Hesperetin Alleviated Experimental Colitis via Regulating Ferroptosis and Gut Microbiota.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: MDPI Publishing Country of Publication: Switzerland NLM ID: 101521595 Publication Model: Electronic Cited Medium: Internet ISSN: 2072-6643 (Electronic) Linking ISSN: 20726643 NLM ISO Abbreviation: Nutrients Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI Publishing
    • Subject Terms:
      Hesperidin*/pharmacology ; Ferroptosis*/drug effects ; Gastrointestinal Microbiome*/drug effects ; Dextran Sulfate* ; Disease Models, Animal*; Animals ; Mice ; Male ; Colitis, Ulcerative/drug therapy ; Colitis/drug therapy ; Colitis/chemically induced ; Mice, Inbred C57BL ; Colon/drug effects ; Colon/pathology ; Colon/metabolism ; Tumor Necrosis Factor-alpha/blood ; Tumor Necrosis Factor-alpha/metabolism ; Cyclooxygenase 2/metabolism ; Molecular Docking Simulation ; Humans ; Interleukin-6/blood ; Interleukin-6/metabolism ; Network Pharmacology ; Lipid Peroxidation/drug effects ; Dietary Supplements ; Phospholipid Hydroperoxide Glutathione Peroxidase
    • 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.
    • References:
      J Crohns Colitis. 2023 Dec 23;:. (PMID: 38141256)
      Nucleic Acids Res. 2000 Jan 1;28(1):235-42. (PMID: 10592235)
      Genome Res. 2003 Nov;13(11):2498-504. (PMID: 14597658)
      J Biochem Mol Toxicol. 2021 May;35(5):e22730. (PMID: 33522063)
      BMC Complement Med Ther. 2024 Jun 10;24(1):226. (PMID: 38858650)
      Front Pharmacol. 2020 Jan 22;10:1553. (PMID: 32038241)
      J Gastroenterol. 2023 Aug;58(8):751-765. (PMID: 37351647)
      Int J Mol Sci. 2013 Dec 19;15(1):15-28. (PMID: 24451125)
      Eur J Pharmacol. 2019 Aug 15;857:172456. (PMID: 31220438)
      Sci Total Environ. 2023 Aug 20;887:164050. (PMID: 37178843)
      Immunopharmacol Immunotoxicol. 2024 Apr;46(2):240-254. (PMID: 38156770)
      Gut Microbes. 2023 Jan-Dec;15(1):2192478. (PMID: 36951545)
      Phytother Res. 2024 Mar;38(3):1478-1493. (PMID: 38234096)
      Imeta. 2022 Mar 16;1(2):e12. (PMID: 38868573)
      Int J Gen Med. 2023 Jun 27;16:2693-2705. (PMID: 37398511)
      J Crohns Colitis. 2023 Apr 3;17(3):352-360. (PMID: 36125105)
      J Ethnopharmacol. 2024 Jul 15;329:118162. (PMID: 38588989)
      Inflamm Bowel Dis. 2022 Nov 2;28(11):1647-1657. (PMID: 35134912)
      Inflamm Bowel Dis. 2012 Oct;18(10):1799-808. (PMID: 22170749)
      Microbiol Res. 2024 May;282:127660. (PMID: 38442454)
      Nucleic Acids Res. 2023 Jan 6;51(D1):D1373-D1380. (PMID: 36305812)
      Crit Rev Food Sci Nutr. 2024;64(19):6834-6849. (PMID: 36803092)
      BMC Bioinformatics. 2014 Aug 29;15:293. (PMID: 25176396)
      Front Immunol. 2022 Sep 14;13:988849. (PMID: 36189293)
      BMC Gastroenterol. 2023 Mar 12;23(1):71. (PMID: 36907848)
      J Inflamm Res. 2023 May 11;16:2023-2039. (PMID: 37197438)
      Int J Mol Sci. 2018 Oct 07;19(10):. (PMID: 30301267)
      Cell Death Dis. 2020 Feb 3;11(2):86. (PMID: 32015337)
      Biotech Histochem. 2019 Apr;94(3):151-158. (PMID: 30383440)
      Nutrients. 2023 Jan 09;15(2):. (PMID: 36678190)
      J Hazard Mater. 2023 Oct 5;459:132057. (PMID: 37467611)
      World J Gastroenterol. 2023 Feb 28;29(8):1330-1343. (PMID: 36925457)
