Alizarin strongly inhibits P450 isoform CYP1A1, CYP1A2 and CYP1B1 with IC50 of 6.2/10.0 and 2.7 μM respectively, weakly inhibits CYP2A6 and CYP2E1, and does not inhibit CYP2C19, CYP3A4 and CYP3A5.
Among human P450s, CYP1A1, CYP1A2, CYP1B1 and CYP3A4 are involved in bioactivation of carcinogens such as heterocyclic amines and polycyclic aromatic compounds. CYP1A2 is expressed constitutively in hepatic tissues where most carcinogens are metabolized. CYP1A1 is induced on treatment with Ah-receptor binding agents. CYP1B1 is widely distributed in human extrahepatic tissues, and it is constitutively expressed and is inducible by Ah-receptor ligands[4]. Alizarin strongly inhibits the activities of CYP1A1, CYP1A2 and CYP1B1, with IC50 values of 6.2 μM, 10.0 μM and 2.7 μM, respectively, and weakly suppresses those of CYP2A6 and CYP2E1 in a dose-dependent manner, but do not inhibit those of CYP2C19, CYP3A4 and CYP3A5. CYP1B1 is the most strongly affected cytochrome P450 (CYP) molecule in a competitive manner by alizarin among CYPs examined in the study. The Km value of CYP1B1 is 11 μM, and the Ki value of alizarin against CYP1B1 is 0.5 μM[4]. Alizarin suppressed the mutagenicity of MeIQx in TA1538 1A2/OR or 1B1/OR, which suggested that the antigenotoxic activities of alizarin can be explained by inhibition of CYP activities responsible for activating the mutagens[4]. Alizarin was a very good antioxidant in their activity against iodophenol-derived phenoxyl radicals, superoxide anion radicals and lipid peroxidation in rat liver microsomes. In vivo experiment showed that alizarin reduced the hepatic content of thiobarbituric acid-reactive substances and lowered the serum level of alanine aminotransferase in poisoned animals [3].
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