Inhibitory Effects of Danshen components on CYP2C8 and CYP2J2.

Inhibitory Effects of Danshen components on CYP2C8 and CYP2J2. Chem Biol Interact. 2018 Jun 01;289:15-22 Authors: Xu MJ, Jiang LF, Wu T, Chu JH, Wei YD, Aa JY, Wang GJ, Hao HP, Ju WZ, Li P Abstract The use of Chinese herbal medicines and natural products has become increasingly popular in both China and Western societies as an alternative medicine for the treatment of diseases or as a health supplement. Danshen, the dried root of Salvia miltiorrhiza (Fam.Labiatae), which is rich in phenolic acids and tanshinones, is a widely used herbal medicine for the treatment of cardio-cerebrovascular diseases. The goal of this study was to examine the inhibitory effects of fifteen components derived from Danshen on CYP2C8 and CYP2J2, which are expressed both in human liver and cardiovascular systems. Recombinant CYP2C8 and CYP2J2 were used, and the mechanism, kinetics, and type of inhibition were determined. Taxol 6-hydroxylation and astemizole O-desmethyastemizole were determined as probe activities for CYP2C8 and CYP2J2, respectively. Metabolites formations were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results demonstrated that salvianolic acid A was a competitive inhibitor of CYP2C8 (Ki = 2.5 μM) and mixed-type inhibitor of CYP2J2 (Ki = 7.44 μM). Salvianolic acid C had moderate noncompetitive and mixed-type inhibitions on CYP2C8 (Ki = 4.82 μM) and CYP2J2 (Ki = 5.75 μM), respecti...
Source: Chemico-Biological Interactions - Category: Molecular Biology Authors: Tags: Chem Biol Interact Source Type: research