      Curr Med Res Opin. 2023 May;39(5):681-689. (PMID: 36951899)
      Nucleic Acids Res. 2019 Jan 8;47(D1):D976-D982. (PMID: 30365030)
      Methods Mol Biol. 2016;1418:93-110. (PMID: 27008011)
      Nutrients. 2022 Feb 10;14(4):. (PMID: 35215394)
      Front Cell Infect Microbiol. 2022 Oct 04;12:1015890. (PMID: 36268225)
      Nucleic Acids Res. 2023 Jan 6;51(D1):D638-D646. (PMID: 36370105)
      Inflamm Bowel Dis. 2023 Oct 3;29(10):1613-1621. (PMID: 37221272)
      Phytother Res. 2001 Dec;15(8):655-69. (PMID: 11746857)
      Integr Cancer Ther. 2022 Jan-Dec;21:15347354221086900. (PMID: 35297710)
      Phytother Res. 2023 May;37(5):1787-1805. (PMID: 36437582)
      J Agric Food Chem. 2023 Dec 20;71(50):20073-20091. (PMID: 38064669)
      Front Pharmacol. 2023 Jan 13;14:1095366. (PMID: 36713828)
      Antioxidants (Basel). 2024 Mar 10;13(3):. (PMID: 38539867)
      Nucleic Acids Res. 2019 Jul 2;47(W1):W357-W364. (PMID: 31106366)
      Clin Exp Med. 2023 Sep;23(5):1763-1772. (PMID: 36344781)
      Int J Mol Sci. 2022 Dec 16;23(24):. (PMID: 36555694)
      Dig Liver Dis. 2021 Oct;53(10):1276-1285. (PMID: 33640301)
      Life (Basel). 2023 Apr 11;13(4):. (PMID: 37109513)
      J Cheminform. 2011 Oct 07;3:33. (PMID: 21982300)
      Cell Death Dis. 2020 Feb 24;11(2):144. (PMID: 32094346)
      Evid Based Complement Alternat Med. 2015;2015:957031. (PMID: 26221182)
      Free Radic Biol Med. 2024 Mar;214:219-235. (PMID: 38367927)
      Toxicol Sci. 2023 Sep 28;195(2):155-168. (PMID: 37486259)
      Life Sci. 2024 Apr 1;342:122533. (PMID: 38428570)
      Nutrients. 2024 Mar 24;16(7):. (PMID: 38612971)
      Phytomedicine. 2024 Jun;128:155523. (PMID: 38489893)
      Nucleic Acids Res. 2022 Jul 5;50(W1):W159-W164. (PMID: 35609983)
      Pharmacol Res. 2024 Apr;202:107128. (PMID: 38438089)
      Nat Rev Gastroenterol Hepatol. 2021 Jan;18(1):56-66. (PMID: 33033392)
      J Agric Food Chem. 2015 Sep 16;63(36):7952-7. (PMID: 26306898)
      Lancet Gastroenterol Hepatol. 2023 May;8(5):391. (PMID: 37030297)
      J Agric Food Chem. 2019 Sep 4;67(35):9812-9819. (PMID: 31392887)
      Cell. 2012 May 25;149(5):1060-72. (PMID: 22632970)
      Comput Struct Biotechnol J. 2021 May 11;19:2960-2967. (PMID: 34136095)
      BMC Complement Altern Med. 2015 Jul 30;15:256. (PMID: 26220068)
    • Grant Information:
      SYS202202 Shandong Provincial Laboratory Project; JNL-2022001A Research Project of Jinan Microecological Biomedicine Shandong Laboratory; 2022ZFJH003 the Fundamental Research Funds for the Central Universities
    • Contributed Indexing:
      Keywords: ferroptosis; hesperetin; ulcerative colitis
    • Accession Number:
      E750O06Y6O (Hesperidin)
      Q9Q3D557F1 (hesperetin)
      9042-14-2 (Dextran Sulfate)
      0 (Tumor Necrosis Factor-alpha)
      EC 1.14.99.1 (Cyclooxygenase 2)
      EC 1.14.99.- (Ptgs2 protein, mouse)
      EC 1.11.1.9 (glutathione peroxidase 4, mouse)
      0 (Interleukin-6)
      EC 1.11.1.12 (Phospholipid Hydroperoxide Glutathione Peroxidase)
    • Publication Date:
      Date Created: 20240727 Date Completed: 20240728 Latest Revision: 20240729
    • Publication Date:
      20240729
    • Accession Number:
      PMC11279615
    • Accession Number:
      10.3390/nu16142343
    • Accession Number:
      39064786