宽叶匙羹藤中一个新的色原酮及其降血糖活性研究

A new chromanone component from Gymnema latifolium and its hypoglycemic activity

关键词:  宽叶匙羹藤, 化学成分, 色原酮, calomembranone L, 降血糖活性

Key words:  Gymnema latifolium, chemical constituents, chromanone, calomembranone L, hypoglycemic activity

摘要:

宽叶匙羹藤在傈僳族的药名为“片鲁爪”,民间常用于糖尿病的治疗。为探究宽叶匙羹藤(Gymnema latifolium)的化学成分及其降血糖活性,该研究综合运用大孔树脂、硅胶、MCI、Sephadex LH-20柱色谱和半制备高效液相色谱等多种分离方法对宽叶匙羹藤乙酸乙酯部位的化学成分进行分离纯化,结合质谱(MS)、核磁共振(NMR)谱及电子圆二色(ECD)谱等方法确定化合物的结构,采用基于HepG2细胞对葡萄糖摄取的方法评价分离所得化合物的体外降血糖活性。结果表明:(1)从乙酸乙酯部位中分离得到15个化合物,分别为calomembranone L(1)、calopolyanic acid(2)、blancoic acid(3)、apetalic acid(4)、isoapetalic acid(5)、apetalic acid methyl ester(6)、isoapetalic acid methyl ester(7)、calopolyanolide B(8)、2-羟基呫吨酮(9)、异胡椒酮 B(10)、lacexanthone(11)、caledonixanthone Q(12)、(7,8-cis-8,8'-trans)-2',4'-二羟基-3,5-二甲氧基-落叶松脂素(13)、(7R,8S)-去氢双松柏醇(14)、(+)-松脂醇(15)。其中,化合物1为新的色原酮类化合物,其余化合物均为首次从匙羹藤属植物中分离得到。(2)降血糖活性实验结果表明,在无显著细胞毒性的浓度下,化合物1、2、3、8、13的HepG2细胞对葡萄糖摄取量分别是对照组的1.47倍、1.47倍、1.12倍、1.49倍和1.23倍,且细胞活力维持在90%以上,这说明以上化合物具有促进HepG2细胞对葡萄糖的摄取作用。该研究结果丰富了宽叶匙羹藤的化学成分库,初步阐明了其降血糖的药效物质基础,为其进一步开发与应用提供了理论依据。

Abstract:

Gymnema latifolium, referred to as “Pian Lu Zhao” in the Lisu ethnic group, is traditionally employed to treat diabetes mellitus. To explore the chemical constituents and hypoglycemic activity of G. latifolium, this study employed a combination of macroporous resins, silica gel, MCI, Sephadex LH-20 column chromatography, and semi-preparative high-performance liquid chromatography to isolate and purify the chemical constituents from the ethyl acetate fraction of G. latifolium. The structures of the compounds were determined by mass spectrum(MS), nuclear magnetic resonance(NMR)spectroscopy, and electronic circular dischroism(ECD)spectroscopy. The in vitro hypoglycemic activities of the isolated compounds were assessed using glucose uptake assay based on HepG2 cells. The results were as follows:(1)Fifteen compounds were isolated and identified as calomembranone L(1), calopolyanic acid(2), blancoic acid(3), apetalic acid(4), isoapetalic acid(5), apetalic acid methyl ester(6), isoapetalic acid methyl ester(7), calopolyanolide B(8), 2-hydroxy-xanthone(9), isocudraniaxanthone B(10), lacexanthone(11), caledonixanthone Q(12),(7,8-cis-8,8'-trans)-2',4'-dihydroxy-3,5-dimethoxy-lariciresinol(13),(7R,8S)-dehydrodiconiferyl alcohol(14),(+)-pinoresinol(15). Among them, Compound 1 was a new chromanone compound, and compounds 2-15 were isolated from Gymnema plants for the first time.(2)Hypoglycemic activity assays showed that compounds 1, 2, 3, 8 and 13 increased glucose uptake to 1.47, 1.47, 1.12, 1.49 and 1.23 times that of the control group in HepG2 cells, respectively, while exhibiting minimal cytotoxic effects, maintaining cell viability above 90%. This indicated that the above compounds had effects of promoting glucose uptake by HepG2 cells. This study enriches the chemical profile of G. latifolium and preliminarily clarifies the material basis for its hypoglycemic effect, providing a theoretical foundation for its further development and application.