Cho J Y, Park J, Yoo E S, Baik K U, Jung J H, Lee J, Park M H
Department of Inflammation, Allergy and Autoimmune Diseases, Daewoong Pharmaceutical Co. Ltd., Sungnam, Korea.
Planta Med. 1998 Oct;64(7):594-7. doi: 10.1055/s-2006-957528.
Total methanol extract of Saussurea lappa radix (Compositae) showed potent inhibitory effect on the production of tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, in murine macrophage-like cell (RAW264.7 cells) in our previous screening studies on 120 Korean medicinal plants. The activity-guided purification of the plant resulted in the isolation of three components. The chemical structures of the components isolated were established by spectroscopic analyses as sesquiterpene lactones [cynaropicrin (1), reynosin (2), and santamarine (3)]. These three compounds inhibited TNF-alpha production in a dose-dependent manner. The molar concentrations of cynaropicrin, reynosin, and santamarine producing 50% inhibition (IC50) of TNF-alpha production were 2.86 micrograms/ml (8.24 microM), 21.7 micrograms/ml (87.4 microM), and 26.2 micrograms/ml (105 microM), respectively. However, treatment with sulphydryl (SH) compounds such as L-cysteine, dithiothreitol, and 2-mercaptoethanol abrogated the inhibitory effect of cynaropicrin on TNF-alpha production. Therefore, we conclude that the principal inhibitory component of Saussurea lappa is cynaropicrin and its inhibitory effect is mediated through conjugation with SH-groups of target proteins.
在我们对120种韩国药用植物进行的前期筛选研究中，木香（菊科）的总甲醇提取物对小鼠巨噬细胞样细胞（RAW264.7细胞）中促炎细胞因子肿瘤坏死因子-α（TNF-α）的产生显示出强效抑制作用。对该植物进行活性导向纯化后分离出三种成分。通过光谱分析确定所分离成分的化学结构为倍半萜内酯[菜蓟苦素（1）、雷诺辛（2）和异土木香内酯（3）]。这三种化合物以剂量依赖性方式抑制TNF-α的产生。菜蓟苦素、雷诺辛和异土木香内酯产生50% TNF-α产生抑制率（IC50）的摩尔浓度分别为2.86微克/毫升（8.24微摩尔）、21.7微克/毫升（87.4微摩尔）和26.2微克/毫升（105微摩尔）。然而，用巯基（SH）化合物如L-半胱氨酸、二硫苏糖醇和2-巯基乙醇处理可消除菜蓟苦素对TNF-α产生的抑制作用。因此，我们得出结论，木香的主要抑制成分是菜蓟苦素，其抑制作用是通过与靶蛋白的SH基团结合介导的。
