ABSTRACT
Malaria is one of the most debilitating tropical parasitic diseases and the greatest cause of hospitalization and death. Recurring problems of drug resistance are reinforcing the need for finding new antimalarial drugs. In this respect, natural plant products are the main sources of biologically active compounds and have potential for the development of novel antimalarial drugs. The present study was designed to elucidate bioactive metabolite and in vivo antimalaria efficacy of crude and solvent fractions of Polyalthia longifolia against Plasmodium berghei in mice. The crude methanol extract of the plant was analysed for the presence of bioactive metabolites following standard procedure. A rodent malaria parasite, Plasmodium berghei, was used to inoculate healthy male Swiss Albino mice of age 6-8 weeks and weight 28- 35 g. Crude methanol extract and the solvent fractions were administered at different doses 150, 300 and 600 mg/kg. Parasitaemia, survival time, body weight, and packed cell volume were determined using standard tests. The results indicated the presence of phytochemicals including flavonoids, phenols, tanins, and alkaloids. Saponin content (500.76±2.37 mg/100 g) was significantly higher than other phytochemicals detected. Acute oral toxicity bioassay reveals an LDso extrapolated to be above 1600 mg/kg body weight. The crude extract at doses 600 mg/kg b.wt showed appreciable antiplasmodial potency than the fraction. The crude extract prevented loss of weight and slightly affected packed cell volume. The solvent fraction also prevented loss in packed cell volume. All doses of crude extracts and fractions of P. longifolia leaf prolong the survival time of infected mice in a dose dependent pattern. The results collectively indicate that the plant has a promising antiplasmodial activity against Plasmodium berghei, which upholds the earlier in vitro findings as well as its folkloric use.
CHAPTER ONE
1.0 INTRODUCTION
1.1 Background to the Study
Malaria, a parasitic infection caused by a protozoan of the genus Plasmodium,
contributes substantially to the poor health situation in Africa. About 90 % of the world’s
216 million cases and 65 5 000 annual deaths of malaria occur in the sub-Saharan African region (World Health Organization, (WHO), 2012). In Nigeria, more than 3 million cases are reported annually. A significant proportion (900,000) of such cases occurs in children under the age of five (WHO, 2014). Malaria has an immense effect on people of all ages but children under five years, pregnant women and immigrants from non-endemic regions are the most vulnerable because of their low immunity (Neelavathi et al., 2013). It is a major cause of absenteeism from school in endemic countries and frequent episodes of severe malaria in young children may negatively impact on their learning abilities and educational attainment. According to WHO/UNICEF (2013), about 2 % of children who recover from cerebral malaria suffer brain damage including epilepsy. In pregnant women, malaria can cause anaemia, miscarriages, stillbirths, underweight babies and maternal deaths. Malaria is therefore, a threat to human capital accumulation, which constitutes a key factor in economic development (Asante and Asenso-Okyere, 2003). The devastating impacts of malaria on adult victims are also very much disturbing. It causes considerable pain and weakness in the victims which translate into reduced working abilities. A single bout of the disease in a young adult costs an equivalent of working days. It has also put an unbearable strain on household resources as malaria care can cost up to 34 % of a poor household’s income (Asante and Asenso-Okyere, 2003; Fana et al., 2015). This adversely and substantially impact on gross domestic product. In
endemic countries, malaria causes a negative effect on growth of tourism, investments and trade and loss of productivity on the major sectors of their economies (Perkins and Austin, 2011 ). In Africa, the low productivity and high mortality resulting from malaria has been estimated to cost US$ 12 billion in lost Gross Domestic Product (GDP) and has also slowed economic growth by 1.3 % every year. Malaria control in the sub-region is key to achieving five of the eight millennium development goals (i.e. Eradicating extreme poverty and hunger, achieving universal primary education, reducing child mortality rates, improving maternal health, combating HIV/AIDS, malaria, and other diseases). Control
measures of the disease include prevention of infection, treatment of infected people and control of the mosquito vector. Great efforts have been made to eradicate malaria all over the world. The WHO in 1955 launched the Global Malaria Eradication Program which aggressively employed effective treatment of the infection (with chloroquine) and control of the mosquito vectors (with DDT insecticide) (Kantele & Jokiranta, 2011). Even though this program helped to eradicate the disease in nations with temperate climates and seasonal malaria transmission, many other nations such as Indonesia, Haiti, Afghanistan and Nicaragua, recorded negligible achievements. The hyper endemic countries in the sub-Saharan Africa region were however completely excluded from this eradication campaign (WHO, 2008).
