球蕊和狭叶五味子中的功能成分及其作用机制研究

AIDS and neurodegenerative diseases are one of most serious diseases for human health. Searching biological constituents and lead compounds from rich medicinal plant sources in China, and discovering novel drug candidates with good effects, low toxicity and side effects, and unique and definite mechanism; and then developing new drugs with independent intellectual property are one of the eternal and important research topic for Chinese pharmaceutical and scientific researchers. Plants in the family Schisandraceae, one of important group of medicinal plants, have been systemly studied by our group for more than 10 years, and a series of significant progress and some rich experiences have been got. Based on the previous research results, two species of this family, which have not been deeply studied and contains rich secondary metabolites, will be selected to study, and discover novel compounds with anti-HIV-1 and anti-neurodegenerative activities and their related mechanism. In addition, this project will deeply study the structure-activity relationships and mechanism of anti-HIV-1 activity of nigranoic acid, which has been isolated and found that this compound can inhibit the bonding of HIV integrase and viral DNA. What's more, this project will provide scientific evidence for discovering novel anti-HIV-1 candidates.

艾滋病和神经退行性疾病是危害人类健康最严重的疾病之一。从我国丰富的药用植物中寻找活性成分和先导化合物；发现疗效好、毒副作用低、作用机制独特而明确的候选药物，进而创制我国有自主知识产权的新药，是我国医药科技工作者永恒的、重要研究课题之一。在我们前期（10余年）对我国重要的药用类群植物－五味子科植物深入研究并取得很好进展和积累了丰富经验的基础上，本项目将对次生代谢成分异常丰富且还没有深入研究的两种五味子属植物进行抗HIV-1和神经退行性疾病的新型功能分子的发现和作用机制研究，特别是对前期已发现的对HIV-1整合酶（Integrase）与病毒DNA结合有很好抑制作用的尼格拉诺酸（nigranoic acid）进行构效关系和作用机制的深入研究，将为研发新作用机制抗HIV-1候选药物提供科学依据。

五味子科为我国重要的药用植物类群之一，前期研究中本研究组已对该科植物的次生代谢产物及其生物活性进行了深入研究并取得了较好进展与积累。本项目拟在前期研究基础上对球蕊五味子和狭叶五味子的次生代谢产物开展系统性的研究，同时以神经退行性疾病及抗HIV-1活性为重点，进一步探讨五味子科植物次生代谢产物的生物活性。. 目前，已从包括球蕊五味子和狭叶五味子在内的7种该属植物中发现了398个化合物，其中新化合物140个，包括8种新颖骨架类型。通过神经退行性相关模型筛选发现了部分化合物具有较强活性，并开展了相关作用机制研究，发现1个药物先导化合物，同时首次发现五味子降三萜类化合物具有抗凝血及抗血小板聚集活性。发表论文共计16篇（SCI论文15篇），其中学科前15%论文8篇，IF>6的论文6篇；一项PCT专利获授权。培养博士6名，硕士4名。通过该项目的实施进一步加深了对五味子科植物次生代谢产物的认识，丰富了SNTs的研究内容，同时拓展了该科植物次代谢产物，尤其是SNTs的生物活性范畴，为进一步开展对五味子科植物中新颖药物先导化合物的发现及创新药物研究奠定了较好基础。