EVALUATION OF ANTIMALARIAL POTENTIAL OF CYSTEINE PROTEASE INHIBITORS FROM CALOTROPIS PROCERA LINN AND MORINGA OLEIFERA LAM ON PLASMODIUM BERGHEI INFECTED MICE

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dc.contributor.authorABDULKADIR, ABDULLAHI
dc.date.accessioned2018-09-07T08:41:01Z
dc.date.available2018-09-07T08:41:01Z
dc.date.issued2017-10
dc.descriptionA DISSERTATION SUBMITTED TO THE POSTGRADUATE SCHOOL, AHMADU BELLO UNIVERSITY, ZARIA, NIGERIA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE AWARD OF THE DEGREE OF THE DOCTOR OF PHILOSOPHY IN BIOCHEMISTRY DEPARTMENT OF BIOCHEMISTRY FACULTY OF LIFE SCIENCES AHMADU BELLO UNIVERSITY, ZARIA, NIGERIAen_US
dc.description.abstractCysteine protease of Plasmodium parasite plays a major role in the survival of the organism inside its host. Various extraction media were used to evaluate different parts of Calotropis procera and Moringa oleifera for Cysteine Protease inhibitor (CPI) activity. The latex of C.procera and M.oleifera seeds extracts with higher CPI activity were concentrated by cold acetone precipitation, further subjected to purification using ammonium sulphate fractionation and Phenyl sepharose column and characterized. Subchronic toxicity of the extracts was evaluated in mice after intraperitoneally (ip) administering different doses for 21 days. A 4-day suppressive antimalarial test was carried out using Plasmodium berghei NK65-infected mice, to which the extracts were administered at different doses intraperitoneally. The partially purified CPIs from C.procera and M.oleifera, exhibited inhibitory activities of 31.47 units/mg proteins and 11.23 units/mg protein respectively. The partially purified inhibitors have optimum temperature at 600C and 500C for C.procera and M.oleifera respectively. The pH optimal for C.procera and M.oleifera are 6.0 and 7.0 respectively. The partially purified inhibitors from both plants were stable at temperatures below 600C for 6 hours and were active at wide range of pH values from 2 to 12. Chemical modification of the some key amino acids present in the binding site of CPI, revealed the presence Cysteine and Histidine for C.procera latex and Lysine for M.oleifera seeds.The kinetic analysis revealed a mixed type of inhibition for both inhibitors against Plasmodium berghei cysteine protease enzyme. The fifty percent inhibitory concentration (IC50) values of 23.10±1.2 μg/ml and 17.2±0.3 μg/ml with inhibitor binding constant (Ki) values of 8.0μg/ml and 20.0μg/ml for both inhibitors suggested high affinity between inhibitors and enzymes. Serum biochemical parameters evaluated which included Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatinine for subchronic toxicity were not significantly (P<0.05) altered at all doses of the extract used. There was significantly (P<0.05) elevated serum glucose at 30 and 50mg/kg BW/day for crude CPI extract of C.procera latex. A significantly (P<0.05) reduced Triacylglycerol level was observed at all doses of crude CPIs extract from M.oleifera seeds treated group compared to the control group. However, the partially purified CPI extract of C.procera latex reduced parasitaemia by 77% at a dose of 50 mg/kg. BW, while partially purified CPI extract of M.oleifera seeds reduced parasitaemia by 57% at a dose of 70 mg/kg BW on day 8-posttreatment.The crude and purified CPIs extract from both plants improved the survival of animals compared to control group. The disease-induced decreases in packed cell volume (PCV) were ameliorated by treatment with CPIs extract. It can be concluded from the results obtained in this study that partially purified CPI from the plants extracts at the dose and route used could be possible antidote against malaria.en_US
dc.identifier.urihttp://hdl.handle.net/123456789/10291
dc.language.isoenen_US
dc.subjectEVALUATION,en_US
dc.subjectANTIMALARIAL POTENTIAL,en_US
dc.subjectCYSTEINE PROTEASE INHIBITORS,en_US
dc.subjectCALOTROPIS PROCERA LINN,en_US
dc.subjectMORINGA OLEIFERA LAM,en_US
dc.subjectPLASMODIUM BERGHEI INFECTED MICEen_US
dc.titleEVALUATION OF ANTIMALARIAL POTENTIAL OF CYSTEINE PROTEASE INHIBITORS FROM CALOTROPIS PROCERA LINN AND MORINGA OLEIFERA LAM ON PLASMODIUM BERGHEI INFECTED MICEen_US
dc.typeThesisen_US
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