Xu Guang-Hua, Kim Young-Hee, Choo Soo-Jin, Ryoo In-Ja, Yoo Jae-Kuk, Ahn Jong-Seog, Yoo Ick-Dong
Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea.
Arch Pharm Res. 2009 Sep;32(9):1215-20. doi: 10.1007/s12272-009-1905-7. Epub 2009 Sep 26.
Human neutrophil elastase (HNE), a serine protease with broad target specificity, is the only enzyme responsible for the degradation of elastin which is an insoluble elastic fibrous protein in animal connective tissue. Biologically, elastase activity significantly increased with age, which results in a reduced skin elasticity and in the appearance of wrinkles or stretchmarks. In the course of our screening program for HNE inhibitors from natural source, the MeOH extract of Ilex paraguariensis leaves showed strong HNE inhibitory effect. Bioassay-guided fractionation led to the isolation of a new pyrrole alkaloid (1), along with seventeen known compounds (2-18) from the MeOH extract of Ilex paraguariensis leaves, and their chemical structures were elucidated on the basis of spectroscopic analysis. All isolated compounds were evaluated for HNE inhibitory activity, and the result demonstrated that dicaffeoylquinic acid derivatives (12, 13, 14, 15 and 16) and flavonoids (8 and 17) exhibited potent HNE inhibitory activity with IC50 values ranging from 1.4 to 7.3 microM.
人中性粒细胞弹性蛋白酶（HNE）是一种具有广泛底物特异性的丝氨酸蛋白酶，是动物结缔组织中负责降解弹性蛋白（一种不溶性弹性纤维蛋白）的唯一酶。从生物学角度来看，弹性蛋白酶活性会随着年龄的增长而显著增加，这会导致皮肤弹性降低，并出现皱纹或妊娠纹。在我们从天然来源筛选HNE抑制剂的过程中，巴拉圭冬青叶的甲醇提取物显示出很强的HNE抑制作用。通过生物测定导向的分级分离，从巴拉圭冬青叶的甲醇提取物中分离出一种新的吡咯生物碱（1）以及十七种已知化合物（2 - 18），并根据光谱分析阐明了它们的化学结构。对所有分离出的化合物进行了HNE抑制活性评估，结果表明二咖啡酰奎尼酸衍生物（12、13、14、15和16）和黄酮类化合物（8和17）表现出较强的HNE抑制活性，IC50值在1.4至7.3微摩尔范围内。
