ANTIPLASMODIAL ACTIVITY OF COMBINED METHANOLIC LEAVES EXTRACT AND BARK EXTRACTS OF Anogeisus leiocarpus AND Terminalia avicennioides AND ITS EFFECT ON THE KIDNEY IN MICE INFECTED WITH Plasmodium ber
CHAPTER ONE
1.0 INTRODUCTION
Malaria is a mosquito-borne infectious disease of humans and other animals caused by parasitic protozoans belonging to the genus Plasmodium, (WHO 2014). Malaria causes symptoms that typically include fever, fatigue, vomiting, and headaches. In severe cases it can cause yellow skin, seizures, coma or death, (Caraballo 2014). The disease is transmitted by the biting of mosquitos, and the symptoms usually begin ten to fifteen days after being bitten. If not properly treated, people may have recurrences of the disease months later (WHO 2014). In those who have recently survived an infection, reinfection usually causes milder symptoms. This partial resistance disappears over months to years if the person has no continuing exposure to malaria (Caraballo 2014).
The disease is widespread in the tropical and subtropical regions that exist in a broad band around the equator, (Caraballo 2014). This includes much of Sub-Saharan Africa, Asia, and Latin America. Malaria is commonly associated with poverty and has a major negative effect on economic development(Gollin et al., 2007; Worrall et al., 2005). In Africa, it is estimated to result in losses of US$12 billion a year due to increased healthcare costs, lost ability to work, and negative effects on tourism (Greenwood et al., 2005). The World Health Organization reports there were 198 million cases of malaria worldwide in 2013 (WHO 2014;GBD 2013). This resulted in an estimated 584,000 to 855,000 deaths, the majority (90%) of which occurred in Africa(WHO 2014,(WHO 2015).
The disease is most commonly transmitted by an infected female Anopheles mosquito. The mosquito bite introduces the parasites from the mosquito's saliva into a person's blood (WHO 2014). The parasites travel to the liver where they mature and reproduce. Five species of Plasmodium can infect and be spread, (Caraballo 2014). Most deaths are caused by P. falciparum because P. vivax, P. ovale, and P. malariae generally cause a milder form of malaria (WHO 2014; Caraballo 2014). The species P. knowlesi rarely causes disease in humans (WHO 2014).
The risk of the disease can be reduced by preventing mosquito bites by the use ofmosquito nets and insect repellents, or with mosquitocontrol measures such as spraying insecticides and draining standing water (Caraballo 2014). Several medications are available to prevent malaria in travellers to areas where the disease is common. Occasional doses of the medication sulfadoxine/pyrimethamine are recommended in infants and after the first trimester of pregnancy in areas with high rates of malaria. Despite a need, no effective vaccine exists, although efforts to develop one are ongoing, (WHO 2014).
The recommended treatment for malaria is a combination of antimalarial medications that includes an artemisinin, (WHO 2014; Caraballo 2014). The second medication may be either mefloquine, lumefantrine, or sulfadoxine/pyrimethamine, (WHO 2010).Quinine along with doxycycline may be used if an artemisinin is not available, (WHO 2010). It is recommended that in the tropics, malaria infection should be confirmed if possible before treatment is started due to concerns of increasing drug resistance. Resistance among the parasites has developed to several antimalarial medications; for example, chloroquine-resistant P. falciparum has spread to most malarial areas, and resistance to artemisinin has become a problem in some parts of Southeast Asia (WHO 2014).With the present episode of development of drug resistant malaria parasite to the artemisinin which was believed to be the hope of effective treatment of malaria infection, there is a need for the development of new drugs and therefore UNESCO had encouraged all localities to look inwardly for the effective the treatment of malaria locally (UNESCO 1998; Atawodi et al., 2011).
