维药黑桑中1个新的桑根酮型二氢黄酮化合物及其胰岛素增敏活性

A new sanggenon-type flavanone from Morus nigra and its insulin-sensitizing activity

目的 研究黑桑Morus nigra茎枝中桑根酮型二氢黄酮化合物及其胰岛素增敏活性。方法 应用多种色谱技术并结合桑根酮型化合物的紫外吸收特征,对桑根酮型化合物进行分离纯化,结合波谱技术及理化性质进行结构鉴定;采用地塞米松诱导胰岛素抵抗3T3-L1脂肪细胞模型,采用GOD-POD法和ELISA法来检测细胞上清液中葡萄糖和脂联素的含量,考察化合物的体外胰岛素增敏活性;通过LanthaScreenTMTR-FRET过氧化物酶体增殖物激活受体γ (peroxisome proliferator-activated receptor γ,PPARγ)竞争性结合检测试剂盒检测分离得到的化合物与PPARγ的结合能力。结果 从黑桑茎枝90%乙醇提取部位中分离得到1个新的桑根酮型化合物,并鉴定其结构为(5a R,10a S)-1,3,8,10a-四羟基-4-(2-羟基-3-甲基-3-丁烯-1-基)-5a-(3-甲基-2-丁烯-1-基)-5a,10a-二氢-11H-苯并呋喃[3,2-b]色原酮-11-酮,命名为黑桑根酮O(nigragenon O),该化合物在10、30μmol/L能促进胰岛素抵抗模型细胞对葡萄糖的摄取和对脂联素的分泌;对PPARγ受体具有较强的结合活性,半数抑制浓度(half maximal inhibitory concentration,IC50)为5.1μmol/L。结论 黑桑根酮O为新化合物,具有明显的体外胰岛素增敏活性,是PPARγ潜在配体。

Objective To investigate sanggenon-type flavanones(STFs) from the stems of Morus nigra and the insulin sensitizing activity. Methods Guided by the UV absorbtion characteristics of STFs, the compound was isolated and purified by a combination of various column chromatographic methods. The structure was elucidated through extensive analysis of HRMS, NMR, UV, IR, CD data and so on. The insulin-sensitizing activities of the compounds were investigated using insulin-resistant 3T3-L1 adipocytes model induced by dexamethasone. The concentration of glucose and adiponectin in the culture supernatant was determined by GOD-POD assay and ELSA method, respectively. The competitive binding affinity toward PPARγ was evaluated using the LanthaScreenTM TR-FRET assay. Results A new STF(1) was obtained and identified, named as nigragenon O. Compound 1 decreased the glucose level and promoted adiponectin secretion in the model cells at the concentrations of 30 μmol/L and 10 μmol/L. It also exhibited potent binding affinity for PPARγ with an IC50 value of 5.1 μmol/L. Conclusion Compound 1 showed obvious in vitro insulin-sensitizing effect and displayed potent binding affinity for PPARγ, indicating its potential as a natural insulin-sensitizing agent.