Effects of subchronic exposure of Pueraria Mirifica on hepatic cytochrome P450 and blood clinical biochemistry parameters in rats

Abstract

Pueraria mirifica Airy Shaw and Suvatabandhu, known locally as Kwao Keur, is considered to be a rejuvenating folk medicine. In this study, the subchronic effects of P.mirifica on hepatic cytochrome P450 (CYP) and blood clinical biochemistry parameters 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 consisted of 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 determined for clinical biochemistry parameters. 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 blood clinical biochemistry parameters: hemoglobin, hematocrit, 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.mirfica helped attenuate 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&2B2 in either normal diet or high cholesterol diet-fed rats. Its inhibition effect of CYP1A2 and CYP2E1 was found only in normal diet-fed rats. No effect of P.mirifica was found on CYP1A1. Inhibition effects of P.mirifica on CYP2B1&2B2 and CYP2E1 were also found in the 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, however, is not favorable. Inhibition effects of P.mirifica on CYP1A2, CYP2B1&2B2 and CYP2E1 indicated a beneficial potential of the compound on chemical-induced carcinogens via these enzymes. Effects of P.mirifica at various doses, long term used as well as mechanism of effects should be further investigated. Effects of this compound on other isoforms of CYP should also be explored.