The use of medicinal herbs has been a common method of treating malaria among the people living in malaria endemic areas (Ahmad 2014;Shuaibu et al., 2008). This practice has also been part of Nigeria culture especially in the rural areas where they do not have access to the good hospitals and most people living in these areas are peasant farmers who cannot afford to buy antimalarial drugs which are highly potent (Akanbi et al., 2012; Idowu et al., 2010). At present, most people who live in urban areas in Nigeria sometimes prefer to use the medicinal plants for the treatment of malaria as a result of emergency of the resistance of malaria parasites to anti-malarial drugs. Some of the medicinal plants used for treatment of malaria in Nigeria include, Terminalia avicennioides, Anogeissus leiocarpus, Morinda lucida, Citrus medica, Azadirachta indica(Akanbi et al., 2012).
The signs and symptoms of malaria typically begin 8–25 days following infection (Fairhurs et al., 2010).However, symptoms may occur later in those who have taken antimalarial medications as prevention (Nadjm et al., 2012). Initial manifestations of the diseasecommon to all malaria speciesare similar to flu-like symptoms, (Bartoloni et al., 2012)and can resemble other conditions such as sepsis, gastroenteritis, and viral diseases, (Nadjm et al., 2012). The presentation may include headache, fever, shivering, joint pain, vomiting, hemolytic anemia, jaundice, hemoglobin in the urine, retinal damage, and convulsions (Beare et al., 2006). The classic symptom of malaria is paroxysma cyclical occurrence of sudden coldness followed by shivering and then fever and sweating, occurring every two days (tertian fever) in P. vivax and P. ovale infections, and every three days (quartan fever) for P. malariae. P. falciparum infection can cause recurrent fever every 36–48 hours, or a less pronounced and almost continuous fever (Ferri2009).
Severe malaria is usually caused by P. falciparum (often referred to as falciparum malaria). Symptoms of falciparum malaria arise 9–30 days after infection (Bartoloni et al., 2012). Individuals with cerebral malaria frequently exhibit neurological symptoms, including abnormal posturing, nystagmus, conjugate gaze palsy (failure of the eyes to turn together in the same direction), opisthotonus, seizures, or coma (Bartoloni et al., 2012). Several scientific investigations of medicinal plants have been initiated in many communities and countries of Africa because of their contributions to healthcare, (Willcox and Bodeker, 2005). An impressive number of modern drugs have been isolated from plant origin in the traditional medicine, (Newman and Cragg, 2007). There are two well-known antimalarials of plant origin, quinine and artemisinin, both of which are prescribed to malaria patients globally. Nigerian traditional healers have long history of usage of plants to prevent or cure infections including malaria fever (Gbadamosi et al., 2010; Idowu et al., 2010; Odugbemi et al., 2007). Several extracts from medicinal plants used traditionally to treat malaria were reported for their antiplasmodial activities, (Adebayo and Krettli, 2011; Adumanya et al., 2012; Jigamet al., 2010). Some of the medicinal plants used for the treatment of malaria in Nigeria include: Terminalia avicennioides, Anogeisus leiocarpus, Morinda lucida, Citrus medica, Azadirachta indica, Momordica balsamina, Combretum paniculatum and Trema guineensis. All these plants have been reported to contain alkaloids, tannins, flavonoids and anthraquinones, but in variable degrees (Akinyemi et al., 2005).
1.1 AIM AND OBJECTIVE
1.1.1 General objective
This work assessed the efficacy of the methanolic leaf and bark extract of Anogeisus leiocarpus and Terminalia avicennioidescombination therapy against malaria parasite and its effect on the kidney of mice infected with Plasmodium berghei.
1.1.2 Specific objective
To test for the significance difference in Plasmodium berghei parasite elimination efficacy between combined methanolic leaves extract and bark extracts of Anogeissus leipcarpus and Terminalia avicennioides.
To determine the efficacy of combined methanolic leaves extract and bark extracts of Anogeissus leiocarpus and Terminalia avicennioides at different dosage.
