云南蒲桃属植物抗糖尿病活性成分研究

Diabetes mellitus (DM), as the third prevalent disease followed by cancer and cardiovascular disease, threatens people’s health heavily. The existing medications display undesirable side effects such as hypoglycemia, ketonuria, lactic acidosis, and obesity. Therefore, it is very urgent to develop new natural antidiabetic medicine with lower side effects. For so long, the plant extracts from Syzygium have been applied to cure DM in Southeast Asian countries such as India. We have researched the chemical constituents and their antidiabetic activity of 2 species of Syzygium and discovered that their extracts and some of constituents showed obvious α-glycosidase inhibition activities. Previous researches demonstrated that the major constituents in this genus were triterpenoids, flavones, and tannin. Obviously, it is necessary to further investigate their chemical constituents. 33 species of genus Syzygium were distributed widely in Yunnan Province, however, most of which have not been researched so far. This project focuses on the chemical constituents and their antidiabetic activities of 5 species of genus Syzygium in Yunnan Prefecture so that we understand the mainly antidiabetic constituents, obtain some promising compounds with significant antidiabetic activities, and investigate their structure-function relationship. This will be greatly in favour of the development, application, and protection of genus Syzygium plants in Yunnan Province. Meanwhile, it is also agreement with biology medicine strategy in Yunnan Province.

糖尿病是仅次于肿瘤和心血管疾病威胁人类健康的第三大疾病。现有降糖药容易引起低血糖、酮尿、乳酸酸中毒、肥胖等严重副作用。寻求副作用小、易于接受、来源于植物的天然抗糖尿病药物一直是研究的热点。几百年来，印度等东南亚国家就有用蒲桃属植物提取物治疗糖尿病的传统。基于此，我们对2种滇产蒲桃属植物提取物进行了抗糖尿病活性筛选，发现均显示出α-葡萄糖苷酶抑制活性。文献调研表明，该属植物化学成分研究报道不多、不够深入，主要为三萜和黄酮、鞣质等酚性成分，有待进一步挖掘。云南蒲桃属植物资源丰富，少有研究报道，本课题拟在前期活性筛选及初步化学成分研究基础上对5种滇产蒲桃属植物进行系统的化学成分及抗糖尿病活性研究。旨在阐明其抗糖尿病物质基础，寻找抗糖尿病活性化合物，探讨其构效关系及初步作用机制，为进一步研发抗糖尿病新药提供参考；为保护和利用云南这一宝贵植物资源提供依据。也与云南省生物医药作为新兴战略产业相契合。

蒲桃属植物具有悠久的药食兼用历史，几个世纪以来印度、印度尼西亚、马来西亚、菲律宾等东南亚国家就有用蒲桃属植物及其提取物治疗糖尿病。前人研究表明，该属植物主要化学成分为黄酮、三萜、单宁和苯丙素类化合物，具有降糖、α-葡萄糖苷酶抑制活性和提高胰岛素敏感性等活性。云南蒲桃属植物资源丰富，有33种，但多数未曾研究。本课题在对植物浸提物活性粗筛的基础上，对云南产7种蒲桃属植物滇南蒲桃（Syzygium austroyunnanense）、马六甲蒲桃（S. malaccense）、短药蒲桃（S. brachyantherum）和洋蒲桃（S. samarangense）、水蒲桃（S. jambos）、阔叶蒲桃（S. latilimbum）和水竹蒲桃（S. fluviatile）进行了系统的化学成分和抗糖尿病活性研究，共分离鉴定了266个单体化合物，其中46个间苯三酚衍生物，19个间苯二酚衍生物，12个漆树酸衍生物，99个三萜，18个黄酮。其中57个新化合物，43个新间苯三酚，2个新间苯二酚，1个新漆树酸衍生物，8各新三萜，1个新的维生素A类二萜酯和1个新单萜苷。其中化合物22为首次报道的具双脂肪链的间苯三酚，化合物77–83为带C-23长脂肪酸链的乌苏烷型和齐墩果烷型的三萜为首次从蒲桃属植物中分离得到，首次从蒲桃属植物中发现维生素A型单环二萜酯。42为首次报道其NMR数据。α-葡萄糖苷酶抑制活性筛选预示蒲桃属植物抗糖尿病活性很可能与该属植物中所含间苯三酚、间苯二酚及漆树酸衍生物相关。间苯三酚衍生物构效关系以及表明，苯环侧链中碳碳双键为活性必需官能团，苯环上羟基有利于活性的增强，C-5'甲基减弱其活性，有趣的是，同时具有C-5'甲基和C-6'甲氧基反而增强其活性；同时，苯环侧链上碳碳双键的数目和位置也对其活性有影响。漆树酸苯环侧链1个碳碳双键活性最强；间苯二酚苯环侧链上碳碳双键的数目和位置也对其活性有影响。该项目研究成果极大地丰富了蒲桃属植物化学及生物活性研究内容，加深了蒲桃属植物抗糖尿病活性物质基础的理解，为云南省该属植物的保护及开发利用提供了科学依据，具有良好的应用前景。上述研究成果以通讯作者名义发表SCI研究论文5篇，已接受发表SCI论文2篇；已受理专利申请1项(申请号201911244467.X)。