Background: Terminalia arjuna Wight & Arn. (Combretaceae) is a tree having an
extensive medicinal potential in cardiovascular disorders. T. arjuna bark extract has been reported to
play a significant role as a cardiac stimulant for its beneficial effects in angina. Herb - drug interactions
(HDI) are one of the most important clinical concerns in the concomitant consumption of herbs and
prescription drugs. Our study was to investigate the in vitro CYP2D inhibition potential of Terminalia
arjuna (T. arjuna) extracts in rat liver microsomes and to study the influence of aqueous bark extract
of T. arjuna on the oral pharmacokinetics and pharmacodynamics of metoprolol succinate in rats.
Methods: The CYP2D inhibition potential of herbal extracts of T. arjuna was investigated in rat liver microsomes.
Pharmacokinetic-pharmacodynamic interaction of aqueous extract of T. arjuna with metoprolol succinate was investigated
Results: The ethyl acetate, alcoholic & aqueous bark extracts of T. arjuna showed potent reversible non-competitive
inhibition CYP2D enzyme in rat liver microsomes with IC50 values less than 40 μg/mL. Arjunic acid, arjunetin and
arjungenin did not show significant inhibition of CYP2D enzyme in rat liver microsomes. Pharmacokinetic studies
showed that aqueous bark extract of T. arjuna led to a significant reduction (P < 0.05) in AUC0-24h and Cmax of
metoprolol succinate in rats, when co-administered. Pharmacodynamic studies reveal a significant reduction in therapeutic
activity of metoprolol succinate on co-administration with aqueous bark extract of T. arjuna.
Conclusion: Based on our in vitro and in vivo findings and until further clinical drug interaction experiments are
conducted, the co-administration of drugs, especially those primarily cleared via CYP2D catalyzed metabolism, with
T. arjuna extracts should be done with caution.