hesis (M.Sc. in Pharm)--Chulalongkorn University, 2002

Boraphet (Tinospora crispa Miers ex Hook. f. & Thomson) has been used traditionally as hypoglycemic medicine. In this study, subacute effects of T. crispa stem extract on hepatic cytochrome P450 (CYPs) and clinical blood chemistry were investigated in male Wistar rats. Rats were randomly divided into three treatment groups as following: Control group, T. crispa treatment group I and II, the groups of which rats received T. crispa at doses of 250 and 500 mg/kg/day, respectively. Each group consisted of 10 rats. T. crispa was administered orally for 30 consecutive days. At the end of the treatment, animals were anesthetized. Blood samples were collected by heart puncture and serum samples were determined for clinical blood chemistry. Microsomes were prepared from livers and being used for enzyme activity assays. The results showed that T. crispa at both dosages given in this study did not affect body weight, relative liver weight as well as the following clinical blood chemistry: Total cholesterol, triglyceride, AST, ALT, ALP, total bilirubin, direct bilirubin, BUN, SCr, sodium, chloride, hemoglobin, hematocrit, RBC morphology, platelet count, WBC count, and %differential WBC. Rats receiving T. crispa at 250 and 500 mg/kg/day possessed significantly lower serum potassium than those in the control group. Rats receiving T. crispa of 500 mg/kg/day possessed significantly lower serum glucose but significantly higher serum HDL-C levels as compared to the control group. Regarding the effects on CYPs, T. crispa at both doses caused significantly decrease of total CYP contents. Determining activities of individual CYP isoform, it was found that T. crispa at 500 mg/kg/day caused inhibition effect on CYP1A1 but induction effect on CYP2E1. T. crispa at both dosages did not affect activities of CYP1A2, CYP2B1&2B2, and CYP3A. These provided a preliminary data indicating that high dose of T. crispa may increase and decrease risk of chemical carcinogenesis and/or mutagenesis via its modulating effects on the bioactivating enzymes, CYP1A1 and CYP2E1.