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Honey protects against chronic unpredictable mild stress induced- intestinal barrier disintegration and hepatic inflammation

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A Correction to this article was published on 24 March 2021

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Abstract

Chronic stress is linked to liver injury by increasing intestinal permeability to lipopolysaccharide (LPS), which in turn can result in systemic and liver inflammation and damage. Beneficial effect of honey in the prevention of liver injury has been shown in previous studies, but mechanisms underlying are still less known. Here, we examined the therapeutic impacts of honey on intestinal nuclear factor-κB (NF-κB; an important regulator of stress-induced immune and inflammatory responses) and ileal tight junction (TJ) proteins of claudin-1 and ZO-1, serum LPS, liver inflammation and oxidative markers of malondialdehyde (MDA), nitric oxide (NO), (erythroid-derived 2)-like 2 (Nrf2), tumor necrosis factor (TNF)-α and total antioxidant capacity (TAC) following chronic unpredictable mild stress (CUMS) using Western blotting, ELISA kit and spectrophotometry. Male rats were subjected to CUMS for 28 consecutive days. Honey (0.2 and 2 g/kg/day, by gavage) was administered pretreatment (10 days) and during stress. Honey reduced stress-induced LPS elevation by preventing reduction in the intestinal TJ proteins of claudin-1 and ZO-1, while did not affect NF-kB levels. In liver, honey significantly suppressed stress-induced increase in MDA, NO, TNF-α and Nrf2 expression and normalized TAC. Noteworthy, honey high-dose provoked a greater decrease in TNF-α, Nrf2 and LPS levels than honey low-dose. Together, our study indicated that honey protects against stress-induced liver damage by modulating at least two pathways; intestinal barrier protection via increased TJ protein complex expression, and hepatic TAC protection that may be involved in the inhibition of MDA, NO, TNF-α and Nrf2 expression.

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Acknowledgements

This work was supported by the Isfahan University of Medical Sciences (Grant number 198158 to M.G.). This work did involve animals (rats). The experimental procedures were approved by the Ethics Committee of the Isfahan University of Medical Sciences in accordance with ethical guidelines for the Care and Use of Laboratory Animals (IR.MUI.RESEARCH.REC.1398.533).

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Authors and Affiliations

  1. Neurophysiology Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran

    Nasrin Mehranfard

  2. Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    Azadeh Yazdi, Asiye Rafiee Sardooi & Maedeh Ghasemi

  3. PhD of Anatomical Science, Department of Anatomy, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    Zeinab Shakerin

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  1. Nasrin Mehranfard
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Correspondence to Maedeh Ghasemi.

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The original online version of this article was revised: The correct spelling of the 3rd author’s name is Asiye Rafiee Sardooi.

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Mehranfard, N., Yazdi, A., Sardooi, A.R. et al. Honey protects against chronic unpredictable mild stress induced- intestinal barrier disintegration and hepatic inflammation. Mol Biol Rep 47, 8475–8484 (2020). https://doi.org/10.1007/s11033-020-05888-4

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