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Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/9076

Title: Bioactive anti-leishmanial agents: prospects of the Ghanaian biodiversity
Authors: Ackah Armah, Francis
Issue Date: 5-Oct-2016
Abstract: Leishmaniasis, one of the neglected tropical diseases, is currently a significant health problem in North Africa with a rising concern in West Africa because of co-infection with the Human Immunodeficiency Virus (HIV). The aim of this research is to evaluate the anti-leishmanial, anti-inflammatory and antioxidant activities of methanol extracts of four (4) indigenous plants namely root bark of Erythrophleum ivorense and the stem barks of Coelocaryon oxycarpum, Omphalocarpum ahia and Anthostema aubryanum and determine the chemical constituents which confer on the species their purported activities in folklore medicine. These plants are traditionally used in Ghana to treat parasitic infections as well as pain and inflammation. In vitro anti-leishmanial potential of the selected plants was evaluated using direct counting assay of promastigotes of Leishmania donovani. Amphotericin B was used as positive control. Anti-inflammatory activity of the extracts and compounds were evaluated using the chick carrageenan model with diclofenac and dexamethasone as standards. The antioxidant potential of the extracts and compounds were also evaluated using the DPPH scavenging assay. E. ivorense showed the highest anti-leishmanial activity (IC50 = 14.10 μg/mL), followed by A. aubryanum (IC50 = 23.90 μg/mL), C. oxycarpum (IC50 = 31.31 μg/mL) and O. ahia (IC50 = 124.04 μg/mL) respectively. E. ivorense thus showed considerable activity compared to amphotericin B (IC50 = 2.4 μg/mL). Fractionation of E. ivorense afforded a moderately active ethyl acetate fraction and a significantly methanol fraction active (IC50 = 2.97 μg/mL). E. ivorense also showing the highest anti-inflammatory (ED50 = 16.91 mg/kg body weight) and antioxidant (IC50 = 1.11 μg/mL) activities, followed by C. oxycarpum, O. ahia and A. aubryanum respectively. Investigation of the pet-ether, ethyl acetate and methanol fractions of E. ivorense revealed the ethyl acetate fraction to be the most active. Further fractionation of the ethyl acetate fraction led to an isolation of the novel cassane diterpene erythroivorensin as well as the flavanone eriodictyol and the triterpene betulinic acid. The rank order of leishmanicidal potency of the compounds was erythroivorensin (IC50 = 29.10 μg/mL) > eriodictyol (IC50 = 103.80 μg/mL) > betulinic acid (IC50 = 1000 μg/mL). These compcounds may be working synergistically to produce the observed anti-leishmanial activity of the ethyl acetate fraction. The anti-inflammatory activity of betulinic acid (ED50 = 4.367±1.333 mg/kg body weight), the most active anti-inflammatory compound, was comparable to that of diclofenac (ED50= 3.74±0.333 mg/kg body weight). This was followed by erythroivorensin (ED50 = 18.66±0.667 mg/kg body weight) and eriodictyol (ED50 = 56.25±0.133 mg/kg body weight). With respect to the antioxidant activity of the compounds, eriodictyol was the most active (IC50 = 21.06 μg/mL), followed by betulinic acid (IC50= 33.07 μg/mL) and erythroivorensin (IC50 = 35.78 μg/mL) respectively. The present studies have shown that extracts of E. ivorense have considerable anti-leishmanial activity and could be used for the treatment of leishmaniasis after the establishment of its toxicity profile. The novel compound erythroivorensin possesses anti-leishmanial effects and has considerable anti-inflammatory properties. To the best of my knowledge, eriodictyol and betulinic acid are isolated for the first time in Erythrophleum ivorense.
Description: A thesis submitted in fulfilment of the requirements for the degree Of Doctor Of Philosophy In the Department of Pharmacognosy Faculty of Pharmacy and Pharmaceutical Sciences College of Health Sciences Kwame Nkrumah University of Science and Technology By Francis Ackah Armah May, 2016
URI: http://hdl.handle.net/123456789/9076
Appears in Collections:College of Health Sciences

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