ABSTRACT

Kaka bitters like other bitters is claimed to possess a number of folkloric therapeutic effects including lipid-lowering effects. However, there is no scientific data available as at the time of this study to evidence this claim. The Lipid-lowering effects of Kaka bitters were investigated by assessing it effects on the blood lipid parameters of wistar rats fed fat-enhanced diet. The was divided into three (3) groups: Group 1 rats was fed normal feed with distilled water; Group 2 was fed fat-enhanced diet with distilled water and Group 3 was fed fat-enhanced diet with Kaka bitters. The result obtained shows that blood TG levels decreased in group 3 rats compared with group 2, but the decrease is not statistically significant (p < 0.05). Also there was a statistically significant decrease in blood HDL levels and also statistically significant increase in total cholesterol and LDL levels of group 3 rats compared with group 2 (p < 0.05). The hyperlipidemic effect of Kaka bitters indicated by this result may be due to the alcoholic nature of Kaka bitters coupled with the antimicrobial effect of the bitters against the gut microbiota implicated in cholesterol metabolism and excretion. Kaka bitters is not a good therapy for treatment of dyslipidemia.

CHAPTER ONE

1.0    INTRODUCTION

Bitters as well as other medicinal plants have been the companions of man since time immemorial (Adaramoye, 2008). They occupy a central and integral place in modern herbal therapeutic medicine because of their efficacy and lesser toxicity compared synthetic drug. Many herbal remedies including bitters have been believed or known to be effective in management of dyslipidemia.

Dyslipidemia is a leading cause of coronary heart disease (CHD) and other related cardio- vascular disorders (CVDs). It is known that the occurrence of CHD is positively correlated with high total cholesterol and even more strongly with low density lipoprotein cholesterol. In contrast LDL Cholesterol, high level of HDL cholesterol has been associated with a decreased risk for heart disease (Clark et al, 2012). Efforts therefore have extensively been directed towards to reduce the risk of CVDs through the regulation of cholesterol (Adaramoye, 2008).

Kaka bitters like most other bitters is claimed to be an effective therapy for the management of abnormal blood lipid metabolism. However, there is a dearth of scientific data to support the folkloric use of this bitters in the treatment of abnormal lipid-related diseases (Adaramoye, 2008).

The present study therefore, was designed to provide scientific proof of the use of Kaka bitters in the management of dyslipidemia.

1.1     LITURATURE REVIEW

1.1.1 BITTERS – An Overview

1.1.1.1        HISTORY OF BITTERS

BIBLICAL VIEW       

Mentions of herbal bitters with therapeutic effects were made in the Christian Holy Bible bitters. The Psalmist, king David talked about the “herb for the service of man… which strengthened man’s heart” (Psalm 104: 14, 15 KJV). Apostle Paul mentioned “wine (liquor) for thy stomach’s sake (i.e. aperitif, digestif, carminative, etc.) and thine own infirmities (who knows, may be antimicrobial, anti-genotoxic, astringent, diuretic or laxative involving infirmities) 1 Timothy 5:23. The name “bitters” to mean these drinks was used in different bible passages including James 3:11.

CONTEMPORARY VIEW                                                                

It is in literature that the Angostura bitters was first compounded by a German physician, Dr. Johann Gottieb Benjamin Siegert in Venezuela in 1824 as a cure for sea sickness and had been discovered long before this. The bitter was reported to have effects of settling mild case of nausea, and also an apertif, digestive and carminative properties. The origin of herbal bitters has been tracked down to more than 5,000 years ago, possibly due to the opening of trade route with China (Oyewo et al, 2013b).

1.1.1.2        GENERAL MEDICINAL PROPERTIES OF BITTERS

Bitters generally are known to have

-          Anti-inflammatory and antiedemateous properties

-          Anti-HIV activity

-          Anti bacterial and antifungal activities

-          Anticancer and lymphocyte activation dual activities

-          Immuno-stimulant activity (Botanical, 2013)

-          Anti-oxidant activity

-          Hepato protective activity

-          Wound Heading activity

-          Spasmolytic and spasmogenic dual activities

-          Anti-viral activity (Sahu and pady, 2013)

-          Insecticidal activity

-          Heart inhibits

-          Genotoxic and anti genotoxic dual activities (Banaraso et al, 2009).

