Nerolidol Mitigates Colonic Inflammation: An Experimental Study Using both In Vivo and In Vitro Models.

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

Original Publication: Basel, Switzerland : MDPI Publishing

Anti-Inflammatory Agents* ; Phytotherapy*; Inflammatory Bowel Diseases/*drug therapy ; Inflammatory Bowel Diseases/*metabolism ; Phytochemicals/*administration & dosage ; Phytochemicals/*pharmacology ; Sesquiterpenes/*administration & dosage ; Sesquiterpenes/*pharmacology; Administration, Oral ; Animals ; Antioxidants/metabolism ; Colon/metabolism ; Colon/pathology ; Cytokines/metabolism ; Disease Models, Animal ; HT29 Cells ; Humans ; Inflammation Mediators/metabolism ; Inflammatory Bowel Diseases/pathology ; Macrophages ; Male ; Mice, Inbred C57BL ; NF-E2-Related Factor 2/metabolism ; Neutrophils ; Peroxidase/metabolism ; Phytochemicals/isolation & purification ; Sesquiterpenes/isolation & purification

Nerolidol (NED) is a naturally occurring sesquiterpene alcohol present in various plants with potent anti-inflammatory effects. In the current study, we investigated NED as a putative anti-inflammatory compound in an experimental model of colonic inflammation. C57BL/6J male black mice (C57BL/6J) were administered 3% dextran sodium sulfate (DSS) in drinking water for 7 days to induce colitis. Six groups received either vehicle alone or DSS alone or DSS with oral NED (50, 100, and 150 mg/kg body weight/day by oral gavage) or DSS with sulfasalazine. Disease activity index (DAI), colonic histology, and biochemical parameters were measured. TNF-α-treated HT-29 cells were used as in vitro model of colonic inflammation to study NED (25 µM and 50 µM). NED significantly decreased the DAI and reduced the inflammation-associated changes in colon length as well as macroscopic and microscopic architecture of the colon. Changes in tissue Myeloperoxidase (MPO) concentrations, neutrophil and macrophage mRNA expression (CXCL2 and CCL2), and proinflammatory cytokine content (IL-1β, IL-6, and TNF-α) both at the protein and mRNA level were significantly reduced by NED. The increase in content of the proinflammatory enzymes, COX-2 and iNOS induced by DSS were also significantly inhibited by NED along with tissue nitrate levels. NED promoted Nrf2 nuclear translocation dose dependently. NED significantly increased antioxidant enzymes activity (Superoxide dismutase (SOD) and Catalase (CAT)), Hemeoxygenase-1 (HO-1), and SOD3 mRNA levels. NED treatment in TNF-α-challenged HT-29 cells significantly decreased proinflammatory chemokines (CXCL1, IL-8, CCL2) and COX-2 mRNA levels. NED supplementation attenuates colon inflammation through its potent antioxidant and anti-inflammatory activity both in in vivo and in vitro models of colonic inflammation.

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grant # 31M384. United Arab Emirates University

Keywords: bioactive compounds; colitis; inflammatory bowel disease; inflammatory molecular mechanisms; nerolidol; phytochemical

0 (Anti-Inflammatory Agents)
0 (Antioxidants)
0 (Cytokines)
0 (Inflammation Mediators)
0 (NF-E2-Related Factor 2)
0 (Nfe2l2 protein, mouse)
0 (Phytochemicals)
0 (Sesquiterpenes)
EC 1.11.1.7 (Peroxidase)
QR6IP857S6 (nerolidol)

Date Created: 20200712 Date Completed: 20210311 Latest Revision: 20210311

20231215

PMC7400891

10.3390/nu12072032

32650602