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

Vishnu Raj,Shreesh K Ojha,Saeeda Almarzooqi,Sanjana Chandran,Balaji Venkataraman,Samir Attoub,Thomas E Adrian,Sandeep B Subramanya

doi:10.3390/nu12072032

Vishnu Raj, Shreesh K Ojha + Show 6 more

Open Access

https://doi.org/10.3390/nu12072032

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Abstract

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.

Highlights

Inflammatory bowel diseases (IBD) is an umbrella term that comprises the chronic inflammatory conditions of gastrointestinal tract, which are categorized as Crohn’s disease (CD) and ulcerative colitis (UC) [1,2].Though the exact mechanisms underlying the pathophysiology of UC are not clearly understood, it is a multifactorial disease where an interplay between environmental factors and genetic susceptibility, together with a dysregulated immune response, could be the major cause for the onset of this inflammatory condition [3,4]
We evaluated the effect of NED in colonic inflammation using both in vivo and in vitro models
MPO, IL-6, IL-1β, and tumor necrosis factor α (TNF-α) enzyme-linked immunosorbent assay (ELISA) kits were purchased from R&D systems (Minneapolis, MN, USA)

Summary

Introduction

Though the exact mechanisms underlying the pathophysiology of UC are not clearly understood, it is a multifactorial disease where an interplay between environmental factors and genetic susceptibility, together with a dysregulated immune response, could be the major cause for the onset of this inflammatory condition [3,4]. CD is categorized as inappropriate immune response of Th1 pathway and involvement of various mechanisms in different periods of disease progression [1]. UC is associated with impairment of gut barrier integrity [5], inflammatory and immune responses in the mucosa, and elevated oxidative stress [6,7,8,9,10]. The adverse effects associated with these prescription drugs over prolonged treatment periods, and the high relapse rates, limits their use [11,14]

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