Analgesic and other pharmacological actions of extracts from the seeds of picralima nitida in rats

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The ethanolic (70 %) extract of Picralima nitida seeds were tested for anti- inflammatory and analgesic actions, using the carrageenan-induced rat paw oedema (Winter et al., 1962) and the rat tail withdrawal (Sewell and Spencer, 1976) respectively. The effect of diclofenac (6 mg/kg, p.o.) on the analgesic and anti- inflammatory actions of the extract (1.5 and 3.0 g/kg, p.o.) was investigated. The extract’s effects on activity of the isolated guinea pig ileurn and the rat cytochrome P450 protein content were investigated. The extract dose-dependently increased the mean pain threshold of rats to 65 ± 23.3 % and 118 ± 21.7% of the mean vehicle-treated control group. The extract (3.0 g/kg) also significantly (p <0.05) suppressed bradykinin-induced hyperalgesia in rats. The extract (1.5 and 3.0 g/kg, p.o.) dose-dependently suppressed the maximal carrageenan-induced rat paw oedema attained during 6 h by 28.8 ± 1.5 % and 55 ± 1.4 % respectively. Concurrent administration of the extract (1 .5 g/kg, p.o.) with diclofenac (6mg/kg, p.o.) produced significant (p<0.0l) analgesic activity but the combination effect was 1.9 times less potent than that of diclofenac alone and 1.3 times less potent than that of the extract alone. A higher dose of the extract (3.0 g/kg, p.o.) in combination with diclofenac (6 mg/kg, p.o.) did not offer any advantage over either drug administered alone at the same dose levels. The extract (50, 100 and 200 pg/ml) non-specifically inhibited the isolated guinea-pig ileurn contractions induced by nicotine, acetylcholine and histamine. Pre-treatment (3 days) of the rats with the extract (1 .5 and 3.0 g/kg, p.o.) dose-dependently decreased the pentobarbitone-induced sleeping time by 16.2 % and 64.8 % respectively. The effect was attributed to an inductive effect on hepatic cytochrome P450 system enzymes. Hepatic microsomal cytochrome P450 content in rats previously treated with extract (3.0 g/kg) was increased by 71 %. Thus, Picralima nitida seed extract contain compounds that are potentially anti- inflammatory and analgesic. The extract in addition to its known opioid analgesic actions also has antagonistic actions on bradykinin-induced hyperalgesia. The extract also induces rat cytochrome P450 enzymes. It is suggested that this action be further investigated since it has important clinical significance for patients who may take picralima extracts concurrently with other medications. The extract should also be further investigated to isolate the possible bradykinin antagonists and determine if they are selective on any bradykinin receptor subtype.
A Thesis submitted to the Department of Pharmacology, Kwame Nkrumah University of Science and Technology, In partial fulfillment of the requirements for the degree of Master of Pharmacy, 2004