ABSTRACT

 Kola bark extract have been widely used in tradition medicine for thousand of year, it improves liver functions and provides protection against high fat fed metabolic rats. Present investigations were carried out on the hepatoprotective role of Kola bark extract meal treatment to high fat fed wistar rat. Healthy adult male wistar rats were divided into four groups Group I: rats were fed a standard Laboratory diet (groups match) (20g/rat/day), Group II: rats were fed a high-fat diet alone (3.6g/rat/day), Group III: rats were fed with combined mixture of 70% of high-fat diet with 30% Kola bark meal (9.8g/rat /day), Group/ V: rats were fed with high fat diet and was administered with Lipitor (Atovastatin) (10mg/rat/day) . The rats were sacrificed at the end of the experiment (two weeks) period. The high fat fed rat substantially elevated its serum and liver tissue AST, ALT, ALP, bilirubin with decreased in total protein levels. Where as the levels of all parameters significantly restored towards normalization by the kola bark husk meal treatment. The results obtained suggest that the Kola bark meal have potent hepatoprotective action on high fat fed rats. A companion of the performance in both Kola bark meal and Lipitor treatment on high fat fed rat in respect of hepatoprotective role is clearly indicator that the Kola bark meal treatment was more and related to the result of Lipitor as well as to the normal level.

 List of tables

Table 1: Test for Cholesterol (TC)

 Table 2: Test for Triglyceride (TG)

 Table 3: Qualitative Analysis: Phytochemical Composition of samples

 Table 4: Qualitative Analysis: Quantitative Phytochemistry

 Table 5: Liver Function Test of rats fed with various samples

 2.0  Literature review

2.1       Origin of kola 

2.1.2 Strategies for enhancing investment opportunities in kola production-

2.2 Lipid metabolism

 2.2.1 Lipid and lipoproteins –definition and classification

 2.2.2. Plasma lipoproteins

 2.3.4 Cholesterol metabolism

2.3.0 Liver x receptor

2.3.1 Liver x receptor as cholesterol sensors

2.3.2 Liver x receptor and bile acid synthesis, metabolism and excretion

2.3.3 LXR and cholesterol Biosynthesis

2.3.4 LXR and cholesterol uptake -

2.3.5 LXR and intestinal cholesterol absorption

2.3.6        LXR as therapeutic targets  

CHAPTER THREE

 3.0  Materials and methods

3.1  Identification of plant material

3.2  Phytochemical analyses

3.3  Experimental animal models

3.4  Collection of blood sample

3.5  Lipid profile analysis

CHAPTER FOUR

 4.0   Results

4.1  Discussions

CHAPTER FIVE

CHAPTER ONE

1.0 INTRODUCTION BACKGROUND OF THE STUDY

Liver is the largest and most complex internal organ in the body. It plays an important role in the maintenance of internal environment through its multiple and diverse functions. Liver is involved in several vital functions such as metabolism, secretion and storage. Hepatitis or inflammatory disorder involves inflammation and damage to the hepatocytes. Hepatitis is one of the most prevalent diseases in the world. Every year 18,000 people had been reported to die due to liver cirrhosis caused by viral hepatitis [L] Ectopic fat storage occurs in obesity particularly in the liver leading to a condition termed nonalcoholic fatty liver disease [NAFLD] characterized by varying degree of liver injury that progresses from steatosis to tratohepatitis, fibrosis and necrosis Due to its prominent association with IR (insulin resistance). Obesity, NAFLD is regarded as the hepatic manifestation of metabolite [3] syndrome. Liver has great capacity to detoxicate toxic substances.

Kola pod is the traditional health food around the world. Kola pod Husk meal is the residue after grinding the pod of kola and filtration, and it is an excellent source in slightly high in fiber (16.74%), low in crude protein (9.98%), moderate NFE (42.391) and metabolizable energy 2497 kcal/kg, and ash content is relatively high. (13.26%). when companied with the values reported by (Oluokun, 1999) ;(Hamzat and Babatunde, 2001). These differences might be due to varietals differenced and shelf life of the test ingredient before analysis. However, the crude protein content fairly put kola pod husk meal (KPHM) with feed ingredients like Sorghum while the fibre content put it in same proximate com being one of the important pods for medical treatment in the world. The kola pod husk provides some essential materials for doth drying. The pod bark, when mixed with some ingredients is used in traditional medicine to reduce Labour pains. The bark is used in treating swellings and fresh wounds. The roots provide excellent chewing sticks for cleaning the teeth and the wood is used in local carvings coachwork and boatbuilding. Lipid refers to the different kind of fats present in the bodies of human plasma include triglyceride (TG), phospholipids (PL), cholesterol esters (CE), and free cholesterol (FC) and non-esterified fatty acid (NEFA. Each lipid plays a different role in our bodies yet all of them except free cholesterol (FC) contain esters of long chain fatty acid in their structures. Lipids are insoluble in plasma due to their non- polar structures thus; they need some carriers that are soluble in polar and non- polar environment. Lipids are packaged and carried in the form of lipoprotein, which is a molecule that contains both protein (i.e. apolipoprotein) and lipids.

