SOURCE:

Faculty: Pharmaceutical Sciences
Department: Pharmacology And Toxicology

CONTRIBUTORS:

Umeh, V. N.
Akah, P. A.
Ilodigwe, E. E.

ABSTRACT:

Aqueous seed extract of Persea americana (ASEPA) has been used to treat peptic ulcer disease in folkloric medicine, but its efficacy has not been validated. The present study was carried out to evaluate the anti-ulcer activity of ASEPA and its n-hexane and water fractions in rats. Dried and milled seeds of P. americana was soaked in distilled water (25 oC) for 24 h, filtered and freeze-dried. The extract was fractionated with n-hexane and residue was the water fraction. Acute toxicity study (LD50) and phytochemical screening were carried out. The ulcer-protective effects of ASEPA and fractions were tested (250 and 500 mg/kg for 14 days per oral) on ulcer models induced by ethanol, aspirin, stress and pyloric ligation, while the ulcer-healing effects were tested on ulcer models induced by ethanol, aspirin and stress. Cimetidine (150 mg/kg) and distilled water (10 ml/kg) served as the standard drug and negative control respectively. Outcome measures were ulcer index, percentage healing of ulcer, gastric acid volume, pH, free acidity and total acidity. Effects on biochemical parameters and gastrointestinal motility were also investigated. Histopathological examinations of the stomach, antimicrobial activity of ASEPA and fractions and their effect on isolated guinea pig ileum were carried out. For identification of the major compound and structure elucidation, HPLC and GC-MS analysis of the extract and fractions were carried out. Data were analyzed using one-way ANOVA and P<0.05 was considered as statistically significant. The estimated oral median lethal dose (LD50) was higher than 5000 mg/kg for ASEPA. Secondary metabolites such as flavonoids, tannins, and saponins were present. ASEPA and fractions conferred dose-dependent ulcer-protective and ulcer-healing effects on the ulcer models used. For the ulcer-protective study, oral treatment with ASEPA and fractions at 500 mg/kg reduced significantly (p<0.05) ulcer indices in all the ulcer models. These reductions were comparable with that of the reference drug and in some cases (especially with n-hexane fraction) being more effective. It was also observed that ASEPA and fractions (500 mg/kg) demonstrated higher percentage healing effect than cimetidine (150 mg/kg) in the ethanol-induced ulcer model. There were dose-dependent inhibitory effect on E.coli, P. aeruginosa, K. pneumonia, S. aureus, S. typhi, C. albican and A. niger but water fraction seems to have the highest anti-bacterial effect considering its low minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values against most of the tested micro-organisms. The dose-dependent and none dose-dependent spasmolytic effect of ASEPA and fractions on GIT transit and on isolated guinea pig ileum respectively confirmed the ulcer-healing and ulcer-protective effects of ASEPA and fractions. The histopathology result also confirmed their cytoprotective property. The ability of ASEPA and fractions to reduce and increase significantly (p<0.05) malondialdhyde and catalase levels respectively as was observed, may have also contributed to their ulcer-healing and ulcer-protective effects. HPLC analysis revealed Absciscic acid as the major compound while GC-MS analysis elucidated structures of 24 monosaturated fatty acids. These compounds may in part be responsible for the pharmacological effects of P. americana seeds.