Limonin Modulated Immune and Inflammatory Responses to Suppress Colorectal Adenocarcinoma in Mice Model

Abstract Purpose. Inflammation and compromised immune responses often increases colorectal cancer (CRC) risk. The immune-modulating effects of limonin on carcinogen/inflammation-induced colorectal cancer (CRC) were studied in mice. Methods: Male Balb/c mice were randomly assorted into three groups (n=6): healthy control, non-treated CRC-induced (azoxymethane/dextran-sulfate-sodium AOM/DSS) control, and CRC-induced+50 mg limonin /kg body-weight. The CRC development were monitored via macroscopic, histopathological, ELISA and mRNA expression analysis. Results: Limonin downregulated inflammation (TNF-α, tumor necrosis factor-α), enhanced the adaptive immune responses (CD8, CD4, and CD19), and upregulated antioxidant defense (Nrf2, SOD2) mRNA expressions. Limonin reduced serum malondialdehyde (MDA, lipid peroxidation biomarker), prostaglandin-E2 and histopathology inflammation scores, while increasing reduced-glutathione (GSH) in the CRC-induced mice. Limonin significantly (p<0.05) increased T cells (CD4 and CD8) and B cells (CD19) in spleen tissues. The CD335 (natural killer cells) were increased in the CRC-induced mice and limonin treatment restored it to normal levels suggesting reinstatement to normal colon conditions.Conclusion: Limonin apparently mitigated CRC development, by ameliorating adaptive immune responses (CD8, CD4, and CD19), reducing inflammation (serum prostaglandin-E2; TNF-α, innate immune responses), oxidative stress and enhancing the endogenous anti-oxidation defense reactions (GSH) in the CRC-induced mice.