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ANTI-PLASMODIAL EFFECTS OF POLYALTHIA LONG/FOL/A (VAR.) LEAF EXTRACTS AGAINST PLASMODIUM BERGHEIN MICE

Amount: ₦15,000.00 |

Format: Ms Word |

1-5 chapters |



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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