Hsiao Sui-Wen, Wu Yu-Chin, Mei Hui-Ching, Chen Yu-Hsin, Hsiao George, Lee Ching-Kuo
Ph.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, 250 Wu Xin Street, Taipei 11031, Taiwan.
Graduate Institute of Pharmacognosy, Taipei Medical University, 250 Wu Xin Street, Taipei 11031, Taiwan.
Molecules. 2021 Apr 26;26(9):2537. doi: 10.3390/molecules26092537.
In this novel study, we isolated 28 compounds from the leaves of (Lour.) Gilg based on a bioassay-guided procedure and also discovered the possible matrix metalloprotease 2 (MMP-2) and 9 (MMP-9) modulatory effect of pheophorbide A (PA). To evaluate the regulatory activity on MMP-2 and MMP-9, the HT-1080 human fibrosarcoma cells were treated with various concentrations of extracted materials and isolated compounds. PA was extracted by methanol from the leaves of and separated from the fraction of the partitioned ethyl acetate layer. PA is believed to be an active component for MMP expression since it exhibited significant stimulation on MMP-2 and proMMP-9 activity. When treating with 50 μM of PA, the expression of MMP-2 and MMP-9 were increased 1.9-fold and 2.3-fold, respectively. PA also exhibited no cytotoxicity against HT-1080 cells when the cell viability was monitored. Furthermore, no significant MMP activity was observed when five PA analogues were evaluated. This study is the first to demonstrate that C-17 of PA is the deciding factor in determining the bioactivity of the compound. The MMP-2 and proMMP-9 modulatory activity of PA indicate its potential applications for reducing scar formation and comparative medical purposes.
在这项新颖的研究中，我们基于生物测定引导的程序从（Lour.）Gilg的叶子中分离出28种化合物，并且还发现了脱镁叶绿酸A（PA）对基质金属蛋白酶2（MMP - 2）和9（MMP - 9）可能的调节作用。为了评估对MMP - 2和MMP - 9的调节活性，用不同浓度的提取物和分离出的化合物处理HT - 1080人纤维肉瘤细胞。PA通过甲醇从（Lour.）Gilg的叶子中提取，并从分配的乙酸乙酯层的馏分中分离出来。PA被认为是MMP表达的活性成分，因为它对MMP - 2和前MMP - 9活性表现出显著的刺激作用。当用50μM的PA处理时，MMP - 2和MMP - 9的表达分别增加了1.9倍和2.3倍。在监测细胞活力时，PA对HT - 1080细胞也没有细胞毒性。此外，在评估五种PA类似物时未观察到明显的MMP活性。这项研究首次证明PA的C - 17是决定该化合物生物活性的决定性因素。PA对MMP - 2和前MMP - 9的调节活性表明其在减少瘢痕形成和比较医学目的方面的潜在应用。
