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Cardamonin Attenuates Experimental Colitis and Associated Colorectal Cancer.

ABSTRACT: Cardamonin is a naturally occurring chalcone, majorly from the Zingiberaceae family, which includes a wide range of spices from India. Herein, we investigated the anti-inflammatory property of cardamonin using different in vitro and in vivo systems. In RAW 264.7 cells, treatment with cardamonin showed a reduced nitrous oxide production without affecting the cell viability and decreased the expression of iNOS, TNF-α, and IL-6, and inhibited NF-kB signaling which emphasizes the role of cardamonin as an anti-inflammatory molecule. In a mouse model of dextran sodium sulfate (DSS)-induced colitis, cardamonin treatment protected the mice from colitis. Subsequently, we evaluated the therapeutic potential of this chalcone in a colitis-associated colon cancer model. We performed microRNA profiling in the different groups and observed that cardamonin modulates miRNA expression, thereby inhibiting tumor formation. Together, our findings indicate that cardamonin has the potential to be considered for future therapy against colorectal cancer.

SUBMITTER: James S

PROVIDER: S-EPMC8146383 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Cardamonin Attenuates Experimental Colitis and Associated Colorectal Cancer.

James Shirley S Aparna Jayasekharan S JS Babu Anu A Paul Aswathy Mary AM Lankadasari Manendra Babu MB Athira Subha R SR Kumar Sreesha S SS Vijayan Yadu Y Namitha Narayanan N NN Mohammed Sabira S Reshmi Girijadevi G Harikumar Kuzhuvelil B KB

Biomolecules 20210429 5

Cardamonin is a naturally occurring chalcone, majorly from the Zingiberaceae family, which includes a wide range of spices from India. Herein, we investigated the anti-inflammatory property of cardamonin using different in vitro and in vivo systems. In RAW 264.7 cells, treatment with cardamonin showed a reduced nitrous oxide production without affecting the cell viability and decreased the expression of iNOS, TNF-α, and IL-6, and inhibited NF-kB signaling which emphasizes the role of cardamonin ...[more]

PMID: 33947113

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Project description:Background & aimsThe circadian clock is crucial for physiological homeostasis including gut homeostasis. Disorder of the circadian clock may contribute to many diseases including inflammatory bowel disease (IBD). However, the role and the mechanisms of circadian clock involvement in IBD still are unclear.MethodsDisorder of the circadian clock including chronic social jet lag and circadian clock gene deficiency mice (Bmal1-/-, and Per1-/-Per2-/-) were established. Dextran sulfate sodium (DSS) and/or azoxymethane were used to induce mouse models of colitis and its associated colorectal cancer. Flow cytometry, immunohistochemistry, immunofluorescence, Western blot, and reverse-transcription quantitative polymerase chain reaction were used to analyze the characteristics of immune cells and their related molecules.ResultsMice with disorders of the circadian clock including chronic social jet lag and circadian clock gene deficiency were susceptible to colitis. Functionally, regulatory B (Breg) cells highly expressing Programmed cell death 1 ligand 1 (PDL1) in intestinal intraepithelial lymphocytes (IELs) helped to alleviate the severity of colitis after DSS treatment and was dysregulated in DSS-treated Bmal1-/- mice. Notably, interleukin 33 in the intestinal microenvironment was key for Bmal1-regulated PDL1+ Breg cells and interleukin 33 was a target of Bmal1 transcriptionally. Dysregulated PDL1+ B cells induced cell death of activated CD4+ T cells in DSS-treated Bmal1-/- mice. Consequently, circadian clock disorder was characterized as decreased numbers of Breg+ PDL1+ cells in IELs and dysfunction of CD4+ T cells promoted colitis-associated colorectal cancer (CRC) in mice. In clinical samples from CRC patients, low expression of Bmal1 gene in paracancerous tissues and center area of tumor was associated closely with a poorer prognosis of CRC patients.ConclusionsOur study uncovers the importance of the circadian clock regulating PDL1+ Breg+ cells of IELs in IBD and IBD-associated CRC.

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Cardamonin Attenuates Experimental Colitis and Associated Colorectal Cancer.

Publications

Cardamonin Attenuates Experimental Colitis and Associated Colorectal Cancer.

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