基于发汗和止汗生物活性筛选的麻黄与麻黄根同源异效有效部位物质基础研究

"Same source, different effect" is a phenomenon in traditional Chinese medicine that for some herb drugs, though from the same plant, their clinical effects vary significantly when different parts are administered. With diaphoretic, anti-asthmatic and diuretic effect, ephedra is commenly used for the treament of cold and flu, lack of sweating, coughing, wheezing and edema. Ephedra root is antiperspirant, and is used for managing perspiration and hyperhidrosis. There is no satisfactory explanation and scientific theory for the cause of this "same source, different effect" phenomenon yet. Based on our earlier work, we will fully study ephedra and ephedra root, screen their diaphoretic and antiperspirant activities, and determine their active sites for each activity in this project. By using the modern technologies of soft ionization ESI-MS tandem mass spectrometry and chromatography instruments, we will perform complete chemistry screening of their active sites to isolate, characterize and determine the potency of the active diaphoretic and antiperspirant agents. We will also explore the mechanism of the diaphoretic and antiperspirant effects. This work will be very valuable for us to understand the "same source, different effect" phenomenon of ephedra from the molecular level, and to discover novel lead compounds. This work will also lay out the foundation for developing new diaphoretic and antiperspirant therapies from ephedra through modern Chinese medicine.

中药中存在一种现象，就是有的药物尽管来源于同一植物，但因其药用部位不同，而临床应用效果不同，即"同源异效"。麻黄是发汗、平喘、利水药, 用于治疗感冒风寒、表实无汗、咳嗽气喘和风水浮肿等病；而麻黄根是止汗药, 专治体虚自汗。目前国内外关于此现象的现代科学阐述尚处于空白。本项目在前期工作基础上，以麻黄和麻黄根为研究对象，以发汗和止汗活性为靶标进行活性筛选，确定麻黄及麻黄根中发汗和止汗有效部位，采用国内外领先的软电离ESI-MS串联质谱及色谱联机等技术对有效部位进行化学筛选，结合现代色谱学，现代波谱学快速分离并结构确定靶向发汗和止汗的生物活性成分，并对发汗和止汗作用机理进行探讨。本项目对于从现代分子水平解释麻黄"同源异效"现象，并发现新颖结构的先导化合物，均具有重要的学术价值，同时为从麻黄中开发出现代中医的"汗法要药"奠定基础。

中药中存在一种现象，就是有的药物尽管来源于同一植物，但因其药用部位不同，而临床应用效果不同，即“同源异效”。麻黄是发汗、平喘、利水药, 用于治疗感冒风寒、表实无汗、咳嗽气喘和风水浮肿等病；而麻黄根是止汗药, 专治体虚自汗。目前国内外关于此现象的现代科学阐述尚处于空白。本项目以麻黄和麻黄根为研究对象，以小鼠发汗和止汗活性为靶标进行活性筛选，确定了麻黄及麻黄根中发汗和止汗活性组分（5个），并结合现代色谱学、现代波谱学以及现代色谱-波谱联机技术，对活性组分进行了化学筛选，分离鉴定检测出 77个单体化合物（其中结构新颖的化合物 9个），同时对活性组分发汗和止汗作用机理进行了探讨，并采用GC-MS、TLC、HPLC、HPLC-MS等方法对其发汗、止汗物质基础进行了化合物及分子群表征，从而对传统中医所谓“麻黄发汗、麻黄根止汗”的同源异效现象给予了解释。此外，我们还通过体内外活性筛选，初步证实了麻黄根总黄酮及其所含单体化合物ephedrannin B有抑制肿瘤生长的作用。这些成果的取得将为进一步从麻黄与麻黄根中开发出创新靶向发汗和止汗药物，扩大麻黄根的临床应用范围，研制高效低毒的抗癌新药奠定基础。目前，本课题已申请国家发明专利 2 项，发表论文 3 篇（含已录用），获吉林省科技进步二等奖 1 项。