Anti-Inflammatory, anagelsic and toxicity studies on ethanolic, aqueous and petroleum Ether extracts of stem bark of Trichilia Monadelpha (Thonn) JJ De Wilde

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Trichilia monadelpha (Thonn) JJ De Wilde (fam. Meliaceae) is a medium-sized tree that grows in the tropical rain forest. In Ghana, the aqueous extract of the stem bark of the plant is used to treat various diseases. This project investigated the anti-inflammatory (acute and chronic) and analgesic activities of the aqueous (TWE), alcoholic (TAE) and petroleum ether (TPEE) extracts of stem bark of the plant. Chick carrageenan induced foot edema model was used to test the effect of the extracts on acute inflammation and adjuvant induced arthritic model was used to test the effect of the extracts on chronic inflammation. To induce acute inflammation, 0.1 ml of 1% carrageenan was injected into the right footpads of 7-day-old chicks (n = 5). Extracts (10-300 mg/kg, p.o.) were given to chicks 1 hour after carrageenan challenge. Diclofenac (10-100 mg/kg i.p.) and dexamethasone (0.1-1.0 mg/kg i.p.) were used as reference drugs. Chronic inflammation was induced by inoculating rats (120-320 g) with 0.1 ml of 3 mg/ml of complete Freund’s adjuvant (CFA). Rats (n = 5) were treated with the extracts and the reference drugs dexamethasone, diclofenac and methotrexate 10 days after CFA inoculation. Analgesic effects of the extracts were evaluated by using the formalin test in mice. In the formalin test, mice were pretreated with the extracts 1 hour or the reference drugs 30 minutes before injection of 10 µl of 4% formalin into the ventral surface of the right hind paw. Morphine and diclofenac were used as reference drugs. Sub acute toxicity test in rats was employed to assess the safety of the aqueous extract. From the results, diclofenac and dexamethasone significantly inhibited carrageenan-induced foot edema in 7-day-old chicks with maximal percentage inhibitions of 71.85±1.53 at 1.0 mg/kg for dexamethasone and 62.92±2.03 at 100 mg/kg for diclofenac. Similarly, TPEE and TWE inhibited the paw edema significantly with maximum percentage inhibitions of 63.83±1.28 at 300 mg/kg for TPEE and 57.79±3.92 at 300 mg/kg for TWE. On the contrary, TAE had no significant effect on the carrageenan-induced foot edema. In the adjuvant-induced arthritis, the extracts and the reference drugs decreased the joint thickness. Maximal percentage inhibitions were 85.75±2.96 at 1.0 mg/kg, 80.28±5.79 at 100 mg/kg, 74.68±3.03 at 1.0 mg/kg, 62.81±2.56 300 mg/kg, 64.41±5.56 at 300 mg/kg and 57.40±8.57 at 300 mg/kg for dexamethasone, diclofenac, methotrexate, TPEE, TWE and TAE respectively. In the formalin test, TWE, TPEE and morphine significantly reduced the pain scores in both phases. Diclofenac was more effective in phase 2 than phase 1. TAE did not show significant effect on phase 2. The sub acute toxicity test did not give any evidence of adverse effect on the blood, kidney, heart, spleen, liver or stomach of the rats. All together, the observations of these studies showed that the stem bark extracts of Trichilia monadelpha have anti-inflammatory as well as analgesic effects and oral administration of aqueous extracts for two weeks gave no evidence of toxicity.
A thesis submitted in fulfillment of the requirements for the degree of Master of Philosophy In the Department of Pharmacology.