Antiinflammatory Effect of Mahkota Dewa (Phaleria macrocarpa (Scheff.) Boerl.) Leaves Extract on Colon Carcinogenesis Induced by Azoxymethane and Dextran Sodium Sulphate: Focus on the iNOS, Î²-catenin and COX-2. expressions.
Colorectal cancer is a malignant tumor caused by excessive growth derived from the colon wall. Chemical carcinogens, azoxymethane (AOM)+dextran sodium sulphate (DSS) are known to cause the formation of adenoma in the colon characterized by increased expressions of iNOS, Î²-catenin and COX-2. Ethanol extract of mahkota dewa leaves are known to have anticancer effects, but until now the mechanism has not been fully understood. This study was aimed to determine the effect of Â Â Ethanol extracts of mahkota dewa leaves (MD) on colon carcinogenesis induced by AOM-DSS. Balb/c mice were randomly divided into 6 groups of untreated control; AOM + mahkota dewa 25 mg + DSS; AOM + mahkota dewa 50 mg + DSS; AOM + aspirin 0,21 mg + DSS (positive control 1); AOM+ aspirin 0,84 mg + DSS (positive control 2). MD/aspirin was administered daily per oral for 7 days, starting 1 week after AOM induction, while DSS 1% was given through drinking water daily for 7 days ad libitum. Twenty weeks post AOM administration, mice were sacrificed, colons were taken and analyzed histopathologically. Expression of iNOS, Î²-catenin and COX-2 were analyzed using immunohistochemistry. Tissue damage induced by AOM + DSS goblet cells were in the form of inflammation (inflammation score 192). Ethanol extracts of mahkota dewa dose 25 mg and 50 mg were shown significant to reduce tissue damage induced by chemical carcinogens AOM+DSS (inflammation score decreased to 45 and 58; p < 0,05). Ethanol extracts of mahkota dewa leaves suppressed the expression of iNOS, Î²-catenin and COX-2 significantly vs AOM+DSS at all doses, except for Ethanol extracts of mahkota dewa dose 50 mg, which was unable to suppress the expression of COX-2. Ethanol extracts of mahkota dewa leaves can reduce inflammatory process induced by chemical carcinogens AOM+DSS. This effect is due to the inhibitory effect of mahkota dewa leaves extract to the iNOS, Î²-cateninÂ and COX-2 expressions.
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