THE SUPPRESSIVE ANTIMALARIAL EFFECT OF KHAYA GRADIFOLIA STEM-BACK IN MICE

THE SUPPRESSIVE ANTIMALARIAL EFFECT OF KHAYA GRADIFOLIA STEM-BACK IN MICE

CHAPTER ONE

INTRODUCTION

1.1       BACKGROUND OF THE STUDY

Antimalarial drug resistance is one of the greatest challenges of malaria therapy. Resistance accounts for recrudescence and severity of infections in some parts of the world (Peters, 1982). Many commonly used antimalarial drugs are chemically related such that development of resistance to one drug can result in resistance to others. For example, cross resistance between the 4-aminoquinolines, chloroquine and amodiaquine, has been reported (Bloland, 2001) as a result of ineffectiveness of commonly used antimalarial drugs, the use of alternative medicine either exclusively or along with conventional medicines has becomes common feature. This situation is prevalent in developing tropical countries where modern medicines are not affordable to a majority of the rural populations (Kremsner and Kritna, 2004).

Up to 80% of African population use traditional medicine especially plant remedies in the management of diseases including malaria (WHO, 2002). Often, antimalarial herbal therapies are used concurrently, prior or after the use of conventional antimalarial drugs in West Africa. Very few reports are available on the interaction of herbal anti-malarial products with synthetic drugs. One of such reports indicates that some local African populations use herbal products in combination with chloroquine for enhancement of activity (Rasoanaivo et al. 1998). Either of pharmacodynamic or pharmacokinetic interactions can result in synergism, additivity or antagonism. It is therefore most desirable to evaluate the interaction between common herbs used in the management of malaria and some of the conventional antimalarial drugs. More so, the use of combination of two or more drugs as a way of delaying or overcoming development of drug resistance is topical in malarial chemotherapy research (WHO, 2000). Combination of Artemisinin derivatives with other antimalarial drugs has become a standard practice in malaria chemotherapy.

Aqueous decoction of K. grandifoliola (Benin Mahogany or timber) is commonly used by traditional medical practitioners in West Africa in the management of malaria. This plant has been scientifically evaluated for its anti-malarial activity (Makinde et al 1989; Agbedahunsi et al, 1998), anti-inflammatory and toxic effects (Agbedahunsi et al, 2004), effects on red blood cells and bone mineral content in rats (Bumah et al, 2005a) and on some biochemical parameters in rats (Bumah et al, 2005b). A bicyclo (3, 3, 1) nonane derivative of phragmaline named grandifolioline, has been isolated from the anti-malarial fraction of this plant by Agbedahunsi et al. (1998). There is need to ascertain the suppressive antimalarial effect of KhayaGrandifolia Stem-Bark in mice.

1.2       STATEMENT OF THE PROBLEM

Malaria is a parasitic disease that affects more than 500 million people worldwide, killing between 60,000 (sixty thousand) and 2.7 million people annually, especially children and pregnant mothers (Percárioet al., 2012). It is caused by a single-celled parasite, Plasmodium. The parasite P. falciparum is usually transmitted to humans by a secondary vector, anopheles mosquitoes after a bite. Once in the body, Plasmodium has a complex life cycle and an inherent mechanism at evading the immune response. One of its key strategies is possession of high polymorphic natured proteins and the ability to undergo almost unlimited antigenetic variation by changing the antigens on the infected red blood cell surface. This inherent property results in significant challenges to vaccine design and rapid development of multi-drug resistant strains of Plasmodium. Drug resistant Plasmodium, particularly P. falciparum represents a major problem for both prophylaxis and clinical treatment of malaria infection (Phyo, 2012). There is a report of rapid spread of resistant malaria parasites to new areas and re-emergence of malaria in areas where the disease had been eradicated (McCollum, 2006). At present there are no drugs that can completely offer protection against malaria in all regions of the world.

Clinical resistance to the artemisinin and its combinations is currently being reported, suggesting that P. falciparum parasites have already developed the ability to grow in the presence of these antimalaria agents, leaving little or no alternative for malaria treatment. This strongly suggests the need for urgent and further research into new antimalarials (Noedl et al., 2008). Thus the need for this study to carry out a prophylactic antimalarial effect of ethanolic stem-bark extract of khaya grandifolia in mice.

1.3       AIM AND OBJECTIVES

The aim of this study is to ascertain the suppressive antimalarial effect of Khaya grandifolia stem-bark in mice.

1.4       SPECIFIC OBJECTIVES OF STUDY ARE

The specific objectives of this study are to:

1. To identify the antimalarial effect of Khaya grandifolia stem-bark in mice
2. To isolate active compounds from active fraction(s) of Khaya grandifolia
3. To determine the antimalarial effect of Khaya grandifolia in mice

1.5       SIGNIFICANCE OF STUDY

Malaria is a major health problem in Nigeria and Africa at large, it is widely diagnosed infectious disease in the country. It is the single most important cause of death especially among children under the age of 5 (23%); it is responsible for one out of ten deaths in pregnant women and causes the Federal Government of Nigeria over one billion Naira annually in treating malaria (Odugbemi, 2007). The disease is responsible for up to 60% of daily outpatient department (OPD) consultations in health facilities (FMOH, 2008). Chloroquine failure range of 50 – 95% has been reported for some parts of Nigeria (Faladeet al., 2005; FMOH, 2004). Report on the development of resistance to artemisinins and their associate drugs will cruelly limit the utility of ACT in future, leaving little or no alternative treatment or malaria. Consequently to develop alternative therapy, research on anti-malaria is urgently vital.

Lots of undocumented and unverified herbs are being used today as single and as poly-herbals in treatment of malaria fever. The diversity of chemical compounds found in these herbs could contribute greatly as an important source of molecular templates in the search for new and novel antimalarial drugs. Khayagrandifoliaroot bark, use in treatment of malaria fever was scientifically documented as a possibly safe, effective, affordable and active antimalarial agent. This study is therefore justifiable as it ascertain the suppressive antimalarial effect of Khaya Gradifolia stem-bark in mice.