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Peer-reviewedCC BY 4.0PLOS One

Early life stress caused glucose homeostasis impairment and anxiety-like behavior along with oxidative stress in adolescent male rat offspring: Protective effect of saffron extract

  • Siavash Shirzadeh Barough1
  • Behnam Saeidi2
  • Fateme Binayi3
  • Mina Salimi4
  • Fatemeh Siavoshi5
  • Roxana Karbaschi6
  • Mehdi Hedayati7
  • Homeira Zardooz8
8 affiliations
  1. 1Neurophysiology Research Center, Institute of Neuroscience and Cognition, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  2. 2Foot and Mouth Disease Reference Laboratory, Razi Vaccine and Serum Research Institute, Agricultural Research Education and Extension Organization (AREEO), Karaj, Iran
  3. 3Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  4. 4Traditional Medicine and Hydrotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
  5. 5Department of Physiology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
  6. 6Brain Mapping Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  7. 7Faculty of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  8. 8Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Abstract

Early life stress (ELS) significantly contributes to metabolic and psychological disorders by triggering oxidative stress and disrupting the hypothalamic–pituitary–adrenal (HPA) axis. This research examined ELS effects on redox status, along with anxiety-like behavior, in adolescent male Wistar rats, also assessing saffron (Crocus sativus L.) extract’s potential benefits. Rats were exposed to foot shock stress from postnatal days 15–19, with treatment groups receiving saline or saffron extract (10 mg/kg) via intraperitoneal injection. Control groups were maintained without stress exposure. Elevated Plus Maze (EPM) and Open Field Test (OFT) were used to evaluate anxiety-like behaviors. Corticosterone, glucose, and insulin levels, oxidative stress markers [malondialdehyde (MDA), glutathione (GSH), and catalase activity] in the plasma, pancreas, and amygdala were determined, and the HOMA-β index was estimated. Saffron extract markedly restored ELS effects by reducing fasting plasma glucose and corticosterone levels, while increasing insulin levels and the HOMA-β index in adolescent offspring. Additionally, saffron extract inhibited oxidative stress, evidenced by reduced MDA, normalized catalase activity, and augmented GSH levels in the plasma, pancreas, and amygdala. Behaviorally, saffron extract-treated rats exhibited diminished anxiety-like behaviors, characterized by increased time spent in the open arms of the EPM and the center zone in the OFT. This study suggests that ELS induces disturbances in glucose metabolism and anxiety-like behavior, accompanied by oxidative stress and increased HPA axis activity. The protective role of saffron extract underscores its capability to serve as a medicinal compound for preventing and treating stress-induced metabolic and anxiety disorders.

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Cite

BibTeXRIS
BibTeX
@article{barough2026early,
  title = {{Early life stress caused glucose homeostasis impairment and anxiety-like behavior along with oxidative stress in adolescent male rat offspring: Protective effect of saffron extract}},
  author = {Siavash Shirzadeh Barough and Behnam Saeidi and Fateme Binayi and Mina Salimi and Fatemeh Siavoshi and Roxana Karbaschi and Mehdi Hedayati and Homeira Zardooz},
  journal = {PLOS One},
  year = {2026},
  month = oct,
  doi = {10.1371/journal.pone.0359395},
  url = {https://doi.org/10.1371/journal.pone.0359395},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Early life stress caused glucose homeostasis impairment and anxiety-like behavior along with oxidative stress in adolescent male rat offspring: Protective effect of saffron extract
AU  - Siavash Shirzadeh Barough
AU  - Behnam Saeidi
AU  - Fateme Binayi
AU  - Mina Salimi
AU  - Fatemeh Siavoshi
AU  - Roxana Karbaschi
AU  - Mehdi Hedayati
AU  - Homeira Zardooz
PY  - 2026
DA  - 2026/10/07
JO  - PLOS One
DO  - 10.1371/journal.pone.0359395
UR  - https://doi.org/10.1371/journal.pone.0359395
AB  - Early life stress (ELS) significantly contributes to metabolic and psychological disorders by triggering oxidative stress and disrupting the hypothalamic–pituitary–adrenal (HPA) axis. This research examined ELS effects on redox status, along with anxiety-like behavior, in adolescent male Wistar rats, also assessing saffron (Crocus sativus L.) extract’s potential benefits. Rats were exposed to foot shock stress from postnatal days 15–19, with treatment groups receiving saline or saffron extract (10 mg/kg) via intraperitoneal injection. Control groups were maintained without stress exposure. Elevated Plus Maze (EPM) and Open Field Test (OFT) were used to evaluate anxiety-like behaviors. Corticosterone, glucose, and insulin levels, oxidative stress markers [malondialdehyde (MDA), glutathione (GSH), and catalase activity] in the plasma, pancreas, and amygdala were determined, and the HOMA-β index was estimated. Saffron extract markedly restored ELS effects by reducing fasting plasma glucose and corticosterone levels, while increasing insulin levels and the HOMA-β index in adolescent offspring. Additionally, saffron extract inhibited oxidative stress, evidenced by reduced MDA, normalized catalase activity, and augmented GSH levels in the plasma, pancreas, and amygdala. Behaviorally, saffron extract-treated rats exhibited diminished anxiety-like behaviors, characterized by increased time spent in the open arms of the EPM and the center zone in the OFT. This study suggests that ELS induces disturbances in glucose metabolism and anxiety-like behavior, accompanied by oxidative stress and increased HPA axis activity. The protective role of saffron extract underscores its capability to serve as a medicinal compound for preventing and treating stress-induced metabolic and anxiety disorders.
SN  - 1932-6203
ER  -