To assess the effect of methanolic leaves extract and bark extracts of Anogeissus leiocarpus and Terminalia avicennioides on; Potassium (K+), Creatinine (Cr), Serum Glumatic Oxaloacetic Transmutase (SGOT), Serum Glutamic Pyruvic Transmutase, (SGPT).
1.0 INTRODUCTION
Malaria is a mosquito-borne infectious disease of humans and other animals caused by parasitic protozoans belonging to the genus Plasmodium, (WHO 2014). Malaria causes symptoms that typically include fever, fatigue, vomiting, and headaches. In severe cases it can cause yellow skin, seizures, coma or death, (Caraballo 2014). The disease is transmitted by the biting of mosquitos, and the symptoms usually begin ten to fifteen days after being bitten. If not properly treated, people may have recurrences of the disease months later (WHO 2014). In those who have recently survived an infection, reinfection usually causes milder symptoms. This partial resistance disappears over months to years if the person has no continuing exposure to malaria (Caraballo 2014).
The disease is widespread in the tropical and subtropical regions that exist in a broad band around the equator, (Caraballo 2014). This includes much of Sub-Saharan Africa, Asia, and Latin America. Malaria is commonly associated with poverty and has a major negative effect on economic development(Gollin et al., 2007; Worrall et al., 2005). In Africa, it is estimated to result in losses of US$12 billion a year due to increased healthcare costs, lost ability to work, and negative effects on tourism (Greenwood et al., 2005). The World Health Organization reports there were 198 million cases of malaria worldwide in 2013 (WHO 2014;GBD 2013). This resulted in an estimated 584,000 to 855,000 deaths, the majority (90%) of which occurred in Africa(WHO 2014,(WHO 2015).
The disease is most commonly transmitted by an infected female Anopheles mosquito. The mosquito bite introduces the parasites from the mosquito's saliva into a person's blood (WHO 2014). The parasites travel to the liver where they mature and reproduce. Five species of Plasmodium can infect and be spread, (Caraballo 2014). Most deaths are caused by P. falciparum because P. vivax, P. ovale, and P. malariae generally cause a milder form of malaria (WHO 2014; Caraballo 2014). The species P. knowlesi rarely causes disease in humans (WHO 2014).
The risk of the disease can be reduced by preventing mosquito bites by the use ofmosquito nets and insect repellents, or with mosquitocontrol measures such as spraying insecticides and draining standing water (Caraballo 2014). Several medications are available to prevent malaria in travellers to areas where the disease is common. Occasional doses of the medication sulfadoxine/pyrimethamine are recommended in infants and after the first trimester of pregnancy in areas with high rates of malaria. Despite a need, no effective vaccine exists, although efforts to develop one are ongoing, (WHO 2014).
The recommended treatment for malaria is a combination of antimalarial medications that includes an artemisinin, (WHO 2014; Caraballo 2014). The second medication may be either mefloquine, lumefantrine, or sulfadoxine/pyrimethamine, (WHO 2010).Quinine along with doxycycline may be used if an artemisinin is not available, (WHO 2010). It is recommended that in the tropics, malaria infection should be confirmed if possible before treatment is started due to concerns of increasing drug resistance. Resistance among the parasites has developed to several antimalarial medications; for example, chloroquine-resistant P. falciparum has spread to most malarial areas, and resistance to artemisinin has become a problem in some parts of Southeast Asia (WHO 2014).With the present episode of development of drug resistant malaria parasite to the artemisinin which was believed to be the hope of effective treatment of malaria infection, there is a need for the development of new drugs and therefore UNESCO had encouraged all localities to look inwardly for the effective the treatment of malaria locally (UNESCO 1998; Atawodi et al., 2011).
