Antiplasmodial compounds from Ghanaian medicinal plants
| dc.contributor.author | Komlaga, Gustav | |
| dc.date.accessioned | 2016-10-05T11:33:14Z | |
| dc.date.accessioned | 2023-04-20T21:39:25Z | |
| dc.date.available | 2016-10-05T11:33:14Z | |
| dc.date.available | 2023-04-20T21:39:25Z | |
| dc.date.issued | December 2015 | |
| dc.description | A thesis submitted in fulfillment of the requirements for the degree of Doctor of Philosophy (Pharmacognosy), The Department of Pharmacognosy, Faculty of Pharmacy and Pharmaceutical Sciences Kwame Nkrumah University of Science and Technology, | en_US |
| dc.description.abstract | Malaria is a major public health challenge in Ghana, and many indigenes employ medicinal plants, beside orthodox medicines, to treat the disease. An ethnobotanical survey was performed in the Bosomtwi and Sekyere East Districts of Ghana to identify plants used locally to manage malaria. This was done in comparison with the plant ingredients in marketed herbal antimalarial remedies in the Kumasi metropolis. The survey inventoried ninety-eight (98) plant species; twelve (12; 12.2%) reported for the first time globally, and twenty (20; 20.4%) others for the first time in Ghana for the treatment of malaria. Twenty-three (23) locally available finished, often multi/polyherbal antimalarial products examined contained aerial or underground parts of twenty-nine (29) of the plants cited in the survey as ingredients. Twenty-two (22) of these products were registered by the Ghana Food and Drugs Authority; four (4) were included in the Ghana Health Service recommended herbal medicine list for treating malaria in Ghana. The aqueous as well as serially extracted organic solvents (petroleum ether, ethyl acetate, and methanol) extracts of five plants parts, selected based on their importance in the traditional treatment of malaria and lack of the appropriate data in the literature, were studied against the chloroquine-sensitive 3D7 and chloroquine-resistant W2 P. falciparum parasite in vitro. The plant materials included the whole of Phyllanthus fraternus, leaves of Tectona grandis, Terminalia ivorensis and Bambusa vulgaris, and root of Senna siamea. All the aqueous extracts showed notable antiplasmodial activity (IC50 < 10 µg/mL), except that of S. siamea, against 3D7 P. falciparum. Only T. ivorensis and S. siamea extracts showed activity against W2 P. falciparum (IC50 < 50 µg/mL). The extracts demonstrated high selectivity index (SI) for 3D7 P. falciparum (SI > 3.5) but very low SI for W2 P. falciparum. Resistance index (RI) was largely under 20. The organic fractions were equally active (IC50 < 50 µg/mL; 3D7 P. falciparum). The methanol extracts of the two most potent plant materials, the whole of P. fraternus and leaf of B. vulgaris, were subjected to phytochemical study to isolate and elucidate the chemical constituents, which were then assayed for antiplasmodial activity. The phytochemical study of the v methanol extract of P. fraternus yielded six compounds; Pf 1 to Pf 6 identified as the lignan, phyllanthin, and five securinega alkaloids namely nirurine, ent-norsecurinine, allo-norsecurinine, bubbialine and epibubbialine. This is the first isolation of allo - norsecurinine from a natural source and bubbialine from the Phyllanthus genus. The compounds displayed significant antiplasmodial activity against both 3D7 and W2 P. falciparum (1.14 ± 0.32 µM ≤ IC50 ≤ 59.00 ± 5.43 µM); ent-norsecurinine being the most active (IC50=1.14± 0.32 µM) and against the W2 P. falciparum. Only Pf2 (nirurine) and Pf1 (phyllanthin) displayed cytotoxicity (CC50 < 100 μM; HUVECs). This is the first report of the antiplasmodial activity of these compounds. Similar study of the methanol extract of B. vulgaris yielded 6 compounds, Bv1 to Bv6, identified as p-coumaric acid [(E)-3-(4-hydroxyphenyl) acrylic acid], cinnamic acid, dehydrovomifoliol [(E)-4-hydroxy-3,5,5-trimethyl-4-(3-oxobut-1-en-1-yl)cyclohex- 2-en-1-one], 3-oxo-α-ionol [9-hydroxy megastigma-4, 7-dien-3-one], loliolide [6- hydroxy-4, 4, 7a-trimethyl-5, 6, 7, 7a-tetrahydrobenzofuran-2(4H)-one] and tricin [5,7,4’-trihydroxy-3’,5’-dimethoxyflavone]. The six compounds are the first everreported isolations from B. vulgaris. All the compounds from B. vulgaris displayed significant activity against 3D7 (IC50 < 5 μΜ and W2 strains of P. falciparum (IC50 < 7 μM). Bv1 (p-coumaric acid) was the most active against 3D7 P. falciparum (IC50: 0.84 ± 0.90 μM) and Bv2 (cinnamic acid) the most active against W2 P. falciparum (IC50: 1.41 ± 0.38 μM). The compounds displayed no cytotoxicity (CC50 > 100 μM; HUVECs). This is the first report of the antiplasmodial activity of the six compounds. These twelve (12) compounds with remarkable antiplasmodial activity add to the library of natural compounds with antiplasmodial activity. This study has illustrated the potentials of Ghanaian medicinal plants as source of natural antiplasmodial compounds, and has justified the use of the plants in traditional treatment of malaria. | en_US |
| dc.description.sponsorship | KNUST | en_US |
| dc.identifier.uri | https://ir.knust.edu.gh/handle/123456789/9091 | |
| dc.language.iso | en | en_US |
| dc.title | Antiplasmodial compounds from Ghanaian medicinal plants | en_US |
| dc.type | Thesis | en_US |
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