Dehmlow C, Murawski N, de Groot H
Institut für Physiologische Chemie, Universitätsklinikum, Essen, Germany.
Life Sci. 1996;58(18):1591-600. doi: 10.1016/0024-3205(96)00134-8.
The effects of the flavonoid silibinin, which is used for the treatment of liver diseases, on the formation of reactive oxygen species and eicosanoids by human platelets, white blood and endothelial cells were studied. Silibinin proved to be a strong scavenger of HOCI (IC50 7 microM), but not of O2- (IC50 > 200 microM) produced by human granulocytes. The formation of leukotrienes via the 5-lipoxygenase pathway was strongly inhibited. In human granulocytes IC50-values of 15 microM and 14.5 microM silibinin were detected for LTB4 and LTC4/D4/E4/F4 formation, respectively. In contrast to this, three- to fourfold silibinin concentrations were necessary to half maximally inhibit the cyclooxygenase pathway. For PGE2 formation by human monocytes an IC50-value of 45 microM silibinin was found. IC50-values of 69 microM and 52 microM silibinin were determined for the inhibition of TXB2 formation by human thrombocytes and of 6-K-PGF1 alpha formation by human omentum endothelial cells, respectively. Thus, the deleterious effects of HOCI that can lead to cell death, and those of leukotrienes that are especially important in inflammatory reactions, can be inhibited by silibinin in concentrations that are reached in vivo after the usual clinical dose. Silibinin is thought not only to display hepatoprotective properties but might also be cytoprotective in other organs and tissues.
研究了用于治疗肝病的类黄酮水飞蓟宾对人血小板、白细胞和内皮细胞中活性氧和类二十烷酸形成的影响。水飞蓟宾被证明是次氯酸（IC50为7微摩尔）的强清除剂，但不是人粒细胞产生的超氧阴离子（IC50>200微摩尔）的清除剂。通过5-脂氧合酶途径的白三烯形成受到强烈抑制。在人粒细胞中，检测到水飞蓟宾对LTB4和LTC4/D4/E4/F4形成的IC50值分别为15微摩尔和14.5微摩尔。与此相反，抑制环氧化酶途径的半数最大效应需要水飞蓟宾浓度提高三到四倍。对于人单核细胞形成PGE2，发现水飞蓟宾的IC50值为45微摩尔。水飞蓟宾对人血小板TXB2形成的抑制和对人网膜内皮细胞6-K-PGF1α形成的抑制的IC50值分别测定为69微摩尔和52微摩尔。因此，水飞蓟宾可以抑制次氯酸可能导致细胞死亡的有害作用以及白三烯在炎症反应中特别重要的有害作用，其浓度在通常临床剂量后在体内即可达到。水飞蓟宾不仅被认为具有肝脏保护特性，而且在其他器官和组织中可能也具有细胞保护作用。
