Division of Convergence on Marine Science, Korea Maritime and Ocean University, Busan 49112, Korea.
Department of Food and Nutrition, Silla University, Busan 46958, Korea.
Int J Mol Sci. 2022 Feb 28;23(5):2660. doi: 10.3390/ijms23052660.
A phenyl ethanoid, salidroside (SAL), and two secoiridoids, 8()-nuezhenide (NZD) and ligustroside (LIG), were isolated from fruits of used as traditional folk medicine, and their chemical structures were elucidated by the comparison of spectral data with published literature. Matrix metalloproteinases (MMPs) are major enzymes that play crucial roles in the metastasis and invasive behavior of tumors. In particular, MMP-2 and MMP-9, regulated by the MAPK signaling pathways, including p38, ERK and JNK, are known to play a key role in the degradation of the basement membrane. In the present study, the effects of SAL, NZD and LIG on the expression of MMP-2 and -9 were examined in phorbol 12-myristate 13-acetate (PMA)-induced HT 1080 cells. All the compounds significantly lowered the amount of MMP-2 and MMP-9 released, as determined by gelatin zymography and ELISA. In addition, the mRNA and protein expression levels of MMP-2 and MMP-9 were significantly suppressed, as measured by RT-PCR and Western blotting. According to the Western blotting assay, SAL and LIG effectively reduced the expression of MMP-2 in a dose-dependent manner. NZD lowered the expression of MMP-9 in a similar way. The phosphorylation of p38, ERK and JNK was also significantly suppressed by these compounds. These findings suggest that all the compounds regulate the release and expression of MMP-2 and MMP-9 via MAPK signaling pathways.
从 用作传统民间药物的果实中分离得到苯乙醇苷、红景天苷（SAL）和两种裂环环烯醚萜苷，8()-牛儿醇苷（NZD）和毛蕊花糖苷（LIG），并通过与文献报道的光谱数据比较阐明了它们的化学结构。基质金属蛋白酶（MMPs）是在肿瘤转移和侵袭行为中起关键作用的主要酶。特别是 MMP-2 和 MMP-9，受 MAPK 信号通路（包括 p38、ERK 和 JNK）调节，已知在基底膜的降解中起关键作用。在本研究中，研究了 SAL、NZD 和 LIG 对佛波醇 12-肉豆蔻酸 13-乙酸酯（PMA）诱导的 HT 1080 细胞中 MMP-2 和 MMP-9 表达的影响。所有化合物通过明胶酶谱和 ELISA 均显著降低 MMP-2 和 MMP-9 的释放量。此外，通过 RT-PCR 和 Western blot 测定，MMP-2 和 MMP-9 的 mRNA 和蛋白表达水平也明显受到抑制。根据 Western blot 分析，SAL 和 LIG 可有效剂量依赖性地降低 MMP-2 的表达。NZD 以类似的方式降低 MMP-9 的表达。这些化合物还显著抑制了 p38、ERK 和 JNK 的磷酸化。这些发现表明，所有化合物均通过 MAPK 信号通路调节 MMP-2 和 MMP-9 的释放和表达。
