Anti-nociceptive and central nervous system effects of the stem bark extracts of Trichilia Monadelpha (Thonn.) JJ De Wilde (Meliaceae)

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Trichilia monadelpha (Thonn.) JJ de Wilde (fam. Meliaceae) is used in Ghanaian and other African traditional medicine for the treatment of various painful and inflammatory conditions. This study therefore examined the anti-nociceptive and central effects of the petroleum ether, ethyl acetate and hydroalcoholic extracts of the stem bark of Trichilia monadelpha in various animal models. Preliminary phytochemical screening of the extracts revealed the presence of alkaloids, flavonoids, glycosides, saponins, sterols, tannins and triterpenes in the hydroalcoholic extract. The ethyl acetate extract showed the presence of alkaloids, glycosides, tannins and triterpenes whiles petroleum ether extract showed the presence of alkaloids, sterols and triterpenes. All three extracts (10-100mg kg-1, p.o.), together with morphine and diclofenac (positive controls) showed significant dose-dependent anti-nociceptive activity in the chemical (acetic acid abdominal writhing and formalin tests), thermal (hot plate test) and inflammatory (carrageenan-induced mechanical hyperalgesia test) pain models in rodents. The anti-nociceptive effect of the systemic administration of hydroalcoholic extract was partly or wholly reversed by atropine (a non-selective muscarinic cholinergic receptor antagonist), naloxone (a non-selective opioid receptor antagonist), theophylline (a non-selective adenosine receptor antagonist) and glibenclamide (an ATP-sensitive K+ channel inhibitor). The anti-nociceptive effects of the systemic administration of ethyl acetate extract and petroleum ether extract were partly or wholly reversed by atropine. Yohimbine, a selective α2-adrenoceptor antagonist however did not alter the anti-nociception produced by all three extracts. These results indicate that all three extracts produce dose-related anti-nociception in various animal models of chemical, thermal and inflammatory pain through mechanisms that involve an interaction with muscarinic cholinergic, adenosinergic, opioidergic pathways and ATP-sensitive K+ channels. The petroleum ether extract however was the most potent. The central effects of the extracts were evaluated in various behavioural models-elevated plus-maze and the light-dark box tests. All three extracts (10-100 mg kg-1, p.o.) displayed possible central nervous system depressant activity (sedation) by decreasing the time spent by mice in the light compartment and the number of transitions in the light-dark box test. There was a decreased in open arm entries and risk assessment behaviours such as unprotected forms of stretch attend postures and head dips in the elevated plus-maze test. All three extracts (10-100 mg kg-1, p.o.) did not modify the motor performance effects in the rotarod test but conversely decreased motor coordination in the beam traversal test, which is a more sensitive test able to identify motor deficits in mice. This effect in motor impairment may be ascribed to the reported central nervous system depressant (sedative effects) of the plant as having sedative effects in the hypno-sedative pentobarbitone sleeping time test. In summary, the study has shown that the petroleum ether, ethyl acetate and ethanolic extracts of Trichilia monadelpha stem bark have anti-nociceptive activity with some sedative effects.
A Thesis submitted to the School of Graduate Studies, Kwame Nkrumah University of Science and Technology, Kumasi, in partial fulfilment of the requirements for the Degree of Master of Philosophy in Pharmaceutics, February-2012