Dissecting the antidepressant efect of troxerutin: modulation of neuroinfammatory and oxidative stress biomarkers in lipopolysaccharide‐treated mice

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Date

2024-06-29

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Naunyn-Schmiedeberg's Archives of Pharmacology

Abstract

The role of neuroinfammation in the pathogenesis of depression has prompted the search for new antidepressants. Troxerutin, a biofavonoid with anti-infammatory and antioxidant properties, has shown promise, but its impact on neurobehavioral functions remains poorly understood. This study aimed to investigate the antidepressant potential of troxerutin and its efect on the neuroinfammatory response. Here, we exposed male Swiss mice (n=5/group) to various treatments, including naive and negative controls receiving distilled water, troxerutin-treated groups administered at diferent doses (10, 20, 40 mg/kg, i.p.), and an imipramine-treated group (25 mg/kg, i.p.). After seven days of treatment, with the exception of the naive group, mice were administered a single dose of lipopolysaccharide (LPS, 0.83 mg/kg). Behavioral evaluations, consisting of the novelty-suppressed feeding (NSF) test, forced swim test (FST), and open feld test (OFT), were conducted. Additionally, brain samples were collected for biochemical and immunohistochemical analyses. Troxerutin signifcantly reduced immobility time in the FST and mitigated behavioral defcits in the NSF test. Additionally, troxerutin increased glutathione (GSH) and superoxide dismutase (SOD) levels while reducing nitrite, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interferon-gamma (IFN-γ) levels compared to the negative control. Immunohistochemistry analysis revealed decreased expression of inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB) in troxerutin- treated mice. Overall, these fndings suggest that troxerutin exerts signifcant antidepressive-like efects, likely mediated by its anti-infammatory and antioxidant mechanisms. The reduction in neuroinfammatory and oxidative stress biomarkers, along with the improvement in behavioral outcomes, underscores troxerutin's potential as a therapeutic agent for depression.

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Depression · Oxidative stress · Neuroinfammation · Neurobehavior · Troxerutin

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