Evidence map›Paper›PMID 42557968›Full record

ArticleAnimal models and experimental medicine2026

Multipathway modulation of neuroinflammation and oxidative stress by hesperidin in a rat single prolonged stress model of post-traumatic stress disorder.

Godson Emeka Anyanwu, Ogan Christopher Akanaku, Augustine Oviosun, Precious E Ekwueme, Paul Anyiom Odey, Chima Paul Okechukwu Ugwu, Chinyere Nkemjika Anyanwu

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Article in Animal models and experimental medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

7 authors.

Godson Emeka AnyanwuDepartment of Anatomy, Faculty of Biomedical Sciences, Kampala International University, Kampala, Uganda.ORCID https://orcid.org/0000-0002-7367-807X
Ogan Christopher AkanakuDepartment of Anatomy, Faculty of Basic Medical Sciences, University of Cross River State, Calabar, Nigeria.
Augustine OviosunDepartment of Anatomy, Faculty of Biomedical Sciences, Kampala International University, Kampala, Uganda.
Precious E EkwuemeDepartment of Anatomy, Faculty of Basic Medical Sciences, College of Medicine, University of Nigeria, Enugu Campus, Enugu, Nigeria.
Paul Anyiom OdeyDepartment of Anatomy, Faculty of Basic Medical Sciences, University of Calabar, Calabar, Cross River State, Nigeria.
Chima Paul Okechukwu UgwuDepartment of Anatomy, Faculty of Basic Medical Sciences, University of Calabar, Calabar, Cross River State, Nigeria.
Chinyere Nkemjika AnyanwuDepartment of Microbiology and Immunology, Faculty of Biomedical Sciences, Kampala International University, Kampala, Uganda.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPost-traumatic stress disorder (PTSD) is a complicated neuropsychiatric disorder that is marked by long-term neuroinflammation, oxidative stress, and poor neuroplasticity in stress-sensitive brain areas. Hesperidin is a citrus-derived flavanone glycoside that has been reported to have multitarget neuroprotective effects with antioxidant, anti-inflammatory, and neurotrophic regulatory activities. However, its integrated effects across convergent pathological pathways in validated PTSD models remain insufficiently defined.

methodsMale Wistar rats were subjected to the single prolonged stress (SPS) paradigm and treated with hesperidin (50, 100, and 200 mg/kg), fluoxetine (20 mg/kg), or vehicle for 14 days. Biochemical assessments (malondialdehyde [MDA], catalase [CAT], superoxide dismutase [SOD]) and immunohistochemical measurements of neuronal and glial integrity (NeuN, glial fibrillary acidic protein [GFAP], brain-derived neurotrophic factor [BDNF]) in the hippocampus, amygdala, and prefrontal cortex were performed.

resultsSPS exposure induced marked oxidative imbalance, evidenced by increased MDA levels and reduced CAT activity, alongside significant upregulation of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and IL-1β, increased astrocytic reactivity (GFAP), and reduced BDNF expression. Hesperidin treatment significantly attenuated lipid peroxidation, partially restored CAT activity, and suppressed pro-inflammatory cytokines, with the most pronounced effect observed for IL-1β. Notably, hesperidin reduced astrocytic activation and preserved neuronal morphology, while enhancing BDNF expression in a dose-dependent manner, with optimal effects at 50-100 mg/kg. Conversely, there was little group variation in the activity of SOD, implying pathway-selective redox regulation.

conclusionHesperidin has multipathway, coordinated, modulatory effects on oxidative stress, neuroinflammation, glial activation, and neurotrophic signaling in the SPS model of PTSD. These findings support its utility as a mechanistic probe for interrogating convergent stress-related neuropathological pathways.

Indexed as

amygdalahesperidinhippocampusneuroinflammationoxidative stresspost‐traumatic stress disorderprefrontal cortexsingle prolonged stress

Identifiers

PMID42557968
PMCPMC13444398

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.