Chemopreventive Effects of Piper betle (Sirih) on High-Fat Diet-Induced and Azoxymethane-Induced Colon Cancer in Male Sprague-Dawley Rats

A high-fat diet could lead to obesity, increasing colorectal cancer risk due to dyslipidemia and chronic inflammation, while Piper betle (PB) exhibits anti-tumor, anti-inflammation, and anti-oxidant benefits. This study aimed to determine whether PB possesses chemopreventive effects on high-fat diet (HFD)-induced and azoxymethane (AOM)-induced colon cancer. Male Sprague-Dawley rats receiving either a normal diet or HFD were divided into control, PB, AOM, and AOM+PB subgroups which were then sacrificed after 24 weeks. The lipid profile, leptin, and inflammatory markers were measured from serum, and aberrant crypt foci (ACF) in the colon were detected by methylene blue staining. Cellular proliferation was identified through immunohistochemical staining of antigen Kiel 67 (Ki67) and beta-catenin. There were significant differences in serum total cholesterol, low-density lipoprotein, triglycerides, and high-density lipoprotein in the HFD compared to the normal diet group. The AOM group for normal diet and HFD exhibited significantly increased serum leptin, interleukin-6, IL-12p70, tumor necrosis factor-α, and nuclear factor-κB, with overexpression of Ki67 and beta-catenin. These changes were reversed by PB supplementation. In conclusion, PB demonstrated lipid-modifying and chemopreventive effects against HFD and AOM-induced colon cancer in rats.