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Idebenone Protects against Spontaneous Chronic Murine Colitis by Alleviating Endoplasmic Reticulum Stress and Inflammatory Response. | LitMetric

Idebenone Protects against Spontaneous Chronic Murine Colitis by Alleviating Endoplasmic Reticulum Stress and Inflammatory Response.

Biomedicines

Gut Health Laboratory, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston 7250, Tasmania, Australia.

Published: September 2020

Endoplasmic reticulum (ER) stress in intestinal secretory goblet cells has been linked to the development of ulcerative colitis (UC). Emerging evidence suggests that the short chain quinone drug idebenone displays anti-inflammatory activity in addition to its potent antioxidant and mitochondrial electron donor properties. This study evaluated the impact of idebenone in mice, that are characterized by spontaneous chronic intestinal inflammation and ER stress caused by a missense mutation in the mucin gene. Idebenone (200 mg/kg) was orally administered daily to 5-6 weeks old mice over a period of 21 days. Idebenone treatment substantially improved body weight gain, disease activity index (DAI), colon length and histopathology score. Immunohistochemistry revealed increased expression of MUC2 protein in goblet cells, consistent with increased mRNA levels. Furthermore, idebenone significantly reduced the expression of the ER stress markers C/EBP homologous protein (), activating transcription factor 6 () and X-box binding protein-1 () at both mRNA and protein levels. Idebenone also effectively reduced pro-inflammatory cytokine levels in colonic explants. Taken together, these results indicate that idebenone could represent a potential therapeutic approach against human UC by its strong anti-inflammatory activity and its ability to reduce markers of ER stress.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601570PMC
http://dx.doi.org/10.3390/biomedicines8100384DOI Listing

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