Statins (lipitor) are group of drugs approved for their Cholesterol reduction properties and are commonly used to treat atherosclerosis and coronary artery disease. These drugs inhibit 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-COA) reductase. The rate limiting enzyme in cholesterol biosynthesis; which converts HMG.CoA to mevalonate. Apart from cholesterol, mevalonate is also the substrate for the synthesis of nonsteroid, isoprenoids such as coenzyme Q. Depletion of these isoprenoids results in the so called plelotropic effects of statins which are independent of cholesterol.

Lowering effect.These plelotropic effects of anti-inflammatory, anti-apoptotic and ant-proliferative effect. In addition, data from experimental and observational studies indicated that statins have neuroprotective effects and be a treatment option for neurodegenerative diseases of the central nervous system and the ocular structures particularly the retina (schemer, 2007). Statins (Atorvastatin) is widely used in the treatment of hepatic diseases. They have been widely used in chinning proactive as cholesterol lowering agents to reduce mobility and mortality from coronary artery diseases. It also has an effect in inflammatory diseases such as rheumatoid arthritis, and multiple sclerosis.

However, limited studies are available on the effect of kola pod husk meal treatment on hepatoprotective effect in high fat diet fed animal in this regard, the present study was aimed to investigate the effect of kola pod meal on high-fat fed rats related to different hepatoprotective effect by comparing Lipitor Treatment.

CHAPTER TWO

LITERATURE REVIEW

 2.1  Origin of kola

The gems Kola of the family sterculiaceae (Russel, 1955), is indigenous to tropical Africa and has its centre of greatest diversity in west Africa in the forest areas of west Africa, kola is perhaps second only to palm oil in importance in the list of indigenous cash crops. About 40 kola species have been described in West Africa. However, in Nigeria, the kola species of real importance are kola acuminate and kola nitida

(Quarcoo,1973;(Daramola,1978) Kola acuminate and Kola nitida are important economic crops in the forest areas of west and central Africa, carribean islands, mauritivs, Sri Lanka and Malaysia (Eijnatten,1969);( Oladokun, 1985). The cultivation of cola nitida in Nigeria began sometime in the 19^th century. The nitida―goro)wasobservednut‖tobe (kolagrowing abundantly in the otta bush in 1854 while its cultivation was noted in Egba Division in 1902 and in Labochi and envious in 1901. From Agege, kola nitida cultivation presumably spread to the forest areas following first the course of the railway line into Abeokuta, Ibadan and Offa replacing the local kola acuminata and penetrating later along streams and river banks into the Guinea savannah and at present, south and Eastern state (Eijnatte, 1969).

Kola nuts have for hundreds of years served as an important article of internal trade in Nigeria and other parts of Africa (Nzekwu, 1961). It has been an item of trade in West Africa and in the Trans-saharan trade routes for many countries (Egbe and Sobamiwa, 1989).

Kola nut is used as a masticatory stimulant by Africans and has numerous uses in social, religious, ritual and ceremonial functions by the natives in the forest region of Africa it is used during ceremonies related to marriage, child naming, installation of chiefs, funeral and sacrifices made to the various gods of Africa Mythology (Nzekwu, 1967) ;( Daramola, 1978) ;(Opeke, 1992). There is also increasing demand for its usage in pharmaceuticals industries and for production of soft drinks, wines, and candles (Beattie, 1970); Ogutuga, 1975). Its uses have inevitably created a high demand in excess of its production (Oladokun, 1985).

Kola nut has been used as abuse for a now brand of chocolate and wine (Kola chocolate and kola wine) which were developed by CRIN researchers (famuyima, 1987). Eka, (1971), has also reported the possible use of pulverized kola nuts for the preparation of non-alcoholic beverages.

Kola pod husk has also been utilized for the production of liquid soap. The most recent and remarkable advancement is kola by-product utilization is the use of kola pod husk in the replacement of up to 60% of the maize used in

pottery feed formulations (yahayaet al, 2001); (Hamzat, 2001);( Hamzat and Babatunde, 2001) ;( Hamzat and longe, 2002) ;( Hamzatet al; 2000) ;( Olubamimaet al, 2002). Other uses of kola according to Nzekwu (1961) are as follows: - (1) It provides some essential materials for doth dying. (2) The pod bark, when mixed with some ingredients is used in traditional medicine to induce labour pains. (3) The bark is used in treating swellings and fresh wounds. Research on the improvement of productivity of kola is carried out at the cocoa research institute of Nigeria (CRIN) with the mandate in Nigeria for research into production and extension aspects of cocoa, kola, coffee, cashew and tea.

2.1  Strategies for enhancing investment opportunities in kola production.

1.      The first step is to improve the quality and quantity of kola nut production in the country. This can be achieved by two approaches.

2.      Rehabilitation of kola orchards: a more efficient utilization of land can be achieved by the cutting down of unproductive trees and replacing them with proven materials.