囊，几百年来用于治疗心脏的药物。在西方世界，16世纪洋地黄第一次提到是在一位沃尔什医生植物学描述中。

Digitalis is a glycoside containing an aglycone, or genin, linked to between one and four sugar molecules. The pharmacological activity resides in the aglycone, whereas the sugar residues affect the solubility and potency of the drug. The aglycone is structurally related to bile acids, sterols, sex hormones and adrenocortical hormones.

洋地黄是一种糖苷含有配基或配基与一个和四个糖分子链接。药理活性存在于苷元，而糖残影响药物的溶解性和效价。与苷元结构相关的有胆汁酸、甾醇类、性激素、肾上腺皮质激素。

d-Tubocurarine and its derivatives are the most frequently used drugs in operating rooms to provide muscle relaxation and prevent muscle spasm. These agents interrupt the transmission of the nerve impulse at the skeletal neuromuscular junction. Curare, the common name for South American arrow poisons, has a long and interesting history. It has been used for centuries by Indians along the Amazon and Orinoco rivers for hunting. It causes paralysis of the skeletal muscles of animals and finally results in death. The methods of curare preparation were a secret entrusted only to tribal doctors. Soon after their discovery of the American continent, European explorers became interested in curare. In the late 16th century, samples of native preparations were brought to Europe for investigation. Curare, an alkaloid , was found in various species of Strychnos and certain species of Chondrodendron. The first use

of curare for muscle relaxation was reported in 1942 by Griffith and Johnson. This drug offers optimal muscular relaxation without the use of high doses of anaesthetics. It thus emerged as the chief drug for use in tracheal intubation and during surgery.

右旋筒箭毒碱及其衍生物是最常见使用于手术室提供肌肉放松，防止肌肉痉挛的药物。这些药物阻断肌肉神经传输的神经冲动。Curare,通用名称为南美洲箭头毒药,具有悠久的历史。它已经被印度人使用了几个世纪沿亚马逊河和奥里诺科河的狩猎。它会导致动物骨骼肌麻痹，最终导致死亡。箭毒碱的制备方法是一个秘密只有委托部落的医生制作。不久后发现美洲大陆，欧洲冒险家对这种箭毒很感兴趣。16世纪末本土样品准备被带到欧洲做调查。箭毒，生物碱被发现在不同种类的马钱属和某些种类的南美防己属。由格里菲思和约翰逊在1942年箭毒首次使用肌肉松弛。因此，它是气管插管和手术中使用的主要药物。

Vinblastine and vincristine are two of the most potent antitumour drugs. They are obtained from Catharanthus roseus, commonly known as the rosy periwinkle. This plant, indigenous to Madagascar, is also cultivated in India, Israel and the US. It was originally examined for clinical use because of its traditional use in treating diabetis. The leaves and roots of this plant contain more than 100 alkaloids。Fractionation of these extracts yields four active alkaloids: vinblastine, vincristine, vinleurosine and vinresidine.These alkaloids are asymmetric dimeric compounds referred to as vinca alkaloids, but of these, only vinblastine and vincristine are clinically important antitumour agents.These two alkaloids are cell-cycle specific agents that block mitosis (cell division). Vincristine sulphate is used to treat acute leukaemia in children and lymphocytic leukaemia. It is also effective against Wilm's tumour, neuroblastoma，rhabdomyosarcoma (tumour of voluntary or striped muscle cells), reticulum cells sarcoma and Hodgkin's disease. Vinblastine sulphate is used in the treatment of Hodgkin's disease, lymphosarcoma, choriocarcinoma, neuroblastoma, carcinoma of breast, lung and other organs, and in acute and chronic leukaemia .

长春碱和长春新碱是最有效的抗肿瘤药物。它们来自于长春花，俗称长春花属。这种植物原产于马达加斯加，在印度、以色列和美国也有种植。它起初的临

床应用是传统方式治疗糖尿病。这种植物的根和叶中含有超过100种生物碱。这些提取物分离得到四活性生物碱：长春碱，长春新碱，环氧长春碱和异长春碱。这些生物碱的不对称二聚化合物称为长春花生物碱，但这些，只有长春碱和长春新碱是临床上重要的抗肿瘤药物。这两种生物碱是细胞有丝分裂（细胞分裂）周期特异性因子。硫酸长春新碱用于治疗儿童急性白血病和淋巴细胞性白血病。它也能有效预防肾母细胞瘤，神经母细胞瘤，横纹肌肉瘤（自发或横纹肌细胞瘤）、网状细胞肉瘤、霍奇金氏病。硫酸长春碱用于治疗霍奇金病、淋巴肉瘤、绒毛膜上皮癌、神经母细胞瘤、乳腺癌、肺和其他器官，急性和慢性白血病。Emerging plant medicines

Artemisinin is the most recent anti-malaria drug developed from plant-based traditional medicine. It is isolated from the leaves and flowers of Artemisia annua L. (Compositae), commonly known as the sweet wormwood, a cousin of tarragon. Indigenous to China, the extract of this plant is traditionally known as the qinghao. It has been used to treat malaria in China for over 2000 years. Its active component, artemisinin, was first isolated in the 1970s by Chinese scientists. Unlike quinine and chloroquine, this compound is non-toxic, rapid in effect, and safe for pregnant women. Furthermore, it is effective against chloroquine-resistant Plasmodium falciparum malaria and in patients with cerebral malaria. It kills the parasites directly so parasitaemia is quickly controlled. This work was confirmed by the WHO in Africa and other parts of Southeast Asia.

新兴的植物药

青蒿素是从植物中药最新研制的抗疟药物。它是从叶子和黄花蒿花分离出来的（菊科）俗称青蒿、龙蒿的亲属。在中国，这种植物的提取物传统上被称为青蒿。在中国2000多年来，它一直被用来治疗疟疾。青蒿素的活性成分，在20世纪70年代由中国科学家首次分离。不像奎宁和氯喹，这种化合物是无毒的，对孕妇安全且快速有效。此外，它能有效对付抗氯喹的恶性疟原虫疟疾患者和脑型疟疾。它能直接杀死寄生虫所以能迅速控制寄生虫。这个效果在非洲的WHO 和东南亚部分地区得到确认。

Artemisinin is an endoperoxide of the sesquiterpene lactone. The structure of this compound is too complex to be synthesised effectively. Artemisia is also found in many parts of the US, abundantly along the Potomac River in Washington DC, but the drug content of these varieties is only about half that of the Chinese variety. Currently, the WHO and the US are jointly engaged in the cultivation of Chinese Artemisia for worldwide use. The recent development offers renewed hope for using traditional medicine to provide new drugs for future medicines.

青蒿素是一种过氧化物的倍半萜内酯。要合成有效的该化合物结构非常复杂。青蒿也在美国华盛顿沿波托马克河的许多地方大量发现，但是这些品种的药物含量只有约一半中国的品种。目前，WHO和美国共同从事在世界范围内种植中国蒿属植物。

Selected from Paul L Huang,Philip L Huang,Peter Huang et al.,Chem.Ind.(London), 1992,290~293

选自 Paul L Huang,Philip L Huang,Peter Huang et al。化学工业（伦敦），1992.290 ~ 293