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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Safranal, a Natural Neuroprotective Compound, Modulates Plasma Iron Levels, Improves Behavioral Performance, and Demonstrates Dose-Specific Cytoprotection in Alzheimer’s Disease Models

  • Esra Tekin1
  • Meliha Koldemir Gündüz2
  • Zeynep Yığman3,4
  • Beyza Aydoğan Kara5,6
  • Ayşegül Küçük7
  • Mustafa Arslan6,8,9
9 affiliations
  1. 1Department of Physiology, Faculty of Medicine, Kırıkkale University, 71450 Kırıkkale, Türkiye
  2. 2Department of Engineering Basic Sciences, Faculty of Engineering and Natural Sciences, Kutahya Health Sciences University, 43100 Kutahya, Türkiye
  3. 3Department of Histology and Embryology, Faculty of Medicine, Gazi University, 06500 Ankara, Türkiye
  4. 4Neuroscience and Neurotechnology Center of Excellence (NÖROM), Gazi University, 06560 Ankara, Türkiye
  5. 5Department of Medical Services and Techniques, School of Health Services, Gazi University, 06830 Ankara, Türkiye
  6. 6Life Sciences Application and Research Center, Gazi University, 06830 Ankara, Türkiye
  7. 7Department of Physiology, Faculty of Medicine, Bandırma Onyedi Eylül University, 10200 Bandırma, Türkiye
  8. 8Department of Anesthesiology and Reanimation, Faculty of Medicine, Gazi University, 06500 Ankara, Türkiye
  9. 9Laboratory Animal Breeding and Experimental Research Center (GÜDAM), Gazi University, 06500 Ankara, Türkiye
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Abstract

Metal dyshomeostasis contributes to Alzheimer’s disease (AD) by influencing amyloid aggregation, oxidative imbalance, and impaired clearance mechanisms. Safranal, a bioactive constituent of Crocus sativus, exhibits antioxidant properties, but its metal-modulating actions remain insufficiently understood. This study investigated whether safranal modulates metal (Fe, Cu, Zn) levels in an AD rat model while evaluating its cytoprotective rescue capacity against Aβ1-42 induced neurotoxicity in differentiated SH-SY5Y cells. AD was induced in male rats via intracerebroventricular streptozotocin, followed by a four-week safranal administration (0.5 mg/kg/day, ip). Behavioral performance, plasma metal levels (ICP-MS), and cerebral total antioxidant capacity (FRAP) were evaluated alongside histological assessment. Post-treatment protocols were employed to evaluate the effects of safranal on cell viability and apoptosis in differentiated SH-SY5Y cells exposed to Aβ1-42. Longitudinal analyses revealed that safranal attenuated exploratory deficits and recognition memory impairments in AD rats. Decreased plasma iron levels in the AD group were restored by safranal, accompanied by a return of cerebral antioxidant capacity to normal. Although overt hippocampal histological alterations were absent in this early phase, post-treatment with safranal successfully offered a therapeutic rescue window, preserving cell viability and attenuating Aβ1-42-induced apoptotic features in vitro. Safranal demonstrates beneficial neuroprotective effects in AD models by improving behavioral outcomes, partially correcting plasma iron levels, and mediating cytoprotective rescue windows against Aβ1-42-induced cellular toxicity. These findings suggest that safranal represents a promising natural candidate for reducing behavioral deficits, supporting peripheral iron status, and offering functional cell survival in AD models.

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Cite

BibTeXRIS
BibTeX
@article{tekin2026safranal,
  title = {{Safranal, a Natural Neuroprotective Compound, Modulates Plasma Iron Levels, Improves Behavioral Performance, and Demonstrates Dose-Specific Cytoprotection in Alzheimer’s Disease Models}},
  author = {Esra Tekin and Meliha Koldemir Gündüz and Zeynep Yığman and Beyza Aydoğan Kara and Ayşegül Küçük and Mustafa Arslan},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27209392},
  url = {https://www.mdpi.com/1422-0067/27/20/9392},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Safranal, a Natural Neuroprotective Compound, Modulates Plasma Iron Levels, Improves Behavioral Performance, and Demonstrates Dose-Specific Cytoprotection in Alzheimer’s Disease Models
AU  - Esra Tekin
AU  - Meliha Koldemir Gündüz
AU  - Zeynep Yığman
AU  - Beyza Aydoğan Kara
AU  - Ayşegül Küçük
AU  - Mustafa Arslan
PY  - 2026
DA  - 2026/10/01
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27209392
UR  - https://www.mdpi.com/1422-0067/27/20/9392
AB  - Metal dyshomeostasis contributes to Alzheimer’s disease (AD) by influencing amyloid aggregation, oxidative imbalance, and impaired clearance mechanisms. Safranal, a bioactive constituent of Crocus sativus, exhibits antioxidant properties, but its metal-modulating actions remain insufficiently understood. This study investigated whether safranal modulates metal (Fe, Cu, Zn) levels in an AD rat model while evaluating its cytoprotective rescue capacity against Aβ1-42 induced neurotoxicity in differentiated SH-SY5Y cells. AD was induced in male rats via intracerebroventricular streptozotocin, followed by a four-week safranal administration (0.5 mg/kg/day, ip). Behavioral performance, plasma metal levels (ICP-MS), and cerebral total antioxidant capacity (FRAP) were evaluated alongside histological assessment. Post-treatment protocols were employed to evaluate the effects of safranal on cell viability and apoptosis in differentiated SH-SY5Y cells exposed to Aβ1-42. Longitudinal analyses revealed that safranal attenuated exploratory deficits and recognition memory impairments in AD rats. Decreased plasma iron levels in the AD group were restored by safranal, accompanied by a return of cerebral antioxidant capacity to normal. Although overt hippocampal histological alterations were absent in this early phase, post-treatment with safranal successfully offered a therapeutic rescue window, preserving cell viability and attenuating Aβ1-42-induced apoptotic features in vitro. Safranal demonstrates beneficial neuroprotective effects in AD models by improving behavioral outcomes, partially correcting plasma iron levels, and mediating cytoprotective rescue windows against Aβ1-42-induced cellular toxicity. These findings suggest that safranal represents a promising natural candidate for reducing behavioral deficits, supporting peripheral iron status, and offering functional cell survival in AD models.
SN  - 1422-0067
ER  -