关键词: Cordia dichotoma ECD GLUT4 translocation dichotomins A-K

Mesh : Glucose Transporter Type 4 / metabolism genetics Fruit / chemistry Glucose / metabolism Phenols / chemistry pharmacology metabolism Animals Rats Plant Extracts / chemistry pharmacology metabolism Biological Transport / drug effects Molecular Structure Cell Line Protein Transport Humans AMP-Activated Protein Kinases / metabolism chemistry

来  源:   DOI:10.1021/acs.jafc.4c02672

Abstract:
From the fruits of Cordia dichotoma, 11 new phenolic compounds, dichotomins A-K, were isolated, together with 19 known compounds. Through the analysis of detailed NMR data and HRESIMS data, the planar structures of all compounds were confirmed. Using NMR calculations, the absolute configuration of dichotomins A-K was elucidated by comparing their observed and computed electronic circular dichroism (ECD) spectra. Dichotomin H (8) and dichotomin I (9) were determined as two pairs of enantiomers. The enantiomers of compounds 8 and 9 were separated using chiral-phase high-performance liquid chromatography (HPLC), and the stereostructure of each enantiomer was determined by similarly calculating the ECD. Compounds 3, 5, 7, 17, 18, 23-25, and 27-30 increased glucose uptake by 1.04- to 2.85-folds at concentrations of 30 μg/mL. Further studies revealed that compounds 3 and 5 had a moderate effect on glucose transporter 4 (GLUT4) translocation activity in L6 cells. At 30 μg/mL, compound 3 significantly enhanced AMPK phosphorylation and GLUT4 expression. As a whole, compound 3 has the potential to be a drug candidate for the treatment of type 2 diabetes mellitus (T2DM).
摘要:
从科迪亚的果实中,11个新的酚类化合物,二分法A-K,被隔离,连同19种已知化合物。通过详细的NMR数据和HRESIMS数据的分析,证实了所有化合物的平面结构。使用NMR计算,通过比较观察到的和计算的电子圆二色性(ECD)光谱,阐明了二分法A-K的绝对构型。将双光菌素H(8)和双光菌素I(9)确定为两对对映异构体。化合物8和9的对映体采用手性相高效液相色谱(HPLC)分离,并且通过类似地计算ECD来确定每个对映异构体的立体结构。化合物3、5、7、17、18、23-25和27-30在30μg/mL的浓度下使葡萄糖摄取增加1.04-至2.85倍。进一步的研究表明,化合物3和5对L6细胞中的葡萄糖转运蛋白4(GLUT4)易位活性具有中等作用。在30μg/mL时,化合物3显著增强AMPK磷酸化和GLUT4表达。作为一个整体,化合物3有可能成为治疗2型糖尿病(T2DM)的候选药物。
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