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Open AccessArticle
Hesperetin Alleviated Experimental Colitis via Regulating Ferroptosis and Gut Microbiota
by
Jinzhi Wang
Jinzhi Wang 1,†,
Yuanyuan Yao
Yuanyuan Yao 1,†,
Ting Yao
Ting Yao 1,
Qingmiao Shi
Qingmiao Shi 1,
Yifan Zeng
Yifan Zeng 1 and
Lanjuan Li
Lanjuan Li 1,2,*
1
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China
2
Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250000, China
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Nutrients 2024, 16(14), 2343; https://doi.org/10.3390/nu16142343 (registering DOI)
Submission received: 2 June 2024
/
Revised: 28 June 2024
/
Accepted: 16 July 2024
/
Published: 19 July 2024
Abstract
Hesperetin (HT) is a type of citrus flavonoid with various pharmacological activities, including anti-tumor, anti-inflammation, antioxidant, and neuroprotective properties. However, the role and mechanism of HT in ulcerative colitis (UC) have been rarely studied. Our study aimed to uncover the beneficial effects of HT and its detailed mechanism in UC. Experimental colitis was induced by 2.5% dextran sodium sulfate (DSS) for seven days. HT ameliorated DSS-induced colitis in mice, showing marked improvement in weight loss, colon length, colonic pathological severity, and the levels of TNFα and IL6 in serum. A combination of informatics, network pharmacology, and molecular docking identified eight key targets and multi-pathways influenced by HT in UC. As a highlight, the experimental validation demonstrated that PTGS2, a marker of ferroptosis, along with other indicators of ferroptosis (such as ACSL4, Gpx4, and lipid peroxidation), were regulated by HT in vivo and in vitro. Additionally, the supplement of HT increased the diversity of gut microbiota, decreased the relative abundance of Proteobacteria and Gammaproteobacteria, and restored beneficial bacteria (Lachnospiraceae_NK4A136_group and Prevotellaceae_UCG-001). In conclusion, HT is an effective nutritional supplement against experimental colitis by suppressing ferroptosis and modulating gut microbiota.
Share and Cite
MDPI and ACS Style
Wang, J.; Yao, Y.; Yao, T.; Shi, Q.; Zeng, Y.; Li, L.
Hesperetin Alleviated Experimental Colitis via Regulating Ferroptosis and Gut Microbiota. Nutrients 2024, 16, 2343.
https://doi.org/10.3390/nu16142343
AMA Style
Wang J, Yao Y, Yao T, Shi Q, Zeng Y, Li L.
Hesperetin Alleviated Experimental Colitis via Regulating Ferroptosis and Gut Microbiota. Nutrients. 2024; 16(14):2343.
https://doi.org/10.3390/nu16142343
Chicago/Turabian Style
Wang, Jinzhi, Yuanyuan Yao, Ting Yao, Qingmiao Shi, Yifan Zeng, and Lanjuan Li.
2024. "Hesperetin Alleviated Experimental Colitis via Regulating Ferroptosis and Gut Microbiota" Nutrients 16, no. 14: 2343.
https://doi.org/10.3390/nu16142343
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