Evaluation of safety and efficacy of Brazilian brown propolis from <i>Araucaria sp</i> . in preventing colon cancer

Brazilian propolis produced by honeybees have been widely studied, but few data exist regarding the safety and pharmacological potential of this natural product. The aim of the present study was to examine the toxicity, genotoxicity, and chemoprevention effects attributed to exposure to the brown propolis hydroalcoholic extract (BPHE) of <i>Araucaria sp</i>. Acute oral toxicity test was conducted using Wistar Hannover rats, demonstrating that the highest dose tested (2,000 mg/kg b.w.) produced no apparent adverse effects or lethality. The micronucleus (MN) genotoxicity test was conducted using peripheral blood from Swiss mice, which also noted that BPHE did not induce significant chromosomal damage. It is of interest that BPHE at a dose of 12 mg/kg b.w. exhibited antigenotoxic effects against the doxorubicin (DXR)-induced damage. However, BPHE did not influence the depletion of reduced glutathione induced by DXR in mice. It is noteworthy that BPHE exerted chemopreventive effects at doses 6, 12, and 24 mg/kg b.w. The determination of this effect of BPHE on colon carcinogenesis was examined using aberrant crypt foci (ACF) as evidenced by histological analysis. The colons of animals treated with BPHE (12 mg/kg b.w.) exhibited a significant reduction in staining for proliferating cell nuclear antigen (PCNA) and cyclooxygenase-2 (COX-2) protein following 1,2-dimethylhydrazine (DMH)-and BPHE combined treatments. Hence, it is conceivable that the anti-inflammatory activity of the chemical constituents of BPHE are involved in its chemopreventive action against colon carcinogenesis as evidenced from ACF assay. Therefore, BHPE was found to be a safe product, without any apparent significant acute adverse risk. Further, the extract exhibited antigenotoxic and anticarcinogenic activities which may be considered for beneficial uses in colon carcinogenesis.