Involvement of indoleamine 2, 3-dioxygenase (IDO) and brain-derived neurotrophic factor (BDNF) in the neuroprotective mechanisms of ferulic acid against depressive-like behaviour

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Mallik, Sanchari Basu
Mudgal, Jayesh
Kinra, Manas
Hall, Susan
Grant, Gary D
Anoopkumar-Dukie, Shailendra
Nampoothiri, Madhavan
Zhang, Yuqing
Arora, Devinder
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2023
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Abstract

Objective: Ferulic acid (FA) is a common food ingredient that is abundantly present in various routinely consumed food and beverages. Like many cinnamic acid derivatives, FA produces wide-ranging effects in a dose-dependent manner and various studies link FA consumption with reduced risk of depressive disorders. The aim of this study was to exploit the neuroprotective mechanisms of FA including indoleamine 2,3-dioxygenase (IDO), brain-derived neurotrophic factor (BDNF), and other pro-inflammatory cytokines by employing lipopolysaccharide (LPS)-induced depressive-like behaviour model. Methods: C57BL/6J male mice were divided into 4 groups consisting of saline (SAL), LPS, FA and Imipramine (IMI). Animals were pretreated orally with FA (10 mg/kg) and IMI (10 mg/kg) for 21 days once daily and all groups except SAL were challenged with LPS (0.83 mg/kg) intraperitoneally on day 21. Results: LPS administration produced a biphasic change in the behaviour of the animals where the animals lost a significant weight and express high immobility time at 24 h. Proinflammatory cytokines including, TNF-α, IL-6, IL-1β, and IFN-γ were significantly increased along with increased lipid peroxidation and reduced BDNF. Furthermore, the increased kynurenine to tryptophan ratio was indicative of elevated IDO activity. Conclusion: The results of this study emphasise that low dose of FA is effective in attenuating depressive-like behaviour by modulating IDO, BDNF and reducing neuroinflammation.

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Metabolic Brain Disease

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© The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Biochemistry and cell biology

Clinical sciences

Neurosciences

Biological psychology

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Life Sciences & Biomedicine

Endocrinology & Metabolism

Neurosciences & Neurology

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Mallik, SB; Mudgal, J; Kinra, M; Hall, S; Grant, GD; Anoopkumar-Dukie, S; Nampoothiri, M; Zhang, Y; Arora, D, Involvement of indoleamine 2, 3-dioxygenase (IDO) and brain-derived neurotrophic factor (BDNF) in the neuroprotective mechanisms of ferulic acid against depressive-like behaviour, Metabolic Brain Disease, 2023

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