期刊
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
卷 69, 期 50, 页码 15240-15251出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.1c06292
关键词
PPAR gamma; MKRN1; hyperoside; colitis; Th17/Treg
资金
- National Natural Scientific Funds [81770014, 81991523, 82000014]
- National Key Research and Development Program Project [2018YFC1705900]
- Natural Science Foundation of Nanjing University of Chinese Medicine [NZY82000014]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
The study demonstrates that HYP treatment effectively alleviates ulcerative colitis in mice by reducing pathological scores, suppressing colonic inflammation, and balancing Th17/Treg response. Mechanistically, HYP enhances PPAR γ signaling by inhibiting MKRN1, promoting Treg differentiation and suppressing Th17 cell development.
Hyperoside (HYP), a naturally occurring flavonoid compound, exerts multiple biological functions including myocardial protection, antiredox, and anti-inflammatory activities. However, the role of HYP on inflammatory bowel disease (IBD) and the underlying mechanism need to be further established. Here, we show that HYP treatment profoundly alleviated dextran sulfate sodium-induced ulcerative colitis in mice, characterized by reduced pathological scores, preserved tissue integrity, suppressed colonic inflammation, and balanced Th17/Treg response. Mechanistically, HYP was shown to restrain the expression of the E3 ubiquitin ligase, makorin ring finger protein 1 (MKRN1), which in turn promoted the ubiquitination and proteasomal degradation of peroxisome proliferator-activated receptor gamma (PPAR gamma), an essential regulator of Th17 and Treg differentiation. Consequently, HYP treatment enhanced PPAR gamma. signaling and hence promoted Treg differentiation while suppressing Th17 cell development during colitis. Thus, our data indicate that HYP acts through the MKRN1/PPAR gamma axis to modulate the Th17/Treg axis and thereby confers protection against experimental colitis. The findings extend our understanding about HYP action and may provide a potential therapeutic target for IBD.
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