期刊
PHARMACOLOGICAL RESEARCH
卷 169, 期 -, 页码 -出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2021.105613
关键词
Didymin; Ulcerative colitis; Macrophage polarization; Fatty acid oxidation
资金
- Program of the National Natural Science Foundation of China [81903885, 82073719]
- Program of the Jiangsu Shuang Chuang Team [20182036]
- Key Research Projects of Jiangsu Higher Education [18KJA360010]
- Jiangsu Postgraduate Research & Practice Innovation Program [KYCX20_1559]
Our study demonstrates that didymin can alleviate clinical symptoms of colitis in mice by modulating macrophage phenotypes. Mechanistic studies reveal that didymin induces the conversion of pro-inflammatory M1-like macrophages to anti-inflammatory M2-like macrophages through enhancing fatty acid oxidation.
Inflammatory response by different polarized macrophages has a critical role in a variety of immunological pathophysiology, such as ulcerative colitis (UC). Herein, targeting the paradigm of macrophage phenotypes by small molecular modulators may influence the disease status. In the present study, we firstly demonstrated that didymin, one of the most abundant flavonoid constituents present in the citrus fruits such as oranges and lemons, remarkably attenuated the clinical symptoms of acute and chronic colitis in mice. Mechanistic studies showed that didymin converted pro-inflammatory M1-like to anti-inflammatory M2-like macrophage phenotype, but did not alter the polarization of M2-like macrophages. Metabolic tracing studies revealed that didymin strengthened fatty acid oxidation rather than glycolysis by inducing Hadhb expression. More importantly, in vivo studies verified that promotion of Hadhb expression resulted in the conversion of M1- toward M2-like macrophages and eventually alleviated colitis. Our data highlights the potential of macrophage paradigm in UC inflammation and put forth the stage for considering didymin as a metabolism regulator in reprogramming macrophage polarization, which may serve as a promising therapeutic approach for treatment of inflammation-associated disorders.
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