Thesis (M.Sc. In Pharm)--Chulalongkorn University, 2007

The paraoxonases (PONs) family consists of three members, PON1, PON2, and PON3. PON1 and PON3 are expressed primarily in the liver and excreted in the blood by associated with high density lipoprotein (HDL) while PON2 expressed widely in a number of tissues and cells and undetectable in HDL and low density lipoprotein (LDL). PONs have been shown to reduce the oxidation of LDL and HDL, thus possibly protecting against atherosclerosis. Activity of PONs is modulated by various factors including hypolipidemic agents. Curcuma comosa Roxb. (Zingiberaceae) is an indigenous plant of Thailand and has been widely used in Thai traditional medicine for treatment of abnormal uterine symptoms. Recently, hypolipidemic effect and antioxidant effect of C. comosa were extensively investigated. The purpose of this study was to investigate effects of C. comosa on PONs activities and oxidative stress in rabbits fed with high-cholesterol diet. Twelve male New Zealand White (NZW) rabbits were randomly divided into three treatment groups of 4 rabbits each. All treatment groups were treated with 1.0% cholesterol for 1 month and subsequently treated with either 0.5% cholesterol or 0.5% cholesterol combined simvastatin at the dosage of 5 mg/day or 0.5% cholesterol combined C. comosa at the dosage of 400 mg/kg/day for 3 months. At 4 months after treatment, blood as well as abdominal aorta were collected from all rabbits for determination of lipid parameters, PONs activities and oxidative stress parameters. The results showed that C. comosa significantly decreased levels of total cholesterol and LDL similarly to simvastatin. In addition, C. comosa significantly increased oxidative stress similarly to simvastatin. We found that both C. comosa and simvastatin did not affect PONs activities. Thus, long term treatment of C. comosa exhibited hypolipidemic effect and increased oxidative stress similarly to simvastatin but did not affect PONs activities.