Subacute effects of Orthosiphon Grandiflorus aqueous extract on Hepatic Cytochrome P450 and Clinical blood chemistry in rats

Abstract

Orthosiphon grandiflorus Bold, is commonly called in Thai as “Yaa nuat maeo”. O. grandiflorus has been used traditionally as a diuretic and treatment of urinary stone disease. This study examined subacute effects of o. grandiflorus aqueous extract on phase I hepatic cytochrome P450 (CYP) in rats. In addition, effects of this plant extract on clinical blood chemistry and hematology were also determined. Thirty male Wistar rats were randomly divided into three treatment groups, of ten rats in each group. Rats in the first group were given distilled water 1 ml/kg/day serving as a control group. The other two groups of rats were given O. grandiflorus aqueous extract at dosages of 0.96 and 4.8 g/kg/day. Test compounds were administered orally for 30 consecutive days. During the treatment period, body weight was recorded every week. At the end of the treatment period, rats were anesthesized. Blood samples were collected by heart puncture and serum samples were prepared for measuring hematology and clinical blood chemistry, respectively. Microsomes were prepared from livers and used for determining of total CYP contents as well as activities of CYP1A1, 1A2, 2B1/2, 2E1 and 3A. The results showed that body weight gain of rats given o. grandiflorus aqueous extract at 4.8 g/kg/day was significantly lower than those in the control group. No significant effects of o. grandiflorus were shown on relative liver weight as well as these following clinical blood chemistry and hematology: hematocrit, hemoglobin, platelet count, white blood cell count, red blood cell count, RBC indices (MCV, MCH and MCHC), RBC morphology, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, direct bilirubin, serum creatinine, total cholesterol, triglyceride, low density lipoprotein-cholesterol, high density lipoprotein-cholesterol, glucose, uric acid and electrolytes (such as sodium, chloride and calcium), O. grandiflorus aqueous extract at the dose of 4.8 g/kg/day caused a significant increase of blood urea nitrogen and serum potassium. Both dosages of O. grandiflorus aqueous extract did not affect the activities of CYP1A1, 1A2, 2B1/2, 2E1 and 3A. However, a significant decrease of total CYP content was found in rats receiving o. grandiflorus at 4.8 g/kg/day. Further study was suggested to find out which individual CYP isoform was affected by o. grandiflorus administration. In conclusion, results from this study provided a preliminary information that drug-drug interaction and potential of increase/decrease of xenobiotic-induced toxicity, mutagenesis and/or carcinogenesis would not be expected by O. grandiflorus administration if this plant aqueous extract was given concomitantly with drugs or with an exposure of xenobiotics that were metabolized/bioactivated by the CYP isoforms investigated in this study.