Scavenging of reactive oxygen species and inhibition of arachidonic acid metabolism by silibinin in human cells

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 HOCl (IC50 7 mu M), but not of O-2(-) (IC50>200 mu M) produced by human granulocytes. The formation of leukotrienes via the 5-lipoxygenase pathway was strongly inhibited. In human granulocytes IC50-values of 15 mu M and 14.5 mu M silibinin were detected for LTB(4) and LTC(4)/D-4/E(4)/F-4 formation, respectively. In contrast to this, three- to fourfold silibinin concentrations were necessary to halfmaximally inhibit the cyclooxygenase pathway. For PGE(2) formation by human monocytes an IC50-value of 45 mu M silibinin was found. IC50-values of 69 mu M and 52 mu M silibinin were determined for the inhibition of TXB(2) formation by human thrombocytes and of 6-K-PGF(1 alpha) formation by human omentum endothelial cells, respectively. Thus, the deleterious effects of HOCl 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.