Antiplasmodial evaluation of extracts of selected Ghanaian medicinal plants and other bioactivities of isolates of polyalthia longifolia var. pendula (annonaceae)

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Date
2014
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Abstract
Malaria is one of the most important tropical infectious diseases. About half of the world’s population is at risk of developing malaria. It is a major public health challenge as well as a significant economic burden on many developing countries, especially in the African region. Most malaria patients are usually anaemic and also experience reduced or compromised immune systems which therefore predispose them to secondary bacterial and fungal infections. People living in extreme poverty are the most vulnerable to these infectious diseases simultaneously. This affects their ability to make a living and move out of poverty. Many of these people rely on herbs for treatment of the disease due to lack of access to efficacious antimalarial drugs against, especially the fast spreading multidrug-resistant Plasmodium falciparum. However, very few of these folklore herbs have been scientifically investigated and authenticated for used in the management of malaria and other infectious diseases. This study therefore sought to investigate and validate or otherwise the traditional uses of some Ghanaian plants for treating malaria. The ethanolic extracts of ten plant species which were selected based on their traditional medical application were screened against the multidrug resistant P. falciparum (K1 strain) by the parasite lactate dehydrogenase (pLDH) assay. Seven of the plant species (Adenia cissampeloides Planch. ex Hook. Anthocleista nobilis G. Don, Elaeis guineensis Jacq., Entandrophragma angolense (Welw.) CDC, Mallotus oppositifolius (Geisel.) Müll. Arg., Sarcocephalus latifolius (J.E.Sm) E. A Bruce and Polyalthia longifolia var. pendula) showed potent antiplasmodial activity with IC50 < 50 μg/ml. The extracts P. longifolia exhibited the most potent activity (IC50 < 23 μg/ml). Bioassay guided fractionation of P. longifolia extracts yielded four clerodane diterpenes [16- hydroxycleroda-3,13-dien-16,15-olide (1) and its acetylated derivative acetyl-16-oxycleroda- 3,13-dien-16,15-olide (1a), 16-oxocleroda-3,13E-dien-15-oic acid (2) and 3,16- dihydroxycleroda-4(18),13(14)Z-dien-15,16-olide (3)], a steroid [β-Stigmasterol (4)] and two vii alkaloids [Darienine (5) and L-Stepholidine (6)]. Even though the steroid and the alkaloids showed weak antiplasmodial activity (IC50: 22 -105 μg/ml), the clerodane diterpenes exhibited significantly (p < 0.005) potent blood schizonticidal activity (IC50: 3 - 6 μg/ml) against the multidrug resistant malaria parasite. Although the isolated clerodane diterpenes 1a, 2 and 3 are known compounds, this is the first report of their antiplasmodial activity especially against the multi-drug resistant Plasmodium falciparum. The clerodane diterpenes also displayed potent antibacterial and antifungal activities (MIC ranged between 3.13 and 50.00 μg/ml) against Staphylococcus aureus (ATCC 25923), Streptococcus pneumoniae (clinical isolate), Bacillus subtilis (NCTC 10073), Pseudomonas aeruginosa (ATCC 4853), Salmonella typhi (NCTC 8385), Escherichia coli (NCTC 25922) and Candida albicans (NCPF 3179). The study therefore appeared to lend support to the traditional uses of these plants as remedies for malaria in Ghana and formulations containing especially P. longifolia extracts will be highly beneficial in treating mixed infections associated with malaria.
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A thesis submitted to the Department of Pharmaceutics Faculty of Pharmacy and Pharmaceutical Sciences College of Health Sciences in fulfillment of the requirements for the degree of Doctor of Philosophy
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