The present study was carried out to investigate the effects of oral administration of aqueous extract of Punicagranatum seed on Triton X-100 induced hypercholesterolemia in rats. Hypercholesterolemia was induced by single intraperitoneal injection of Triton X-100 and the rats were later treated with aqueous extract of Punicagranatum seed at different dosage levels (50,100 and 200mg/kg body weight) and 10ml/kg/day of standard drug (Astrovastatin) for seven days. Another group received 0.9% Normal saline (1 ml/kg/day). Animals were euthanized by anaesthetization at the end of the experiment to harvest serum used for the biochemical analysis. Aqueous extract of Punicagranatum seed extract prevented triton- induced increase in serum cholesterol, triglyceride (TG), low density lipoprotein (LDL) and decrease in high density lipoprotein (HDL) in a statistically significant manner (p < 0.05) and reversed the elevated serum LDL/HDL ratio comparably to Astrovastatin. The results demonstrated the amelioration of triton- induced hypercholesterolemia in rats by aqueous extract of Punicagranatum seed. Consequently, we can hypothesize that the part of Punicagranatum seed mediated therapeutic effects is associated with its antiatherogenic/hypolidemic component.

CHAPTER ONE: INTRODUCTION

1.1       BACKGROUND OF STUDY
Hypercholesterolemia is a lipoprotein metabolic disorder characterized by increase in plasma low density lipoprotein (LDL-c) and very low density lipoprotein (VLDL-c) cholesterols or decrease in plasma high density lipoprotein cholesterol (HDL-c). It was reported to be one of the most important risk factors in the development and progression of atherosclerosis that led to cardiovascular diseases (Rerkasem et al., 2008). Hypercholesterolemia poses a major problem to many societies as well as health professionals because of the close correlation between cardiovascular diseases and lipid abnormalities (Matos et al., 2005; Ramachandran et al., 2003). Hypercholesterolemia is highly prevalent in all the geopolitical zones of Nigeria. It ranges from 60% among apparently healthy Nigerians to 89% among diabetic Nigerians (Oguejiofor et al., 2012). Clinical trials have demonstrated that intensive reduction of plasma low density lipoprotein (LDL-c) levels could reverse atherosclerosis and decrease the incidence of cardiovascular diseases (Brown and Jessup, 1999; Ichihashi et al., 1998).
Punicagranatumcommonly known as pomegranate is a member of monogeneric family, punicacae and is mainly found in Iran which is considered to be its primary centre of origin (Facciola, 1990).Punicagranatum can be divided into several anatomical compartments including seed,juice,peal,leaf,flower,bark and root each possessing interesting pharmacological and toxicological activities. Punicagranatumhas extensively been used as a traditional remedy against acidosis,microbial infection,diarrhea (Kim and Choi, 2009).Punicagranatum seeds have also been shown to contain estrogenic compounds,oestrone and oestradiol (Kim and choi, 2009).The seeds are embedded in a white, spongy astringent pulp (Stover and Mercure, 2007). Punicagranatum is known for its high antioxidant capacity, it has been used for medicinal purposes for centuries (Syed et al 2007). Punica granatum products have also been reported to possess among others anti-inflammatory, antimicrobial and protective effects on liver function and lipid glucose metabolism (Medjakovic and jungbauer, 2013) According to Al-Muammar and khan 2015, the routine supplementation of Punica granatum may prevent or even correct obesity, diabetes and cardiovascular diseases.

1.2       JUSTIFICATION OF STUDY
Hypercholesterolemia is a problem faced by manysocieties since it constitutes one of the major risk factors for the development of cardiovascular diseases, such as atherosclerosis and its complications, acute infraction of themyocardium or hypertension (Robbins, 1991; Gerhardt and Gallo 1998; Gomeset al., 1998). In view of the adverse effects associated with hypercholesterolemia, the quest for natural products with lipid-lowering potential and with minimal or no side effect is needed.

1.3       AIM AND OBJECTIVES OF THE STUDY
The main aim of this research is to evaluate the effect of aqueous extract of Punica granatum seed on triton X-100 induced hypercholesterolemia in male albino rats.
In order to achieve the aim, the following specific objectives are followed.

• To estimate total phenol content in aqueous extract of Punicagranatum seed.
• To estimate invitro radical scavenging of power aqueous extract of Punicagranatum seed using 2, 2, diphenyl-1-picrylhydrazyl (DPPH) as substrate.
• To estimate inhibitory power of aqueous extract of Punicagranatum seed on lipase enzyme activity.
• To induce hypercholesterolemia in rats using Triton X-100.
• To study the effect of aqueous extract of Punica granatum seed on serum lipid profile of hypercholesterolemic rats.