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中国鼠尾草属药用植物亲缘学研究

A Pharmacophylogenetic Study of Salvia L. (Lamiaceae) in China

【作者】 李旻辉

【导师】 肖培根; 陈建民;

【作者基本信息】 中国协和医科大学 , 生药学, 2008, 博士

【摘要】 唇形科鼠尾草属(Salvia L.)植物全世界大约有1000种以上,在全世界范围内存在着三个分布中心:中南美洲地区(500 spp.)、中亚—地中海地区(250 spp.)、东亚地区(100 spp.)。其中中国有84种,分布于全国各地,尤以西南为最多。鼠尾草属(Salvia L.)是一个重要的药用植物类群。Salvia来源于拉丁文salvare,意为治愈。早在几千年前该属多种植物就已成为重要的药用植物,用于治疗伤风感冒、呕吐、肺结核、癫痫、消化不良、心脏病、痛经等60多种疾病。由于中国鼠尾草属药用植物种类多、分布广、变异大,其系统分类、品种鉴定及资源利用一直十分混乱。为了更好的利用国产本属植物的药用资源,我们对中国鼠尾草属药用植物种类及药用情况作了调查与整理。调查和分类鉴定结果表明:中国地区分布的鼠尾草属药用植物共有43种(不包括变种),其中23种植物的根及根茎作为丹参使用。同时我们对丹参类药材的野生状况、种植及药材产销情况进行了实地调研。发现虽然全国丹参类药材种类众多,但正品丹参(S.miltiorrhiza)的种植与应用已经占据了丹参类药材的主导地位。中国鼠尾草属是一个比较复杂而又特殊的类群,遗传基因和东亚独特的地理环境决定本类群植物化学成分的特殊性。丹参酮类和咖啡酰缩酚酸类化合物在中国鼠尾草属植物中分布甚广,为该属植物的主要特征性化合物。而且这两类成分都具有很高的生物活性。探索这两类活性成分在本类群中的分布规律具有重要的意义。所以为了扩大本属药用植物资源和更加客观的评价本属药用植物的质量,我们开展了本项工作。一共收集了40种鼠尾草属植物,共计57个样品。利用HPLC-DAD法测定了样品中丹参酮类成分(丹参酮Ⅰ,隐丹参酮,二氢丹参酮Ⅰ,丹参酮ⅡA)和酚酸类成分(丹参素、原儿茶酸,原儿茶醛,咖啡酸,绿原酸,迷迭香酸,紫草酸,丹酚酸B,丹酚酸A)的含量。通过测定结果我们发现孤隔鼠尾草亚属宽球苏组(Euryspace)和荔枝草亚属丹参组(Drymosphace)中的植物广泛含有丹参酮类成分。而且丹参酮类成分主要分布在这两个类群植物的根部,地上部分中的含量较低,而在美洲鼠尾草亚属和鼠尾草亚属两个类群中植物中没有检测到四种丹参酮类成分中的任何一种成分。我们的实验结果首次从植物化学分类学的角度支持Bentham的分类系统对宽球苏组和丹参组的处理方式,同时也表明宽球苏组和丹参组这两个类群可能为一个单独的进化支(Clade)。酚酸类成分广泛分布在中国鼠尾草属植物中,但不同种类的酚酸在不同类群中分布却有明显差异。紫草酸和丹酚酸B广泛分布在中国鼠尾草属各个类群中,除了引种的美洲鼠尾草亚属植物中没有检测到这两类成分,其它三个亚属均有植物含有这两种成分,根据我们归纳的文献,国外鼠尾草类群中并没有发现此类成分的报道。如果我们把这两种成分含量加以考虑,就会发现在只有在荔枝草亚属丹参组的植物中,这两类成分极为丰富,其它类群中植物这两种成分或缺失或微量存在,丹酚酸B本属不同植物类群中呈间断分布可能使其具有潜在的分类学价值。此项研究对开发本属药用资源意义重大。我们又初步探讨了中国鼠尾草属亲缘关系、传统疗效和化学成分之间的联系,根据讨论结果发现虽然有个别物种根据形态特征被放在同一类群中,但它们的化学成分和疗效却与其所属类群中的其它植物相差甚远,我们推测这些物种形态学的某些相似性可能为趋同进化的结果。所以很有必要对我国鼠尾草属植物进行更广泛的植物化学、药用植物亲缘学及分子系统学方面的研究,为开发新的药用资源提供科学的理论依据。

