Chemotherapeutic Interactions of the Stem Bark of Khaya Grandifoliola (WELW) CDC (Meliaceae) Extract with Standard Antimalarial Drugs in Rodent Malarial Models

Ijarotimi, Oluwole Steve (2015-04-23)

Thesis

The study was aimed at investigating the interaction between K. grandifoliola stem bark extract and standard synthetic antimalarial drug (chloroquine and halofantrine) on blood schizontocidal activities. This was with a view to determine how the interaction between Khaya grandifoliola stem bark extract and standard synthetic antimalarial drugs (chloroquine and halofantrine) influences management of malaria. The K. grandifoliola stem bark, obtained from Igasi village in Akoko North West Local government Area of Ondo Stat, was chipped, dried at 60°C for 24 hours and powdered. A 600g of the powder was extracted with 50% ethanol using a Soxhlet extractor, the extract was concentrated to reduce the volume in vacuo and was finally lyophilized. Aqueous solution of the extract, chloroquine phosphate and halofantrine hydrochloride were prepared to give the following concentration dose ranges: K. grandifoliola, 50 - 400 mg/kg/day; Chloroquine 1.25 – 10 mg/kg/day and halofantrine, 6.25 - 50 mg/kg/day. Each of the doses of the plant extract and the standard drugs was daily orally administered separately or in combinations for four consecutive days to groups of mice infected with Plasmodium: yeoli nigeriense (n = 5) in an early malarial established malarial infection test models. The levels of parasite clearance due to the drugs were determined through preparation of the smear and viewed under the microscope using the x 100 objective lens. The results showed that K. grandifoliola stem bark extract gave 62 and 80% parasitic clearance at 200 and 400 mg/kg/day respectively. That was comparable to 78% for chloroquine at 10 mg/kg/day and 69% of halofantrine at 50 mg/kg/day. The parasite clearance due to combination of K. grandifoliola bark extract and halofantrine (100: 6.25 mg/kg/day) was significantly (p<0.05) higher (66%) than the parasite clearance due to separate administrations of K. grandifoliola bark extract (22%) and halofantrine (28%) at the tested doses. Also, the effects of combination of K. grandifoliola bark extract and chloroquine (100:2.5 mg/kg/day) gave parasite clearance of 55%. That was significantly (p<0.05) higher than 37% gave by chloroquine alone and 22% for K. grandifoliola bark extract alone at the tested doses. The study also showed that the parasite clearance in established infection for combination of K. grandifoliola bark extract and halofantrine (100:6.25 mg/kg) was significantly (p< 0.05) higher (70%) compared to 62% gave by the combination of K. grandifoliola bark extract and chloroquine (100:2.5 mg/kg). The mean survival period in established infection test was highest with the combination of K. grandifoliola bark extract and halofantrine (28 days), followed by halofantrine (25 days), chloroquine (18 days), K. grandifoliola bark extract and chloroquine (16 days) and K. grandifoliola bark extract (14 days). In conclusion, this study established that the parasite clearance and mean survival period of mice administered with combination of K. grandifoliola bark extract and standard drugs were significantly (p<0.05) higher than those gave by the extract, chloroquine and halofantrine alone. Therefore, K. grandifoliola bark extract and halofantrine combination was more active than the combination of extract and chloroquine.

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