{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T23:30:18Z","timestamp":1792020618836,"version":"4.4.0"},"reference-count":41,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T00:00:00Z","timestamp":1736467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hunan Natural Science Foundation Project","award":["2021JJ31154"],"award-info":[{"award-number":["2021JJ31154"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Previous research has consistently shown that high-fat diet (HFD) consumption can lead to the development of colonic inflammation. Neohesperidin (NHP), a naturally occurring flavanone glycoside in citrus fruits, has anti-inflammatory properties. However, the efficacy and mechanism of NHP in countering prolonged HFD-induced inflammation remains unclear. In this study, rats on HFD were intragastrically administered (i.g.) with NHP for 12 consecutive weeks. Results indicate that this natural compound is effective in reducing colorectal inflammation at doses of 40\u201380 mg\/kg body weight (BW) by i.g. administration, with significant decreases in inflammation markers such as TNF-\u03b1 and IL-1\u03b2 levels. It also improved intestinal mucosal tissue integrity and reduced HFD-stimulated colorectal inflammation via the JAK2\/STAT3 pathway. Furthermore, intestinal microbiota sequencing results show that NHP intervention significantly downregulated the Firmicutes\/Bacteroidetes ratio. This ratio is closely related to the preventive role in the context of glycolipid metabolism disorder. Compared with fecal cultures of rats from the HFD group, after 48 h in vitro fermentation, those from the NHP group had distinct microbiota composition and notably higher concentrations of SCFAs. Collectively, these observations suggest that 80 mg\/kg BW NHP possesses biological activities in downregulating HFD-induced colorectal inflammation by regulating intestinal flora and promoting SCFAs formation.<\/jats:p>","DOI":"10.3390\/ijms26020534","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T03:48:11Z","timestamp":1736480891000},"page":"534","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Neohesperidin Mitigates High-Fat-Diet-Induced Colitis In Vivo by Modulating Gut Microbiota and Enhancing SCFAs Synthesis"],"prefix":"10.3390","volume":"26","author":[{"given":"Kun","family":"Lu","sequence":"first","affiliation":[{"name":"National Engineering Laboratory for Rice and By-Products Processing, Food Science and Engineering College, Central South University of Forestry and Technology, Changsha 410004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijie","family":"Shan","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Rice and By-Products Processing, Food Science and Engineering College, Central South University of Forestry and Technology, Changsha 410004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2140-9510","authenticated-orcid":false,"given":"Yanling","family":"Zeng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cultivation and Protection for Non-Wood Forest Trees, Ministry of Education, Central South University of Forestry and Technology, Changsha 410004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guliang","family":"Yang","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Rice and By-Products Processing, Food Science and Engineering College, Central South University of Forestry and Technology, Changsha 410004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1080\/15548627.2023.2254191","article-title":"Dysfunction of autophagy in high-fat diet-induced non-alcoholic fatty liver disease","volume":"20","author":"Ren","year":"2024","journal-title":"Autophagy"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1021\/acs.jafc.3c02909","article-title":"High Fat Diet and High Sucrose Intake Divergently Induce Dysregulation of Glucose Homeostasis through Distinct Gut Microbiota-Derived Bile Acid Metabolism in Mice","volume":"72","author":"He","year":"2024","journal-title":"J. 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