ANTI-PLASMODIAL ACTIVITY AND EFFECTS OF SCHWENKIA AMERICANA AND OLAX SUBSCORPIOIDEA EXTRACTS ON CYSTEINE PROTEASE FROM PLASMODIUM BERGHEI (NK 65) AND PLASMODIUM FALCIPARUM
ANTI-PLASMODIAL ACTIVITY AND EFFECTS OF SCHWENKIA AMERICANA AND OLAX SUBSCORPIOIDEA EXTRACTS ON CYSTEINE PROTEASE FROM PLASMODIUM BERGHEI (NK 65) AND PLASMODIUM FALCIPARUM
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Date
2018-11
Authors
BABA, Gabi
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Abstract
This study investigated the anti-plasmodial activity and inhibitory effect of extracts of Olax subscorpioidea, and Schwenkia americana on cysteine protease from P. falciparum and P. berghei(NK65). pLDH assay method was use in the antiplasmodial activity, while four-day suppressive activity method was used to evaluate the in-vivo anti-plasmodial activity against Plasmodium berghei (NK 65) strain. Isolation of the lead compounds, its characterization and structural identification by UPLC/LCMS, and NMR spectra analysis were accomplished, with data generatead via anti-plasmodial bio-assay guided fractionation. The variable from the schizont growth inhibition, IC50 and the enzyme inhibition profile were analysed statistically. The in-vitro antiplasmodial assay showed 82% of the screened, ethnobotanical identified plants extracts to be active against P. falciparum 3D7 strain with O. subscorpioidea and S. americana showing more promising activity with IC50 of 0.13 and 0.040 respectively. Such response lead to in-vivo study using murine strain which indicated parasite growth inhibition of P. beghei NK 65 in infected mice at dose ranges of 50 to 200mg/kg body weight. S. americana, O. subscorpioidea and S. seiberiana exhibited parasite suppression of 71.21±4.7 to 77.15±3.36, 72.52±7.57 and 77.42±10.84 and 32.22±12.69 33.74±15.65% respectively. Expressing all the extracts to be consider active at parasite suppressions ≥ 30%. Six active fractions of O. subscorpioidea against P. falciparum with IC50 range of 0.3 to 6.22μg/ml were identified, with GB003BC1.1 most active fraction with IC50 of 0.33μg/ml, which on further purification gave compounds identified to be Rel, 1β, 3α- dihydroxyl 7α, 9β dihydroxylcyclopentane (Octahydro-2-methyl-1H-indene-1, 3, 4, 6-tetraol) with IC50 1.65μg/mol and 1,2,3,4-tetrahydro-1-(1-hydroxybutan-2-yl)-4-methylnaphthalene-2,3-diol with IC50 1.79μg/ml both of which inhibits cysteine protease of P. berghei. Schwenkia americana however, gave seven fractions active against P. falciparum with 010EA2.3.1 fraction most active with IC50 1.75μg/ml, on further purification gave 010EA2.3.1G identified as compounds 2,5-dihydroxy-3-(2E,6E,10E) 3,7,11,15-tetramthylhexadeca-2,6,10,14-tetraenyl)cyclohexa-2,5-diene-1,4-dione, with IC50 2.92μg/ml which inhibits the cysteine protease of P. berghei and P. falciparum. The crude extracts effects were comparable to chloroquine with 84.52% inhibition. LD50 of the 3 plant extracts in rats and S. seiberiana and S. americana in mice were greater than 5000mg/kg body weight. While LD50 of O. Subscorpioidea in mice was 3800mg/kg body weight. Toxicity doses were 50 -100 times higher than active doses, the extracts can be used at lower doses within the shortest time of treatment with maximum benefits achieved and deleterious effect averted effectively.While identified compounds in the study are considered good candidates as potential anti-plasmodial agents with their activities concentration dependent, but reduces as purification progress.
Description
A PhD DISSERTATION SUBMITTED TO THE SCHOOL OF POSTGRADUATE STUDIES, AHMADU BELLO UNIVERSITY, ZARIA, NIGERIA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE AWARD OF THE DEGREE OF DOCTOR OF PHILOSOPHY IN BIOCHEMISTRY DEPARTMENT OF BIOCHEMISTRY, FACULTY OF LIFE SCIENCES AHMADU BELLO UNIVERSITY, ZARIA, NIGERIA
Keywords
ANTI-PLASMODIAL ACTIVITY,, EFFECTS,, SCHWENKIA AMERICANA,, OLAX SUBSCORPIOIDEA EXTRACTS,, CYSTEINE PROTEASE,, PLASMODIUM BERGHEI,, PLASMODIUM FALCIPARUM