Zhang Hong, Zheng Dan, Ding Zhi-Jie, Lao Yuan-Zhi, Tan Hong-Sheng, Xu Hong-Xi
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P.R. China.
Engineering Research Centre of Shanghai Colleges for TCM New Drug Discovery, Shanghai, 201203, P.R. China.
Sci Rep. 2016 Oct 21;6:35789. doi: 10.1038/srep35789.
A UPLC-PDA-QTOFMS-guided isolation strategy was employed to screen and track potentially new compounds from Garcinia oblongifolia. As a result, two new prenylated xanthones, oblongixanthones D and E (1-2), six new prenylated benzoylphloroglucinol derivatives, oblongifolins V-Z (3-7) and oblongifolin AA (8), as well as a known compound oblongifolin L (9), were isolated from the EtOAc-soluble fraction of an acetone extract of the leaves of Garcinia oblongifolia guided by UPLC-PDA-QTOFMS analysis. The structures of the new compounds were elucidated by 1D- and 2D-NMR spectroscopic analysis and mass spectrometry. Experimental and calculated ECD spectra were used to determine the absolute configurations. The results of wound healing and transwell migration assay showed that oblongixanthones D (1), E (2), and oblongifolin L (9) have the ability to inhibit cancer cell migration in lower cytotoxic concentrations. Western blotting results showed that these compounds exhibited an anti-metastasis effect mainly through downregulating RAF protein levels. In addition, 2 and 9 could inhibit phospho-MEK and phospho-ERK at downstream. Moreover, 1, 2, and 9 could inhibit snail protein level, suggesting that they could regulate the EMT pathway.
采用超高效液相色谱-光电二极管阵列-四极杆飞行时间质谱引导的分离策略,从长圆叶藤黄中筛选和追踪潜在的新化合物。结果,在超高效液相色谱-光电二极管阵列-四极杆飞行时间质谱分析的引导下,从长圆叶藤黄叶丙酮提取物的乙酸乙酯可溶部分中分离出两种新的异戊烯基黄酮,长圆叶黄酮D和E(1-2),六种新的异戊烯基苯甲酰基间苯三酚衍生物,长圆叶酚V-Z(3-7)和长圆叶酚AA(8),以及一种已知化合物长圆叶酚L(9)。通过一维和二维核磁共振光谱分析和质谱对新化合物的结构进行了阐明。利用实验和计算的电子圆二色谱确定绝对构型。伤口愈合和Transwell迁移试验结果表明,长圆叶黄酮D(1)、E(2)和长圆叶酚L(9)在较低细胞毒性浓度下具有抑制癌细胞迁移的能力。蛋白质免疫印迹结果表明,这些化合物主要通过下调RAF蛋白水平发挥抗转移作用。此外,2和9可在下游抑制磷酸化MEK和磷酸化ERK。而且,1、2和9可抑制蜗牛蛋白水平,表明它们可调节上皮-间质转化途径。