Subacute effects of Morinda citrifolia fruit extract on hepatic cytochrome P450 and clinical blood chemistry in rats

Abstract

Morinda citrifolia Linn., called in Thai as “Yor” has been reported to have a broad range of therapeutic effects. This study examined subacute effects of M. citrifolia fruit extract on phase l hepatic cytochrome P450 (CYP) involving carcinogenic/mutagenic bioactivation such as CYP1A1, CYP1A2, CYP2B1/2B2, CYP2E1 and CYP3A in rats. Effects of this compound on clinical blood chemistry and hematology were also determined. Thirty male Wistar rats were randomly divided into 3 treatment groups. Each group comprised 10 rats. Rats in the first group were given distilled water 1 ml/kg/day orally for 30 days, serving as a control group. The other two groups of rats were given M. citrifolia fruit extract orally at dosages of 600 and 1200 mg/kg/day for 30 days. During the treatment period, body weight, food consumption and volume of drinking water were recorded at every five days. At the end of the treatment period, rats were anesthesized. Blood was collected by heart puncture and serum was prepared for measuring hematology and clinical blood chemistry, respectively. Microsomes were prepared from livers for enzyme assays. The results showed that there were no significant differences between control and treatment groups on body weight, food & water consumption. M. citrifolia significantly decreased CYP1A1 activity at a dosage of 1200 mg/kg/day but not at a dosage of 600 mg/kg/day. No changes of CYP1A2, CYP2B1/2B2, CYP2E1 and CYP3A activities were observed following both doses of the extract. The inhibitory effect of M. citrifolia fruit extract at 1200 mg/kg/day on CYP1A1 may partly explain its antimutagenic/anticarcinogenic effects of this plant on chemical-induced mutagenesis/carcinogenesis previously reported by other investigators. For clinical blood chemistry, rats received both dosage regimens of M. citrifolia demonstrated no changes of the following clinical blood chemistry and hematology : SGOT, SGPT, ALP, total bilirubin, direct bilirubin, BUN, SCr, total cholesterol, TG, HDL-C, glucose, sodium, potassium, chloride, hemoglobin, hematocrit, platelet count, WBC count, % differential WBCs and RBC morphology. This result illustrated that M. citrifolia fruit extract did not modulate activities of most of the phase l bioactivating enzymes except for CYP1A1 following high dose of the extract. In addition, no effect of this extract was shown on several important organs/systems such as liver, kidney, blood system, electrolytes as well as lipid and carbohydrate metabolish. Further studies to clarify the inhibition effects of M. citrifolia fruit extract on CYP1A1 were suggested.