IN VITRO ANTI LEISHMANIAL ACTIVITY OF SOME SELECTED MEDICINAL PLANTS IN GHANA

ABSTRACT
Leishmaniasis is a parasitic infection that affects mostly tropical and sub-tropical regions of the world and caused by diverse pathogens that belong to the genus Leishmania. The pentavalent antimonials developed in 1945 are still first line treatment drugs for both cutaneous and visceral leishmaniasis while amphotericin B is a second line treatment drug. These treatments come with toxic side effects even at effective doses and the lack of vaccine demand the urgent need for new anti leishmanial agents. This study aimed at investigating four plants used traditionally to treat parasitic infections. The collected plant parts were washed, dried, powdered and then extracted using ethanol. Different concentrations of the extracts ranging from 15.6 to 500 µg/mL in 0.1 % DMSO with M199 and a positive control of Amphotericin B were prepared in triplicates in 24-well plates that contained 117,000 parasites/well. The plates were incubated at 25 °C and promastigotes counted on 8, 12, 24 and 48 hours after incubation. Phytochemical screening on all crude extracts revealed the presence of steroids, triterpenoids, tannins, anthraquinons, saponins, alkaloids, flavonoids and glycosides. Of the four plants, Erythrophleum ivorense gave the best activity with an IC50 of 6.3 µg/mL after 72 hours. This was followed by C. oxycarpum, A. aubryanum and A. ahia respectively. Three compounds have been isolated from E. ivorense; erythroivorensin, eriodictyol and betulinic acid, with IC50s of 0.5, 61.8 and 247 µg/mL correspondingly on the promastigotes of L. donovani.


CHAPTER ONE
INTRODUCTION
Background
Leishmaniasis is an important parasitic disease that threatens the lives of millions of people worldwide and is caused by any of the numerous species of Leishmania (World Health Organization, 2013). The worldwide increase in the incidence of leishmaniasis has been mainly attributed to a surge in several risk factors that are clearly manmade (Desjeux, 2001). The disease presents in several forms depending on the type of species that is implicated and the immune response of the host (Herwaldt, 1999). In some forms, it is lethal, while in others, it has been described as a cruel mutilator leaving its victims scarred for life (Yanik, Gurel, Simsek, & Kati, 2004).

Anti-leishmanial vaccines are still being developed and as such the current control strategies for leishmaniasis rely on case management case such as detection and treatment, vector and reservoir control. Case management that includes early diagnosis and treatment is essential for both individual patients and for the community. There is reason to believe that the number of cases of leishmaniasis is on the rise (Desjeux, 1996) which could be due to artificial environmental changes which increase human exposure to the sand fly vector (Reithinger et al., 2007). Extracting timber, mining, building dams, widening areas under cultivation, new irrigation schemes, road construction, widespread migration from rural to urban areas and fast urbanization worldwide are among the main causes for an increased exposure to the sand fly (Reithinger et al., 2007).

Several treatments are available for the various groups of leishmaniasis. These drugs span from the ancient old antimonies to the most current miltefosin. Because most of the treatment drugs are old, their efficacy is limited presenting with several undesirable side effects (Chakravarty & Sundar, 2010; Diro et al., 2014; Lage, et al., 2013), making them far from satisfactory in their action even at the supposed effective doses. Drugs that are recommended for use in the treatment of cutaneous leishmaniasis and visceral leishmaniasis include the pentavalent antimonials which were first introduced nearly seven decades ago (Yardley & Croft, 2000). Over the past 20 years, alternative drugs or new formulations of other standard drugs have been presented and registered for use in some countries, whilst other drugs are on clinical trial for both forms of the disease (Yardley & Croft, 2000). However, serious side effects in the patients, prolonged treatment time, and increased parasite resistance have been draw backs over the years (Chakravarty & Sundar, 2010; Diro et al., 2014; Lage et al. 2013). Therefore, alternative drugs to the antimonials such as amphotericine B, pentamidine, paromomycin, and miltefosine have been recommended, but they also come with some problems and even therapeutic failure (Lage et al., 2013, Machado et al., 2012; Wiwanitkit, 2012).

The use of herbal medicine for the treatment of diseases and infections is as old as mankind (Surendra & Talele, 2011). The World Health Organization supports the use of traditional medicine provided they are proven to be efficacious and safe (Government of India, 2001). In the developing countries, vast numbers of people live in extreme poverty who suffer and die, for want of medicine among others, and lack alternative for primary health care (GOI, 2001). Therefore, the need to use medicinal plants as alternatives to orthodox medicines in the provision of primary health care cannot be over-looked. Herbal medicines now seem to be the remedy for both traditional and modern medicine (Zerehsaz et al., 1999). Additionally, herbal medicines have received much attention as sources of lead candidate compounds since they are considered as time tested and relatively safe for both human use and environmental friendliness (Fazly-Bazzaz, Khajehkaramadin, & Shokooheizadeh, 2005), including easily available and affordable. There is therefore, the need to look inwards to search for herbal medicinal plants with the aim of validating the ethno medicinal use and subsequently an isolation and characterization of compounds which will be added to the potential lists of drugs.

Modern synthetic drugs for leishmaniasis are simply not available or the few available ones are expensive while some come with adverse side effects. To obtain herbal medicine or an isolated active compound, different research strategies can be employed, among them are; the investigation of the traditional use, the chemical composition, the toxicity of the plants, or the combination of several criteria (Rates, 2001). For purification and isolation, the active extracts of the plant are sequentially fractionated, and each fraction and/or pure compound can be evaluated for biological activity and toxicity.

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Item Type: Ghanaian Project Material  |  Attribute: 134 pages  |  Chapters: 1-5
Format: MS Word  |  Price: GH110 ($20)  |  Delivery: Within 30Mins.
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