Assessment of the analgesic properties of maerua angolensis dc (capparidaceae) in animal models of pain

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Maerua angolensis is a medicinal plant used traditionally to relieve pain. Although the leaves, roots and stem barks are used, their efficacy, and safety have not been proven scientifically. This study therefore assessed the antinociceptive properties of Maerua angolensis. The antinociceptive activity on hydroethanolic extracts of the leaf, root and stem bark (30 – 300 mg/kg, p.o.) in the writhing test showed significant (P<0.0002) reduction of pain induced by acetic acid with the stem bark being more potent. Subsequently, the stem bark was extracted with petroleum ether, ethyl acetate or hydroethanol to obtain three (3) extracts which at 3 - 30 mg/kg, p.o. significantly (P<0.0006) reduced pain in both neurogenic and inflammatory phases of the formalin test in rats with the petroleum ether extract being more potent in neurogenic while ethyl acetate was more potent in inflammatory phase. Phytochemical results of the three solvent extracts shows presence of saponins, steroids, tannins, terpenoids, alkaloids, glycosides, flavonoids, oils and fats. The two most potent extracts were combined and subsequently referred to as MAE, fractionated in column to two (2) fractions F1 and F32 and purified leading to isolation of four (4) compounds C1, C2, C3 and C5 identified and characterized by 1H-NMR, GCMS and IR spectroscopy to be fatty acid and fatty acid esters namely octadecanoic acid methyl ester, bis (2-ethylhexyl) phthalate, octadecanoic acid and oleic acid methyl ester, respectively. MAE and fractions (3 – 30 mg/kg, p.o.) produced significant (P<0.05) antinociceptive effects in writhing, formalin, prostaglandin E2-induced mechanical hyperalgesia, bradykinin- and epinephrine-induced thermal hyperalgesia, tail-flick and paw withdrawal tests exhibiting both peripheral and central analgesic action. MAE and fractions reduced the number of jumps (intensity of withdrawal syndrome of morphine dependence) by mice but their effect was blocked by bicuculline and aminophylline. MAE and fractions suppress morphine withdrawal syndrome via stimulation of GABAergic and adenosinergic transmission. MAE and fractions (3 and 10 mg/kg) did not compromise the motor coordination of mice in the rotarod test, suggesting lack of central depressant effect in their antinociceptive effect. MAE and fractions effects on mechanical hyperalgesia, tactile and cold allodynia measured with Von Frey filaments and cold water in a mouse model of vincristine-induced neuropathy showed inhibition of pain suggesting their analgesic effects in cancer patients with vincristine-induced neuropathy. Theophylline, L-NAME, atropine, glibenclamide and yohimbine reversed MAE and fractions antinociception in writhing test while naloxone and ondansetron additionally reversed it in the tail-flick test. MAE and fractions inhibited capsaicin- and glutamate-induced nociception implying involvement of TRPV1 and glutamate receptors. Peripheral analgesic action of MAE and fractions involved ATP sensitive K+ channels, adenosinergic, muscarinic, α2 adrenergic and NO-cGMP paths while central action in addition involved 5-HT3 and opioid receptors. The compounds (1 – 10 mg/kg, p.o.) in writhing and wiping tests in mice reduced pain suggesting their peripheral and central analgesic action. PCPA, ondansetron, capsazepine and naloxone reversed antinociception of compounds in wiping test indicating involvement of 5-HT3, TRPV1 and opioid receptors. The compounds (3 - 30 µg/ml) reduced locomotor activity of zebrafish larvae exposed to acetic acid. Acute and sub-acute toxicity tests of MAE in rats revealed LD50 above 3000 mg/kg orally with no significant changes in body weight, relative organ weights, haematological and serum biochemical indices but significant histological changes in livers at 1000 and 3000 mg/kg MAE, showing its relative safety at therapeutic dose. Collectively, this study provides scientific data for the use of Maerua angolensis in the treatment of pains and contribute to the analgesic knowledge of this species.
A thesis submitted to the School of Graduate Studies, Kwame Nkrumah University of Science and Technology in partial fulfillment of the requirements for the award of the Degree of Doctor of Philosophy.