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CHAPTER ONE
1.0 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
20
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).
Vitex doniana is a deciduous tree, usually 4-8m high, with a dense rounded crown. Its
bark is light grey with numerous vertical fissures. The leaves are long stalked with 5-7
leaflets. The leaflets are usually widest towards the tip, more or less hairless. The fruits
are ellipsoid to oblong, green turning black on ripening. It is a savanna species in wooded
grassland and can also be found along forest edges. It is extremely widespread in tropical
Africa. It is commonly known as Black Plum or African olive (Glew et al., 1997), Dinya
(Hausa),Galbihi (Fulani),Oori-nla (Yoruba), Ucha coro (Igbo), and is wide spread in the
southwestern Nigeria as a perennial tree. Earlier reports have shown that aqueous root
bark extract of the plant can be used for the treatment of anaemia (Abdulrahman et al.,
2010), methanolic stem bark extract can be used for the treatment of gastroenteritis,
diarrhoea, dysentery (Kilani, 2006) and aqueous leaves and stem bark extracts for the
treatment of liver disorder (James et al., 2010). The ability of an aqueous extract of Vitex
21
doniana stem bark to protect the liver of albino rats from carbon tetrachloride-induced
liver damage was reported by Ladeji and Okoye (1996).
Hyperlipidemia is an elevation of one or more of the plasma lipids, including cholesterol,
cholesterol esters, triglycerides and phospholipids (Raasch, 1988). It is the most common
form of dyslipidemia. It is well established that elevated blood lipid levels
(hyperlipidemia)constitute the primary risk factor for atherosclerosis (Saunders, 2007).
There is now overwhelming evidence that, dietary factors, nutritional habits and genetic
origin influence the risk of coronary artery diseases (Van Horn, 1997). Increased levels of
high-density lipoprotein cholesterol (HDL-c) are associated with a decreased
cardiovascular risk (Wanner and Quaschning 2001; Kourounakisetal., 2002,).
Predominant cardiovascular diseases associated with hyperlipidemia arehypertension,
ischemic heart diseases, stroke, coronary heart diseases and atherosclerosis.They account
for at least 80% of the burden of cardiovascular disease in both developing and developed
countries, which shares many of the same common risk factors (Balakumar et al., 2007).
Hyperlipidemia is divided into primary and secondary subtypes. Primary hyperlipidemia
is usually due to genetic causes such as a mutation in a receptor protein, while secondary
hyperlipidemia arises due to other underlying causes such as diabetes. (Chait and
Brunzell, 1990). Traditionally, factors such as hypercholesterolemia, cigarette smoking,
diabetes mellitus and sedentary life style have been implicated in the development of
hyperlipidemia and atherosclerotic cardiovascular disease (Frohlich and Lear, 2002).
22
1.1 Statement of Research Problem
Hyperlipidemia is one of the greatest risk factors contributing to the prevalence and
severity of cardiovascular disease (Grundy, 1986). It accounts for about 56% of stroke,
18% of ischemic heart disease and more than 4 million deaths per year globally (WHO
2002).In Nigeria, it accounts for about (45–73) % death per year (Ebesunum et. al.,
2008). Cardiovascular diseases are one of the major causes of death worldwide (Murray
and Lopez, 1996).Although several factors, such as diet high in saturated fats and
cholesterol, age, family history, hypertension and life style play a significant role in
causing heart failure.High levels of cholesterol particularly total cholesterol, triglycerides
and low density lipoprotein cholesterol is mainly responsible for the onset of CHDs
(Choudhary et al., 2005). About 20% reduction of blood cholesterol level can decrease
about 31% of CHD incidence and 33% of its mortality rate (Marzyieh et al., 2007).
Cardiovascular disease covers a wide array of disorders, including disease of the cardiac
muscle and of the vascular system supplying the heart, brain, and other vital organs
(Bently et al., 2002). Predominant cardiovascular diseases associated with hyperlipidemia
are hypertension, ischemic heart disease, stroke, coronary heart disease and
atherosclerosis (Balakumar et al., 2007). Hyperlipidemia is asymptomatic, characterized
by elevated serum total cholesterol, low density lipoprotein, very low density lipoprotein
and decreased high density lipoprotein levels.Hyperlipidemia associated with lipid
disorders are considered to cause atherosclerotic cardiovascular diseases (Saravanan et.
al., 2003). Among these are hypercholesterolemia, hypertriglyceridemia and ischemic
heart disease (Kaesancini and Krauss, 1994).
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1.2 Justification
Polyphenols are natural products found in fruits and vegetables, as well as in beverages
such as tea and red wine. Recent datasuggests that diet rich in these compounds is
associated with a decreased risk of cardiovascular diseases such as atherosclerosis,
ischemic heart disease, stroke, coronary heart disease and hypertension. Their effects are
also believed to underlie part of the improved cardiovascular health ascribed to the
„French paradox‟. Polyphenols are hypothesized to provide cardio-protective effects
through their ability to scavenge free radicals and inhibit lipid peroxidation. As
antioxidants, they help 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 LDL cholesterol, and they help relieve chronic pain, as seen in conditions
like rheumatoid arthritis , due to their anti-inflammatory properties.
Recent works are available on the scavenging potential of the aqueous extract of Vitex
doniana in the treatment of carbon tetrachloride induced liver damage, but there is no
documentated work on the effect of itsethanol extractson hyperlipidemic rats.Hence there
is a need to investigate the effect of these extracts on hyperlipidemic rats.
1.3 Aim and Objectives
The general aim of this study is to investigate theantihyperlipidemic effect of ethanol
extracts from different parts (leaves, stem and root bark) ofVitex doniana in therats, with
a view of providing a pharmacological justification and for the use of the plant in the
management, control and/or treatment of hyperlipidemic relateddiseases.
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1.3.1 Specific objectives
1. To carry out the plant phytochemicalscreening, extracts total polyphenol and in vitro
antioxidant activity.
2.To carry out in vivoantihyperlipidemic activity of the extractsand quantitative
phytochemical of most potent extract.
3. To determine the effect of the extract onlipid profile andsomebiochemicalparameters
of the hyperlipidemic and normal rats.
4.To determine the effect of the extract on lipid peroxidationand endogenous antioxidant
enzymesin hyperlipidemic and normal rats.
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