1.1.1.3 CHEMISTRY OF BITTERS

Bitters are many from different herbal extract, many of these plants are from the plant family, Asteraceae, which often sesquiterpene lactones. The primary active ingredients in most bitters include saponin, tannin, flavonoid, etc. That of blessed thistle is a bitter tasting sesquiterpene lactone called cnicin (Alam et al, 2011). The bitter principles in artichoke, burdock and milk thistle for instance are flavonolignans. Other glycosides such as those from bitter-fasting flavonoid glycosides such as those from bitter orange peel including neohesperidin and naringin (Kareem et al, 2009).

1.1.1.4   MECHANISM OF ACTION OF BITTERS

Bitter generally use bitter taste to elicit their effects. They act on the tongue receptor where their effects are carried to the various area of the brain  and further their signal they create are been interpreted and messages are appropriately sent out for their effect, for instance bitters elicit their effects as aperitifs by acting on the hypothalamus and increasing peristalsis.

There are fine distinct tastes that can be registered by the taste buds, viz: sally, sweet, bitter, sour, and umani or “savory”.

The bitter taste from bitters (a long sweet and umani taste) unlike salty and sweet bud taste which are sense by the taste bud through ion channels triggered by electronically charged particles, ions or certain food, are sensed by the taste bud through G-protein coupled receptors, a more sophisticated mechanism that is not well understand as that of ion channels. The compounds in bitters trigger certain molecules that close potassium ion channels, creating an action potential. Three cranial nerves are responsible for carrying the action potential initiated in taste buds to brain, where taste is ultimately registered. The facial nerve carries signals from the front two-thirds of the tongue and the vagus from the soft platelet and epiglottis.

1.1.2 BLOOD LIPIDS

1.1.2.1 INTRODUCTION

Plasma lipid consist of triacylglycerol (16%), phospholipids (30%), cholesterol (14%), and cholesteryl esters (36%) and much smaller fraction of unesterified long-chain fatty acid (4%) (Murray et al, 2003). This later fraction the free fatty acid is metabolically the most active in plasma lipid (Murray et al, 2003). Blood lipids such as triglycerides, phospholipids, and cholesterol possess oil nature and are not soluble (or sparing soluble) in blood. They are found noncovalently to protein to form lipoprotein (Voet and Voet, 2011). Lipoproteins are spherical macromolecular complexes of lipids (cholesterol and phospholipid especially) with specific proteins called apoproteins or apolipoprotein (Champe et al, 2008; Pellery and Goldan, 2011). Lipoprotein are globular micelle-like particles that consist of nonpolar core of triacylglycerol and cholesteryl esters surrounded by an amphiphilic coating of protein, phospholipid and cholesterol (Voet and Voet, 2011).  Macheboeut (1929) and Adair (1943) were the first people to work on lipoproteins. Plasma proteins are soluble in aqueous and weak salt solvents because of their protein components (Diribe et al, 1999).

1.1.2.2 GENERAL FUNCTIONS OF BLOOD LIPOPROTEINS

Blood lipoproteins have many functions including:

i.                    Function as transport vehicles for triacylglycerol and cholesterol to (and from) the body tissues (Voet and Voet, 2011; Champe et al, 2008).

ii.                  Function to keep their component lipid soluble in as the transport them in the blood (Champe et al, 2008).

iii.                Lipoproteins function to maintain structural integrity of cell surface and subcellular particles like mitochondria and microsomes (Deb, 2011).

iv.                 Lipoprotein changes in their plasma concentration in pathologies e.g. the β-lipoprotein increases in severe diabetes mellitus, atherosclerosis etc. Hence determination of the relative concentration of α- and β-lipoprotein and pre-β-lipoprotein are of diagnostic importance (Deb, 2011).

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