In Nigeria, malaria control has been high on the public health agenda as far back as pre• independence with preventive interventions including indoor residual and aerial spraying with insecticides and the addition of Pyrimethamine to table salt (Wellems, 2002; Adams et al., 2004). However, the widespread mosquito resistance to insecticides, inaccessibility of health services in the rural areas, proliferation of fake and substandard antimalarial drugs in the sub-region and the emergence of multidrug-resistant malaria parasites, has hampered the goal of these control measures. Treatment of malaria with potent, effective, available and affordable drugs nevertheless, remain crucial to the control and the eventual eradication of the disease in Nigeria and the sub-region as a whole. Many antimalarial chemotherapeutic agents have been used to treat the infection but most of these agents are now not effective due to the widespread of multidrug-resistant malaria parasites (Asante and Asenso-Okyere, 2003).
1.2 Statement of the Research Problem
Despite more than a century of efforts to control or eradicate malaria, the disease remains a major growing threat to public health and economic development of countries in the tropical and sub-tropical world. This has been largely attributed to P. falciparum resistance to most antimalarial drugs (Achan, et al., 2011).
In Nigeria, malaria transmission occurs throughout the year round, and the country accounts for a quarter of all malaria cases in the World Health Organization (WHO), African region (WHO, 2008). Most malaria cases are caused by P. falciparum, although they remain unconfirmed.
Malaria endemic regions of the world are faced with an unprecedented situation in which affordable treatment options are rapidly losing therapeutic efficacy because of some degree of resistance (Batista, et al., 2009). As a consequence of drug resistance, drugs like quinine, chloroquine, primaquine and mefloquine are ineffective in treating malaria in many endemic regions of the world (CDC, 2012). Another problem relating to drug resistance in P. falciparum is the occurrence of cross-resistance among drugs belonging to the same chemical family (WHO, 2001). Even though no clinically relevant artemisinin resistance has been reported yet, it is likely to occur since artemisinin resistance has been obtained in laboratory animals (Bayor, 2007). Plasmodium falciparum is reported to have reduced in vivo susceptibility to artesunate in Western Cambodia, historically part of a site of emerging antimalarial-drug resistance (Bhatta, et al., 2011 ).
1.3 Justification for the Study
Some of the reasons for increase in mortality due to malaria include; P. falciparum resistance to most anti-malarial drugs, Anopheles mosquito’s resistance to insecticides, environmental changes, war and civil disturbances, travels and cross border movements. The main reason, however, is parasite resistance to antimalarials which complicates the problem of treatment. In the absence of a functional, safe, inexpensive and widely available malaria vaccine, the effort to develop new antimalarial drugs from local plants traditionally reputed to cure malaria becomes profoundly important.
One of the strategies in the search for new anti-malarial compounds is the study of active constituents (metabolites) of medicinal plants. Generally, scientific information about antimalarial activity of plants traditionally acclaimed to cure malaria is very limited or does not exist in some cases. Phytochemical screenings of medicinal plants are not only used to search for bioactive agents but also help to reveal the presence of agents in plants which serve as starting products for the partial synthesis of some useful drugs. It is therefore important to screen medicinal plants for antimalarial activity in order to ascertain their potentials as sources of new anti-malarial compounds. The reputed efficacies of Polyalthia longifolia have been documented. However, lack of scientific proof claimed by traditional healers in Nigeria necessitates a scientific study on this plant. It is in light of this, that Polyalthia longifolia have been screened for antimalarial activities.
1.4 The Aim of the Study
The aim of this study is to evaluate bioactive metabolite and in vivo antimalaria efficacy of crude and solvent fraction of Polyalthia longifolia in Plasmodium berghei.
1.5 Objectives
The objectives of the study are to determine:
1. phytochemical constituent of the crude extract of Polyalthia longifolia.
11. median lethal dose (LDso) of the extract (crude) of Polyalthia longifolia.
111 . the antiplasmodial activities of the crude and fraction of P. longifolia 1v. the effect of the crude and fractionated extract on body weight, packed cell volume, and haematological parameters of P. berghei-infected mice
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ANTI-PLASMODIAL EFFECTS OF POLYALTHIA LONG/FOL/A (VAR.) LEAF EXTRACTS AGAINST PLASMODIUM BERGHEIN MICE
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