The Protective Effects of Perilla frutescens Extract against Dextran Sulfate Sodium-induced Colitis in Mice and Underlying Mechanism

Abstract

The inflammatory bowel disease (IBD) which could progress to colorectal cancer (CRC) is caused by inflammation of the colon and intestine. CRC is one of the most prevalent malignancies, and accounts for the high rates of cancer-associated death. Perilla frutescens is an aromatic and edible annual herbaceous plant used as a traditional medicine and food or spice. In addition, Perilla frutescens has anti-inflammatory and immune-modulatory properties. In this study, I investigated the preventive effects of Perilla frutescens extract (PE) against dextran sulfate sodium (DSS)-induced inflammatory damage in colonic mucosa that mimics human IBD. PE was administered orally to five-week-old ICR mice for one week before and together with 3% DSS in double distilled water for 7 days. DSS-induced colitis exhibited several symptoms, such as body weight loss, colon length shortening, diarrhea, bloody stool, etc., and these were significantly attenuated by PE treatment. PE strongly reduced expression of DSS-induced inflammatory factors including cyclooxygenase-2, inducible nitric oxide synthase (iNOS) and cyclin D1 through suppression of nuclear factor-kappa B and signal transduction and activator of transcription 3 (STAT3). PE also exerted its inhibitory effects on tumor necrosis factor-alpha-induced iNOS expression, STAT3 phosphorylation and chemokine (C-X-C motif) receptor 2 expression in CCD841CoN human normal colon epithelial cells. Moreover, in murine peritoneal and bone marrow-derived macrophages, PE induced expression of heme oxygenase-1, the anti-inflammatory cytokine interleukin-10, and peroxisome proliferator-activated receptor-gamma. The above results indicate that PE has a therapeutic/preventive potential in the management of colitis and inflammation-associated colon carcinogenesis.