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ETHNOPHARMACOLOGICAL RELEVANCE Brachystegia eurycoma seed is used as dietary condiment and as part of recipes for treating colorectal disorders, while laboratory studies have established that it contains crude fiber and polyphenols which are important in cancer prevention. AIM OF THE STUDY To establish the efficacy of a Nigerian diet in colon cancer prevention, a study was conducted to evaluate dietary inclusion of Brachystegia eurycoma seed in experimental colon carcinogenesis. METHODS Rats undergoing intra-rectal instillations of N-Methyl-N-nitrosourea (MNU) were fed B. eurycoma included diets at 0%, 2.5%, 5% and 10% for a period of ten (10) weeks following which they were sacrificed; blood and tissues were monitored for biochemical, histological and immunohistochemical parameters. RESULTS Brachystegia eurycoma significantly (P < 0.05) prevented MNU-induced elevation of malondialdehyde and carcinoembryonic antigen (CEA) as well as reduced activities of catalase and superoxide dismutase. The colon showed deep mucosal ulceration with moderate inter-glandular inflammation in the MNU control group, but only mild or no inflammation was observed in the colon of the MNU groups fed experimental diets. Similarly, colon immunohistochemistry assay showed that the dietary inclusion significantly prevented MNU-induced damage to mismatch repair gene (MutL homolog1). Positive relationship existed between fiber content of B. eurycoma seeds and MutL homolog1 protein expression while that between polyphenol/flavonoids contents of diets and CEA was negative. CONCLUSION These data suggest that both dietary fiber and polyphenol/flavonoids contribute synergistically or additively to the potential preventive effect of B. eurycoma seeds in colon carcinogenesis, presumably through mechanisms that involve limiting the extent of oxidative stress and preventing or delaying the onset of pro-carcinogenic inflammatory processes.