Thesis Abstract

Abstract
Hyperlipidemia is a major risk factor for cardiovascular diseases, and the search for effective therapeutic agents to manage lipid disorders is ongoing. This study aimed to investigate the anti-hyperlipidemic potential of Vitex doniana ethanolic extracts in both poloxamer 407-induced hyperlipidemic and normal rats. Male wistar rats were divided into six groups normal control, hyperlipidemic control, hyperlipidemic rats treated with atorvastatin (standard drug), and hyperlipidemic rats treated with three different doses of Vitex doniana ethanolic extracts (100 mg/kg, 200 mg/kg, and 400 mg/kg). The treatment was administered orally for 14 days. The results showed that poloxamer 407-induced hyperlipidemia significantly increased serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and very low-density lipoprotein cholesterol (VLDL-C) levels while decreasing high-density lipoprotein cholesterol (HDL-C) levels when compared to the normal control group. Treatment with Vitex doniana ethanolic extracts reversed these changes in a dose-dependent manner. The highest dose of 400 mg/kg exhibited the most significant reduction in TC, TG, LDL-C, and VLDL-C levels, along with a substantial increase in HDL-C levels. Furthermore, the histopathological examination of the liver tissues indicated that poloxamer 407-induced hyperlipidemia caused hepatic steatosis, which was attenuated by treatment with Vitex doniana ethanolic extracts. The extracts showed hepatoprotective effects by reducing lipid accumulation and preserving the normal architecture of the liver tissue. In conclusion, the findings of this study suggest that Vitex doniana ethanolic extracts possess anti-hyperlipidemic properties in both hyperlipidemic and normal rats. The extracts effectively regulated lipid profile parameters and exhibited hepatoprotective effects against poloxamer 407-induced hepatic steatosis. Further studies are warranted to elucidate the underlying mechanisms of action and to determine the potential of Vitex doniana as a natural alternative for managing hyperlipidemia and associated complications.

Thesis Overview

Anti-hyperlipidemic potential of extracts (aqueous, 70% methanol, 70% ethanol and 70%, acetone) of Vitexdoniana leaves, stem bark and root bark on poloxamer 407 induced hyperlipidemic and normal rats was investigated. Phytochemical screening of the extracts revealed the presence of flavonoids, saponins, cardiac glycosides, alkaloids and tannins in the leaves, stem bark and root bark. The average total polyphenol contents of the leaves ethanol (36.11±3.13mg/g gallic acid) and methanol (35.75±1.72mg/g gallic acid) extracts were significantly (p<0.05) higher when compared with that of acetone and aqueous extracts. The IC50of the leaves ethanol extract (0.227mg/ml) was lowerthan that ofstem bark ethanol extract (0.236mg/ml) and root ethanol extract (0.561mg/ml). Screening the extracts for the most potent anti-hyperlipidemicactivityreveals that ethanolic extracts of root bark and leaveshas the highest percentage reduction of total cholesterol (51.98%) and triacylglycerol (50.75%) respectively. The most abundant phytochemical in the most potent extract is flavonoid (4.605±0.077%) in the leaves and the least is tanins (0.035±0.008%) in the root bark extract. The LD50 of both leaves and stem bark was greater than 5000mg/kg body weight and that of root bark was 948.68 mg/kg body weight. Hyperlipidemic control rats significantly (p<0.05) increased total Cholesterol (TC), Triacylglycerol (TAG), Low density lipoprotein (LDL-c) andsignificantly (p<0.05) decreased High density lipoprotein (HDL-c) compared to other groups.Atherogenic risk factor of all induced treated rats shows a significant (p<0.05) lower levels of LDL-c/HDL-c, Log (TAG/HDL-c) and significant (p<0.05) higher level of HDL-c /TC ratio. There was no significant (p>0.05) change between normal control rats and normal treated rats in lipid profile parameters and atherogenic indices. The level of liver marker enzymes (ALT, ALP, AST) and liver function parameter (TB, IB) were significantly (p<0.05)higher, and lower (TB, DB) in hyperlipidemic control groups compared to all other groups. The invivo antioxidant activity shows a significantly (p<0.05) higher level of TBARS and a significant (p<0.05) lower level of SOD and CAT in hyperlipidemic groups when compared to all treated groups. In both liver and kidney, the leaves and stem bark extract significantly (p<0.05) lowers levels of TBARS of normal control rats compared to normal treated and all induced treated groups. All the extracts activity in the liver and leaves extract in the kidney of normal rats show a significant higher level of CAT compared with other treated groups. The study shows that vitexdoniana possesses anti-hyperlipidemic potential.

INTRODUCTION

Polyphenols arenaturalorganic chemicals characterized by the presence of large number of phenol structural units (Quideauet al., 2011). The most research-informed and chemistry-aware definition of polyphenol is termed the White–Bate-Smith–Swain–Haslam (WBSSH) definition (Haslam and Cai, 1994) which describes the polyphenol as moderately water-soluble compounds, with molecular weight of 500–4000 Dalton,having more than 12 phenolic hydroxyl groups and with 5–7 aromatic rings per 1000 Da.The number and characteristics of the phenol structures underlie the unique physical, chemical, and biological properties of a particular member of the polyphenol class(Quideau et al., 2011).

Over the past 10 years, researchers and food manufacturers have become increasingly interested in polyphenols. The main reason for this interest is the recognition of the antioxidant properties of polyphenols, their great abundance in our diet, and their probable role in the prevention of various diseases associated with oxidative stress, such as cardiovascular, cancer and neurodegenerative diseases. As the major active substance found in many medicinal plants, itmodulates the activity of a wide range of enzymes and cell receptors.Polyphenols as antioxidants, helps in addressing and reversing the problems caused by oxidative stress to the walls of arteries, create a heart-healthy environment by curbing the oxidation of low density lipoprotein cholesterol which stops the potential for atherosclerosis, and they help relieve chronic pain, as seen in conditions like rheumatoid arthritis, due to their anti-inflammatory properties. In addition to having antioxidant properties, polyphenols have several other specific biological actions that are yet to be understood(Quideau et al., 2011). Plants has been a source of medicinal agents for thousands of years, and an impressive number of modern drugs have been isolated from natural sources, many based on their use in traditional medicine (Hostettmann et al., 2000). These plants continue to play an essential role in health care, with about 90% of the world‟s inhabitants depending mainly on traditional medicines for their primary health care (Hostettmann et al., 2000). Recently, there has been an upsurge of interest in the therapeutic potentials of medicinal plants antioxidants reducing free radical related diseases. It has been mentioned that the antioxidant activity of plants might be due to their phenolic compounds (Cook and Samman, 1996).