Caspian Journal of Veterinary Sciences

Caspian Journal of Veterinary Sciences

Neuroprotective effects of nanophytosome-encapsulated citral on subcortical NGF gene expression and cortisol regulation in a mouse model of chronic unpredictable mild stress

Articles in Press

Document Type : Original Article

Authors
Mohammad Amin Sharajpour 1
Sedigheh Khanjani Jelodar 1
Akbar Hajizadeh Moghaddam 1
Hakimeh Gavzan 2
Mohammad Amin Mashayekhpour 1
1 Department of Animal Sciences, Faculty of Science, University of Mazandaran, Babolsar, Iran.
2 Department of Basic Sciences, Faculty of Veterinary Medicine, Amol University of Special Modern Technologies, Amol, Iran.
10.22034/cjvs.2026.581077.1065
Abstract
Chronic unpredictable mild stress (CUMS) induces profound neuroendocrine and neurotrophic disturbances that contribute to depressive‑like phenotypes, particularly through impaired subcortical plasticity and dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis. This study evaluated the neuroprotective effects of nanophytosome‑encapsulated citral on subcortical nerve growth factor (NGF) gene expression and cortisol regulation in a CUMS mouse model. Twenty eight adult male mice were assigned to four experimental groups, including control, a CUMS (subjected to a six-week CUMS protocol), and two CUMS groups treated with citral-loaded nanophytosomes at doses of 20 and 50 mg/kg. All treatments were administered three times weekly during weeks 4–6. Behavioral assessments were complemented by molecular and biochemical analyses to quantify NGF mRNA levels assessed by Quantitative real-time PCR (qRT-PCR) in subcortical regions and circulating cortisol concentrations. CUMS exposure was associated with a significant downregulation of NGF expression, assessed by qRT-PCR, along with elevated cortisol levels measured by enzyme-linked immunosorbent assay (ELISA), indicating impaired neurotrophic support and HPA axis hyperactivation. Treatment with citral nanophytosomes produced robust antidepressant‑like effects, characterized by partial restoration of NGF transcriptional activity and normalization of cortisol levels toward physiological ranges. These findings suggest that nanophytosome‑based delivery substantially enhances the neuroprotective efficacy of citral, enabling simultaneous modulation of neurotrophic and endocrine pathways implicated in depression. By targeting both NGF‑mediated neuronal resilience and stress‑induced glucocorticoid imbalance, citral nanophytosomes represent a mechanistically integrated and translationally relevant strategy for developing next‑generation antidepressant interventions.
Keywords
Citral nanophytosome
Cortisol
Depression
Mice
Stress
Subjects
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Caspian Journal of Veterinary Sciences

Articles in Press, Accepted Manuscript
Available Online from 08 November 2026

  • Receive Date 11 May 2026
  • Revise Date 23 August 2026
  • Accept Date 23 August 2026