Antiplasmodial Activity And Cytochrome P450 Mediated Pharmacokinetic Drug Interactions Of Xylopic Acid

ABSTRACT

Xylopic 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.