Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 75, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2019.105768
Keywords
Limonin; Ulcerative colitis; miR-214; p-STAT3; DSS; PTEN
Categories
Funding
- National Natural Science Foundation of China [81774096, 81873309, 81770737]
- Jiangsu Province Natural Science Foundation [BK20161610, BK20151602]
- Jiangsu Provincial Medical Youth Talent [QNRC2016642]
- Young Elite Scientists Sponsorship Program, CAST [QNRC2-B04]
- Science and technology projects of Jiangsu Province Hospital of TCM [Y18010]
- Six Talent Peaks Project in Jiangsu Province [WSN-051]
- Outstanding Youths Development Scheme of Nanfang Hospital, Southern Medical University [2015J006]
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Ulcerative colitis (UC) is a major inflammatory bowel disease (IBD) which has become a global public health problem. Limonin is a triterpenoid extracted from citrus which possesses the capacities to against inflammations and cell apoptosis. However, the efficacy and the underlying mechanisms of limonin in the treatment of UC remain unclear. In this study, we first investigated the therapeutic effects of limonin on dextran sodiumsulfate (DSS)-induced UC in vivo by examining the changes of disease activity index (DAI), the colon length, the colon histology, and cyto/chemokine levels. We found that limonin markedly reduced DAI, intestinal damages, and the levels of pro-inflammatory cytokines, such as TNF-alpha and IL-6. In vitro, limonin significantly repressed the productions of pro-inflammatory cytokines in cultured normal colonic epithelial cells. Mechanistically, we demonstrated that limonin improved the prognosis of UC mainly through downregulating p-STAT3/miR-214 levels. Collectively, our results suggested that limonin was a novel therapeutic agent and it was expected to be translated into the clinic to improve the prognosis of UC.
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