Antiplasmodial activity and cytochrome p450 mediated pharmacokinetic drug interactions of xylopic acid

Abstract

acid (XA), the major constituent of the fruit of Xylopia aethiopica has shown several pharmacological properties. Consequently, the fruit is being used in the preparation of food. Traditionally, the plant is used to treat several diseases and it has been formulated into a nasal drop despite the lack of information about its safety, food-drug interaction, and other pharmacokinetic properties. Therefore, this study investigated the antiplasmodial effect of XA on P. falciparum, and its effect on rat liver CYP enzymes in vivo and in vitro. To establish the effect of XA on P. falciparum, the parasite strain Dd2 was cultured and treated with XA. Pentobarbitone-induced sleeping time was used to investigate the effect of XA on rat liver enzymes. Inhibition or induction of some isoforms of CYP450, CYP 1A1/1A2, 1A2, 2B1/2B2, 3A4, 2D6 and 2C9 was investigated using microsomal fractions of rat liver. The in vitro inhibition of selected CYP (1A2, 3A4) was assessed by treating rat liver microsomes XA. Results obtained showed that Xylopic acid exhibited negligible antiplasmodial activity. The IC50 of XA > 20 μM. Xylopic acid induced CYP 1A1/1A2, 1A2, 2D6, 2C9, and inhibited CYP3A4, 2B1/2B2. The findings would help mitigate toxicity and therapeutic failure especially in cases of co-administration of medications with food containing XA, with metabolism altered by the latter