Anti-nociceptive effects of an aqueous extract of the aerial parts of phyllanthus muellerianus (kuntze) exell. And its main constituent, geraniin, in rodents

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JULY, 2016.
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Phyllanthus muellerianus has been used in folk medicine for several ailments including toothache, dysmenorrhea and general body pains. However, there is little scientific data supporting its use in pain management. This study therefore evaluated the antinociceptive potential and the acute toxicological profile of the aqueous extract of the aerial parts of Phyllanthus muellerianus (PME) as well as its dominant secondary metabolite, geraniin. Acetic acid-induced abdominal writhing and formalin–induced nociception tests were used to assess the anti-nociceptive effects of PME and geraniin. The involvement of the opioidergic, adrenergic, muscarinic, adenosinergic, serotonergic and nitric oxide pathways in anti-nociception were evaluated in vivo by selective antagonism of these pathways in ICR mice. An isobolographic analysis was performed using geraniin and the conventional analgesics; morphine and diclofenac. The formalin test was used to determine whether tolerance develops to the anti-nociceptive activity of PME and geraniin after chronic administration. The effect of the agents on naloxoneprecipitated morphine withdrawal signs was also evaluated. The acute toxicological profile of the extract was also assessed after both single and multiple administrations in mice and rats respectively. Oral administration of PME (30, 100, 300 mg kg-1) and geraniin (3, 10, 30 mg kg-1) produced significant anti-nociceptive effects in all models used. The anti-nociceptive effects of both the extract and geraniin were not antagonized by all the antagonists except naloxone which reversed the anti-nociceptive effects of only geraniin. Also, isobolographic analysis of geraniin/morphine as well as geraniin/diclofenac combinations indicated synergistic effects. PME and geraniin did not produce any tolerant effects. PME and geraniin did not induce withdrawal signs and significantly produced a reduction in the number of jumps of morphine dependent mice. In the toxicological study, acute administration of high doses of the extract did not produce any lethality with the Lethal Dose 50 (LD50) of PME estimated to be above 5000 mg kg-1. There were also no significant differences found in almost all of the hematological and serum biochemical parameters as well as organ/body weight ratio. In conclusion, the aqueous extract of the aerial parts of P. muellerianus and geraniin possess anti-nociceptive effects justifying the use of the plant in traditional use as an analgesic
A thesis submitted in partial fulfillment of the requirements for the degree of Master of Philosophy in the Department of PHARMACOLOGY Faculty of Pharmacy and Pharmaceutical Sciences by Ella Anle Kasanga July.