Limonin modulated immune and inflammatory responses to suppress colorectal adenocarcinoma in mice model.

Abstract

Inflammation and compromised immune responses often increase colorectal cancer (CRC) risk. The immune-modulating effects of limonin on carcinogen/inflammation-induced colorectal cancer (CRC) were studied in mice. 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 developments were monitored via macroscopic, histopathological, ELISA, and mRNA expression analyses. 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 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 them to normal levels suggesting reinstatement to normal colon conditions. Limonin apparently mitigated CRC development, by ameliorating adaptive immune responses (CD8, CD4, and CD19), reducing inflammation (serum prostaglandin E2; TNF-α, innate immune responses) and oxidative stress, and enhancing the endogenous anti-oxidation defense reactions (GSH) in CRC-induced mice.

• Authors: Nur Iliyani Mohd Ishak, Suhaila Mohamed, Iffah Nadhira Madzuki, Noordin Mohamed Mustapha, Norhaizan Mohd Esa
• Journal: Naunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 394 Issue 9 Pg. 1907-1915 (09 2021) ISSN: 1432-1912 [Electronic] Germany
• PMID: 34009457 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Chemical References

• Antioxidants
• Limonins
• Dextran Sulfate
• limonin
• Azoxymethane

Topics

• Adenocarcinoma (drug therapy, pathology)
• Animals
• Antioxidants (metabolism)
• Azoxymethane
• Colorectal Neoplasms (drug therapy, pathology)
• Dextran Sulfate
• Disease Models, Animal
• Inflammation (drug therapy, pathology)
• Limonins (pharmacology)
• Male
• Mice
• Mice, Inbred BALB C
• Oxidative Stress (drug effects)