Studies on anti-inflammatory act wity of extracts from seeds of picralima nitida

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1994-09-04
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Extracts from Picralima nitida (fam. Apocynaceae) were screened for anti- inflammatory activity. Administration of the aqueous ethanolic extract of P. nitida over the dose range 400 - 1600 mg kg-1 significantly, (p<0.05) suppressed the maximal oedema response (monitored as the percentage increase in paw thickness) attained during 6h of carrageenan-induced rat paw oedema (400 mg kg-1: 7.8%; 800 mg kg-1: 19.4%; 1600 mg kg-1: 37.8%). The total oedema response (monitored as the area under the time-course curve) was also significantly, (p<0.05) inhibited at the dose levels used by 17.3%, 28.2%, and 42.6% respectively. When administered at 800 and 1600 mg kg-1 prior to the induction of adjuvant-induced rat arthritis the crude extract P. nitida significantly, (p<0.05) inhibited the peak of the acute phase of the rat tibio-tarsal joint swelling by 5 1.0% and 17.3% respectively. The chronic phase of the joint swelling was inhibited by 24.1% and 68.4% respectively at the doses used. The total crude extract at 1600 mg kg-1 p.o. administered after the onset of the inflammatory responses reversed the course of both the carrageenan - and adjuvant-induced rat paw and joint swellings respectively. The total alkaloidal extract of P. nitida at 200, 400 and 800 mg kg-1 p.o., significantly inhibited the maximal carrageenan-induced rat paw oedema attained during 6h by 40.0%, 55.3% and 60.0% respectively. The doses caused significant, (p<0.05) inhibitions of the corresponding AUC’s by 49.3%, 61.4% and 68.3% respectively. The extract at 200 mg kg1 significantly, (p<0.05) suppressed both the acute and chronic phases of the adjuvant-induced rat tibio-tarsal joint swelling by 28.2% and 45.0% respectively and maintained the suppression of the adjuvant-induced swelling 10 days after drug withdrawal. The total alkaloidal extract, administered at 200 mg kg-1 p.o., after the induction of the inflammatory response reversed the course of the carrageenan-induced rat paw swelling. The compounds isolated from P nitida, akuammidine akuammicine and pseudo-akuammigine all significantly, (p<0.05) inhibited the maximal carrageenan-induced rat paw oedema by 23 9%, 29 0% and 34 4% respectively. The doses caused significant (p<0.05) inhibitions of the total carrageenan-induced rat paw oedema by 26.1%, 3 0.7% and 48.84% respectively. Akuamniine, administered at 100,200 and 400 mg kg1 significantly, (p<0.05) inhibited the maximal carrageenan-induced rat paw oedema by 25.59%, 32.3% and 45.54% respectively. The corresponding AUC’s were signiflcantly,(p<0.05) inhibited by 22.1%, 22.1% and 45.4% respectively. The most potent of the alkaloids tested on the carrageenan-induced rat paw oedema model, pseudo-akuammigine exerted a significant ,(p<0.05) analgesic activity which was 3.5 and 1.6 times less potent than morphine and indomethacin respectively on the mice tail withdrawal reflex model. It was significantly antagonised by naloxone implying an action mediated via narcotic receptors. The LD50 of Pseudo-akuammigine in male albino mice was 631.0 mg kg-1 per os. P. nitida seeds thus contain anti-inflammatory compounds, (namely akuammine, akuammidine, akuammicine and pseudo-akuammigine) which are potentially anti-arthritic. The most potent of the anti-inflammatory compounds (pseudo-akuammigine) also exerts significant analgesic actions.
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A thesis submitted In partial fulfilment of the requirements for the Master of Pharmacy Degree of the University of Science and Technology, Kumasi, Ghana, 1994
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