华中地区叶下珠属植物新颖结构化合物的发现与生物活性研究

The plants of the genus Phyllanthus (Euphorbiaceae) are a class of important medicinal plants that widely distributed in most tropical and subtropical countries. There are more than thirty species of the genus that natively grow in Southern China, and most of them have long been used in folk medicine to treat kidney and urinary bladder disturbances, intestinal infections, diabetes, infantile malnutrition, and hepatitis B. Studies on the plants of the genus have increased considerably in recent years. Substantial progresses on their chemical and pharmacological properties, as well as several clinical studies of some Phyllanthus species have been carried out by medicinal chemists and pharmacologists. These studies carried out with the extracts and purified compounds from these plants led to the identification of A considerable pharmacological active natural products, including terpenoids, lignans, alkaloids, flavonoids, lactones, steroids, tannins, and so on. Furthermore, these isolated compounds further support most of their reported uses in folk medicine as an antiviral, in the treatment of genitourinary disorders, and as antinociceptive agents..In the past years, advanced technologies for isolation and analysis of the plants have revolutionized Phyllanthus researches, and an increasing number of novel lignans, triterpenoids and other natural products have been isolated and characterized. However, there is a fact that the different environmental conditions affect the chemical constitutions of the plants. Thus, it may be resonable to postulate that more structurally unique and bioactive secondary metabolites could be discovered. Based on the investigations reported previously, two Phyllanthus species collected from Huazhong area will be phytochemically investigated in this program. The chemical constituents will be determined through comprehensive spectroscopic methods, including IR, UV, MS, HRMS, 1D and 2D NMR spectrum, as well as CD and X-ray diffraction experiments. Consequently, the pharmacological properties of some chosen compounds will be evaluated for their cytotoxic activities against several human cancer cell lines, such as HL-60 (human leukemia), MCF-7 (breast cancer), and SW-480 (human pancreatic carcinoma) cancer cell lines by using the MTT method. Since the plants of the genus Phyllanthus have potential beneficial therapeutic actions in the management of various diseases, the study is important to discover more novel natural products for research into the structure-activity relationship, to the investigation on the mechanisms of action for these related bioactive compounds, and to provide more scientific evidences in favor of sustainable exploitation and utilization of the important resources of Phyllanthus for developing new drugs.

大戟科叶下珠属植物在我国约30余种，具平肝清热、利水解毒之效，可治肠炎、肾炎水肿、黄疸型肝炎、尿路感染、糖尿病及小儿疳积等，是一类重要的药用植物。肿瘤是危害人类健康的一类重要疾病，目前急需高效低毒、对多药耐药肿瘤细胞有效的抗肿瘤药物。前人研究发现该属植物中化合物结构类型十分丰富，且大都具有很好的生物活性。申请者前期研究中，对青灰叶下珠（P. glaucus）进行了初步的化学和药理学研究，发现其中木脂素和萜类成分具较强的肿瘤细胞毒活性。鉴于华中地区丰富的叶下珠属植物资源和独特的生境，完全有可能从中继续发现结构新颖、强生物活性的化合物。本项目拟对华中地区两种叶下珠属植物的主要化学成分进行研究，阐明其药效化学物质基础，为其质量标准的制定奠定理论和实践基础，为合理开发利用华中地区丰富的叶下珠属植物资源、发现药物先导化合物和开发具有我国自主知识产权的新药提供科学依据。

大戟科叶下珠属（Phyllanthus）植物在我国约30余种，具平肝清热、利水解毒之效，可治肠炎、肾炎水肿、黄疸型肝炎、尿路感染、糖尿病及小儿疳积等，是一类重要的药用植物。近年来，从该属植物寻找显著生物活性成分是天然产物研究的热点领域。该属植物的主要化学成分为木脂素和萜类等，具有抗肿瘤、抗炎、抗病毒、抗菌、抗氧化以及免疫调节活性等生物活性，特别是目前对其抗肿瘤和免疫调节活性的研究尤为活跃。..在本项目的资助下，完成了从华中地区采集的两种叶下珠属植物[叶下珠（P. urinaria）和青灰叶下珠（P. glaucus）]的植物化学成分和生物活性研究。分离鉴定了90个化合物：1)从叶下珠95%乙醇提取物中分离得到30个化合物，其中13个成分为首次从该植物中分离得到；2)从青灰叶下珠中分离并鉴定了60个化合物，含新化合物21个，包括木脂素、新木脂素类、二萜类等成分，部分化合物的结构为单晶X-ray所确证。有趣的是，通过多种溶剂系统和手性HPLC色谱柱的联合运用，成功实现了8对木脂素和新木脂素对映体的手性拆分。生物活性评价中，部分化合物显示一定的抗氧化和抗前列腺炎活性。发表SCI论文一篇，培养博士研究生3名，硕士研究生1名。本项目的执行，进一步丰富和拓展了叶下珠属植物化学成分研究，进一步阐明其药效化学物质基础，为合理开发利用我国叶下珠属植物资源提供了科学依据。