Bioactivity guided fractionation of methanolic extract of Terminalia arjuna for its CYP3A and CYP2D inhibition in rat liver microsomes.

Abstract

Terminalia arjuna (T. arjuna) is an Indian medicinal plant belonging to the family Combretaceae and possesses numerous therapeutic activities including its immense cardioprotective activity. In the present work, a methanolic bark extract of T. arjuna was evaluated for CYP3A and CYP2D inhibition potential in rat liver microsomes (RLM). Further, the methanolic bark extract was fractionated successively using increasing polarity solvents starting with petroleum ether, chloroform, ethyl acetate and n-butanol. The fractions so obtained were also evaluated for their CYP3A and CYP2D inhibition potential. Probe substrates testosterone and dextromethorphan were used for CYP3A and CYP2D respectively. The IC50 values for the methanolic extract and the fractions were found to be less than 50μg/ml in RLM for both CYP3A and CYP2D isoenzymes. The most potent n-butanol fraction was further fractionated with column chromatography to isolate the highest active constituent responsible for the activity. Fraction 4 of the n-butanol extract was the most potent fraction with IC50 values of 5.64 ± 0.735μg/ml and 16.63 ± 0.879μg/ml for CYP3A and CYP2D in RLM, respectively. Therefore, in vitro data indicated that the Terminalia arjuna extract contains constituents that can potentially inhibit the CYP3A and CYP2D isoenzymes which may in turn lead to pharmacokinetic drug-herb interaction.