重要药用唇形科植物腺毛中的活性天然产物研究

Discovery and utilization of bioactive substances of medicinal plants are a major research topic nowadays. Plant glandular trichomes, well known as “chemical factories” and “the first defense line” of plants against insect herbivores and pathogens, are the major sites for synthesis and accumulation of various types of functional natural products, which are also a rich source of bioactive compounds. Medicinal Labiatae plants have played an important role in domestic medical and pharmaceutical fields. These plants are rich in glandular trichomes but their accumulated natural products and biological functions are largely unknown. In our previous work, we pioneered the establishment of a brand new technology, laser microdissection in combination with cryogenic nuclear magnetic resonance and ultra performance liquid chromatography coupled with mass spectrometry (LMD-cryoNMR-UPLC/MS/MS) and the corresponding method, and realized the precise investigation on the defense chemicals accumulated in specific glandular trichomes of a number of plant species. Based on this, the current project aims to systematically investigate the natural products in the glandular trichomes of 6 to 8 selected Labiatae plants with important medicinal value. Qualitative and quantitative analyses, isolation, identification, and enrichment of these natural products will be carried out. Major trichome natural products will be subjected to anti-microbial, anti-insect, and extensive related pharmacological assay subsequently. The results of this project are expected to reveal the defense chemicals in the glandular trichomes of these important medicinal plants. Discovery of bioactive natural products with application potential is also anticipated, thus providing target molecules for deep new drug or pesticide research and development, and also scientific basis for the rational and sustainable utilization of these important medicinal plant resources.

药用植物活性物质的发掘和利用是当前研究的重点。植物腺毛被誉为“化学工厂”，是合成和贮存各种类型和功能天然产物的重要场所，是植物抵御病虫害进攻的“第一道防线”，其中蕴含了丰富的天然活性物质。唇形科药用植物在我国医药领域具有重要地位，富含腺毛，但其中的天然产物及生物活性大多未知。前期首次建立了激光显微切割-超低温核磁共振-超高压液相色谱/质谱联用新技术方法，成功实现了对多种植物腺毛中的化学防御物质的精确研究。本项目拟选取6-8种重要唇形科药用植物，系统开展其腺毛中的天然产物分析、分离、鉴定和富集，对主要天然产物进行抗微生物和抗虫生物功能测定以及广泛的药理活性筛选，揭示腺毛中的化学防御物质，发现有应用前景的天然活性物质，为创新天然药物或农药研究提供目标活性分子，并为这些重要的药用植物资源的合理持续利用提供科学依据。

本项目运用光学显微镜和扫描电镜，对10种唇形科药用植物（痢止蒿、血见愁、肾茶、甘西鼠尾草、丹参、白毛火把花、秀丽火把花、狭叶红紫珠、抽葶锥花、宽管花）腺毛的形态和分布进行了研究。运用LMD-UPLC/MS/MS等技术方法，分析了上述10种植物腺毛中的特异天然产物，对其中9种植物腺毛的天然产物进行了定位、跟踪分离和结构鉴定，共鉴定腺毛天然产物25个，其中新化合物6个，包括1个分子内[2+2]环加成的6/6/5/4新颖骨架海里曼烷二萜。进一步对上述8种植物以及唇形科药用植物假秦艽、米团花和火把花的天然产物进行了系统研究，还分离鉴定241个化合物，其中新化合物77个，包括2个Me-30参与环化的6/6/6/6新颖骨架四环三萜皂苷。发现痢止蒿、肾茶和抽葶锥花腺毛中二萜具有昆虫防御功能，白毛火把花腺毛中二萜具有抗紫外和抗冷冻功能。此外，发现37个化合物具有免疫调节、乙酰胆碱酯酶抑制、减脂、抗耐药菌、肿瘤细胞毒等生物活性，值得深入研究的活性化合物3个，并发现米团花腺毛天然产物leucosceptroid B的减脂活性和初步作用机制。从米团花腺毛转录组中鉴定了催化合成大环二倍半萜和二萜的萜类合酶和雪松醇合酶，实现其异源合成，并发现大环二倍半萜的免疫抑制活性和初步作用机制。受邀在Natural Product Reports分别发表植物腺毛天然产物和植物二倍半萜研究长篇综述。部分结果已发表带标注的SCI论文15篇，其中IF>10论文3篇，IF>6论文3篇；获授权发明专利1项，申请发明专利3项；项目负责人入选国家“万人计划”领军人才，云南省“兴滇人才奖”，云南省劳模称号等；参加国内外学术会议交流报告11次；培养毕业博士5名和硕士2名。研究结果为相关药用植物资源的合理持续利用提供了重要科学依据，并为植物腺毛作为活性天然产物发现与生物合成研究的优良体系提供了有力证据。