Subchronic exposure of Pueraria mirifica in normal - and high cholesterol diet fed rats : influence on hepatic cytochrome P450, lipid profile and toxicity

Abstract

Pueraria mirifica airy shaw and suvatabandhu, know locally as Kwao Keur, is a plant in family Leguminosae. In this study, effects of P.mirifica on hepatic cytochrome P450 (CYP), serum lipid profile and subchronic toxicity were investigated in male Wistar rats. Rats were randomly divided into four treatment groups as following: normal diet-fed group; normal diet-fed supplemented with P.mirifica group; high cholesterol diet-fed group; high cholesterol diet-fed supplemented with P.mirifica group. Each group comprised 10 rats. P.mirifica was administered orally at a dosage of 100 mg/kg/day for 90 consecutive days. At the end of the treatment, animals were anesthesized. Blood samples were collected by heart puncture and serum sample were prepared for determination of hematology and clinical blood chemistry, respectively. Microsomes were prepared from livers for enzyme assays. The results showed that body weight of rats given P.mirifica in either normal diet or high cholesterol diet conditions were significantly lower than their corresponding control groups. There was no significant difference of these following hematology and clinical blood chemistry: hemoglobin, hemotocrit, WBC count, %differential WBC, platelet count, RBC morphology, glucose, BUN, SCr, total bilirubin, and direct bilirubin in all experimental groups. P.mirifica did not affect serum level of AST, ALT, and ALP in normal diet-fed condition. High cholesterol diet-fed condition caused a significant increase of AST, ALT, and ALP but P.mirifica attenuated these effects. P.mirifica significantly decreased serum total cholesterol and LDL-C in either normal diet-fed or high cholesterol diet-fed rats. Serum triglyceride was increased in normal diet-fed rats but decreased in high cholesterol diet-fed rats. P.mirifica caused a significant decrease of HDL-C in both normal and high cholesterol diet-fed rats whereas its improvement in the LDL-C/HDL-C ratio was shown only in high cholesterol diet-fed rats. Concerning the effects on CYPs, P.mirifica significantly inhibited CYP2B1&B2 in either normal diet or high cholesterol diet-fed rats. Its inhibitory effect of CYP1A2 and CYP2E1 was found only in normal diet-fed rats. No effect of P.mirifica was found on CYP1A1 and CYP3A. Inhibitory effects of P.mirifica on CYP2B1&2B2 and CYP2E1 were also found in the in vitro study. Although, P.mirifica demonstrated a benefit on lipid profile and did not show any toxic effects on liver, kidney, and blood system in this study, an increment of serum triglyceride in normal rat receiving P.mirifica, howerer, is not favorable. Inhibitory effects of P.mirifica on CYP1A2, CYP2B1&2B2 and CYP2E1 indicated a beneficial potential of this plant regarding the chemical-induced carcinogenesis as well as a possible potential of this plant regarding drug-drug interaction with other medicines that are metabolized by these CYPs. Effects of P.mirifica at various doses, long term used as well as mechanism of effects should be further investigated. Effects of P.mirifica on other isoforms of CYP in human should also be explored.