【Abstract】 Salvia L. (family Lamiaceae) is a large genus of over 1,000 species widely dist ributed in tropical and temperate regions of the world, with 84 species native to China. The group is an extremely abundant medicinal plant source.Many species o f the genus have been used as medicinal plants for a long time. For example, Da nshen, the root and rhizome of Salvia miltiorrhiza Bunge, was one of the earliestand also the most commonly used herbal drug in practice of TCM.To investigate the resources and utilization of medicinal plants in Salvia from China, during the period of 2006-2007, we conducted six field surveys in 13 prov inces (Beijing, Hebei, Henan, Shandong, Anhui, Jiangsu, Zhejiang, Hubei, Shanxi, Gansu, Sichuan, Guangxi and Yunnan province). In concert with the local herbalis ts, we collected 40 species and 57 samples and recorded the detailed information of these medicinal plants including the local name, collecting location, growing en vironment, distribution and therapeutic effects. The Survey showed that 43 Salvia plants have been used as folk medicine for multiple therapeutic remedies in differ ent region of China, and 23 plants in the genus have been used as Danshen. Andwe found that all the investigated Danshen species belonged to sect. Euryspace S tib. or sect. Drymophace Benth.. Molecular systematic study also supported the re asonableness of using species from sect. Drymophace as substitute drug resources of Danshen. The distribution characteristic of Danshen species in the two groups was different. Danshen species from sect. Euryspace were mainly distributed in th e plateau area of 2500-4000 m above sea level in south-western China, and S. pr zewalskii in this group was widely used and has been commercially available in t he local herbal markets in south-western and north-western China. The geographic al distribution and resources of other Danshen species in sect.Euryspace were limi ted. And their folk applications were limited to remote mountain areas and minori ty region of south-western China. Most Danshen species in sect. Drymophace wer e distributed in the plain and hills of North China, East China and Central China, with only a few species extending to south-western and north-western China.Ethnopharmacologically, the medicinal plants in Sect.Drymosphace and Euryspha ce have been mainly used as medicines for promoting blood circulation to regulat e menstruation, activating meridian and collateral, and the medicinal plants in Sub g.Allagospadonopsis have been mainly used as medicines for clearing heat from b lood, which indicates that these plants may be a source for new medicines posses sing antibacterial activity , antiviral activity and antitumor activity.HPLC hyphenated with DAD detection was used for studying the distribution of tanshinones and polyphenolics in some Chinese Salvia species which we collected.According to the data, we found the distributions of tanshinones had some regula r pattern in the subgenus levels: tanshinones occurred frequently in the species of s ubg. Salvia and subg. Sclarea(Moench) Benth., while they were absent from the sp ecies in subg. Jungia (Moench) Brig. and Subg. Allagospadonopsis Briq.. We also f ound the species from Sect. Eurysphace Stib. were abundant in tanshinones, and the tanshinones almost occurred in all the investigated species of the group.As a result of this study, our data support the circumscription of the sect. Drymosphare as pro posed by Bentham. The distribution of tanshinones, therefore, provides a valuable c hemotaxonomic tool for determining infra-generic differences within the genus Salvi a. Polyphenolics, are also abundant in the Salvia, especially in Sect.Drymosphace a nd Sect.Eurysphace.However, the polyphenolics in samples were not the same entirel y; the contents of mutual polyphenolics varied greatly between the samples, and thi s may be due to both genetic and environmental influences. Additionly, our study a lso showed tanshinones and phenolic acids were abundant in different Danshen spec ies and provided an empirical base for their use in TCM.There were many problems in the systematic classification, variety identification a nd resources utilization of Chinese Salvia species. The plants in the group should b e paid much more attention. Further comprehensive studies (Phytochemistry, Pharma cophylogeny, Molecular Phylogeny) on these species are needed for their better med ical utilization.

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