Abstract Previous studies have shown that Portulica Oleraceaeethanolic extractcan significantly modulate the activity of several drug metabolizing enzymes, this may affect the bioavailability of drugs resulting in over dose or less therapeutic effects. This study was designed to assess the inhibitory effects of cisplatin (CDDP) and paclitaxel (PAX) on two types of CYP450 isoformers namely: CYP2E1 and CYP3A1/2 in hepatic microsomes isolated from normal and Portulica Oleraceae pretreated rats. CDDP and PAX were used by different concentrations to hepatic microsomes isolated from normal and Portulica Oleraceae (250 mg/kg/day) pretreated rats for 10 days after receiving pyrazole or dexamethasone for induction of CYP2E1 and CYP3A1/2 respectively. Addition of CDDP or PAX by (10, 50 and 100 μM) to hepatic microsomes from normal or Portulica Oleraceae pretreated rats caused a concentration dependent inhibition of CYP2E1, with an evidence of less inhibition in Portulica Oleraceae pretreated microsomes particularly at higher concentration. Cisplatin (CDDP) (10, 50 and 100 μM) caused a concentration dependant inhibition of CYP3A1/2 that was enhanced by Portulica Oleraceae pretreatment. The inhibitory influence of PAX (10, 50 and 100 μM) on CYP3A1/2 decreased with increasing the drug concentration and this inhibition was augmented by Portulica Oleraceae pretreatment. PAX has an inhibitory effect on 2E1 and 3A1/2 isozymesmore than CDDP. Pretreatment with Portulica Oleraceae decreased an inhibition in 2E1, while the inhibition was enhanced by 3A1/2. In conclusion, Portulica Oleraceae pretreatment attenuated the inhibitory influence of cisplatin (CDDP) and paclitaxel (PAX) on CYP2E1 activity and magnified their inhibition on CYP3A1/2. Thus, use of Portulica Oleraceae ethanolic extract with drugs should raise concern for drugs–herb interactions.
Keywords Portulica Oleraceae, Cisplatin, Paclitaxel, CYP 2E1, CYP 3A1/2 isoenzymes.