The use of medicinal herbs has been a common method of treating malaria among the people living in malaria endemic areas (Ahmad 2014;Shuaibu et al., 2008). This practice has also been part of Nigeria culture especially in the rural areas where they do not have access to the good hospitals and most people living in these areas are peasant farmers who cannot afford to buy antimalarial drugs which are highly potent (Akanbi et al., 2012; Idowu et al., 2010). At present, most people who live in urban areas in Nigeria sometimes prefer to use the medicinal plants for the treatment of malaria as a result of emergency of the resistance of malaria parasites to anti-malarial drugs. Some of the medicinal plants used for treatment of malaria in Nigeria include, Terminalia avicennioides, Anogeissus leiocarpus, Morinda lucida, Citrus medica, Azadirachta indica(Akanbi et al., 2012).
The signs and symptoms of malaria typically begin 8–25 days following infection (Fairhurs et al., 2010).However, symptoms may occur later in those who have taken antimalarial medications as prevention (Nadjm et al., 2012). Initial manifestations of the diseasecommon to all malaria speciesare similar to flu-like symptoms, (Bartoloni et al., 2012)and can resemble other conditions such as sepsis, gastroenteritis, and viral diseases, (Nadjm et al., 2012). The presentation may include headache, fever, shivering, joint pain, vomiting, hemolytic anemia, jaundice, hemoglobin in the urine, retinal damage, and convulsions (Beare et al., 2006). The classic symptom of malaria is paroxysma cyclical occurrence of sudden coldness followed by shivering and then fever and sweating, occurring every two days (tertian fever) in P. vivax and P. ovale infections, and every three days (quartan fever) for P. malariae. P. falciparum infection can cause recurrent fever every 36–48 hours, or a less pronounced and almost continuous fever (Ferri2009).
Severe malaria is usually caused by P. falciparum (often referred to as falciparum malaria). Symptoms of falciparum malaria arise 9–30 days after infection (Bartoloni et al., 2012). Individuals with cerebral malaria frequently exhibit neurological symptoms, including abnormal posturing, nystagmus, conjugate gaze palsy (failure of the eyes to turn together in the same direction), opisthotonus, seizures, or coma (Bartoloni et al., 2012). Several scientific investigations of medicinal plants have been initiated in many communities and countries of Africa because of their contributions to healthcare, (Willcox and Bodeker, 2005). An impressive number of modern drugs have been isolated from plant origin in the traditional medicine, (Newman and Cragg, 2007). There are two well-known antimalarials of plant origin, quinine and artemisinin, both of which are prescribed to malaria patients globally. Nigerian traditional healers have long history of usage of plants to prevent or cure infections including malaria fever (Gbadamosi et al., 2010; Idowu et al., 2010; Odugbemi et al., 2007). Several extracts from medicinal plants used traditionally to treat malaria were reported for their antiplasmodial activities, (Adebayo and Krettli, 2011; Adumanya et al., 2012; Jigamet al., 2010). Some of the medicinal plants used for the treatment of malaria in Nigeria include: Terminalia avicennioides, Anogeisus leiocarpus, Morinda lucida, Citrus medica, Azadirachta indica, Momordica balsamina, Combretum paniculatum and Trema guineensis. All these plants have been reported to contain alkaloids, tannins, flavonoids and anthraquinones, but in variable degrees (Akinyemi et al., 2005).
1.1 AIM AND OBJECTIVE
1.1.1 General objective
This work assessed the efficacy of the methanolic leaf and bark extract of Anogeisus leiocarpus and Terminalia avicennioidescombination therapy against malaria parasite and its effect on the kidney of mice infected with Plasmodium berghei.
1.1.2 Specific objective
To test for the significance difference in Plasmodium berghei parasite elimination efficacy between combined methanolic leaves extract and bark extracts of Anogeissus leipcarpus and Terminalia avicennioides.
To determine the efficacy of combined methanolic leaves extract and bark extracts of Anogeissus leiocarpus and Terminalia avicennioides at different dosage.
To assess the effect of methanolic leaves extract and bark extracts of Anogeissus leiocarpus and Terminalia avicennioides on; Potassium (K+), Creatinine (Cr), Serum Glumatic Oxaloacetic Transmutase (SGOT), Serum Glutamic Pyruvic Transmutase, (SGPT).
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