赤芝中新颖杂萜-三萜杂聚体的分离纯化及其改善C2C12细胞胰岛素抵抗作用  

Meroterpenoid-triterpenoid hybrids from Ganoderma lucidum and their biological activity against insulin resistance in C2C12 cells

作　　者：张娇娇 彭云丽 程永现 Zhang Jiaojiao;Peng Yuni;Cheng Yongxian(School of Pharmaceutical Sciences,Health Science Center,Shenzhen University,Shenzhen 518000,Guangdong,China)

机构地区：[1]深圳大学医学部药学院,广东深圳518000

出　　处：《生物医学转化》2023年第1期61-77,共17页Biomedical transformation

基　　金：国家自然科学基金项目(82030115);NSFC-云南联合基金项目(U1702287);国家杰出青年科学基金项目(81525026);深圳市基础研究项目(JCYJ20200109113803838)。

摘　　要：目的赤芝(Ganoderma lucidum)在民间被用于糖尿病治疗,但缺乏数据支撑,需探索其化学成分及其是否具有抗糖尿病作用以利于临床推广。方法采用多种分离技术,如MCI gel CHP 20P、RP-18、Sephadex LH-20、硅胶柱色谱、制备薄层色谱(Preparative Thin-Layer Chromatography,PTLC)和高效液相色谱(High Performance Liquid Chromatography,HPLC)等,对云南产赤芝的低极性成分进行研究,利用一维(One Dimensional,1D)和二维(Two Dimensional,2D)核磁共振波谱(Nuclear Magnetic Resonance Spectroscopy,NMR)等方法鉴定化合物结构,在C2C12细胞胰岛素抵抗体外模型中研究其活性。结果从云南2个产地赤芝中分离鉴定8个杂萜-三萜杂聚体类新化合物,ganolucinins D-K(1-8),其中化合物7和8可上调胰岛素受体底物1(Insulin Receptor Substrate 1,IRS1)和蛋白激酶B(Protein Kinase B,PKB/Akt)磷酸化,8可促进C2C12细胞葡萄糖摄取。结论赤芝中可能存在一系列杂萜-三萜杂聚体类化合物,其中化合物8具有改善胰岛素抵抗潜力,可能是灵芝抗糖尿病的药效物质之一。Objective Ganoderma lucidum is served for folk treatment of diabetes,however,due to the lack of supportive data,the exploration of its chemical composition and effects on anti-diabetes is needed for clinical promotion.Methods A variety of separation methods were used,such as MCI gel CHP 20P,RP-18,Sephadex LH 20 and silica gel column chromatography,PTLC and HPLC,to investigate the low-polarity components of Ganoderma lucidum produced in Yunnan province.1D and 2D NMR were used to elucidate the structures of the compounds,and their activities were examined in the insulin resistance model of C2C12 cells in vitro.Results Eight new meroterpenoid-triterpenoid hybrids,ganolucinins D-K(1-8),were isolated and identified from Ganoderma lucidum cultivited in two different areas in Yunnan province.Compounds 7 and 8 upregulate the phosphorylation of IRS1 and Akt,and compound 8 could promote glucose uptake in C2C12 cells.Conclusion A series of meroterpenoid-triterpenoid hybrids might exist in Ganoderma lucidum,and compound 8 has the potential for ameliorating insulin resistance and might be an effective substance of Ganoderma lucidum for anti-diabetes.

关 键 词：赤芝 杂萜 杂聚体 糖尿病/胰岛素抵抗 

分 类 号：R93[医药卫生—生药学]