{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Physiology, Faculty of Medicine, Kırıkkale University, 71450 Kırıkkale, Türkiye",
    "Department of Engineering Basic Sciences, Faculty of Engineering and Natural Sciences, Kutahya Health Sciences University, 43100 Kutahya, Türkiye",
    "Department of Histology and Embryology, Faculty of Medicine, Gazi University, 06500 Ankara, Türkiye",
    "Neuroscience and Neurotechnology Center of Excellence (NÖROM), Gazi University, 06560 Ankara, Türkiye",
    "Department of Medical Services and Techniques, School of Health Services, Gazi University, 06830 Ankara, Türkiye",
    "Life Sciences Application and Research Center, Gazi University, 06830 Ankara, Türkiye",
    "Department of Physiology, Faculty of Medicine, Bandırma Onyedi Eylül University, 10200 Bandırma, Türkiye",
    "Department of Anesthesiology and Reanimation, Faculty of Medicine, Gazi University, 06500 Ankara, Türkiye",
    "Laboratory Animal Breeding and Experimental Research Center (GÜDAM), Gazi University, 06500 Ankara, Türkiye"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Esra Tekin"
    },
    {
      "affs": [
        1
      ],
      "name": "Meliha Koldemir Gündüz",
      "orcid": "0000-0003-0969-6377"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Zeynep Yığman"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Beyza Aydoğan Kara"
    },
    {
      "affs": [
        6
      ],
      "name": "Ayşegül Küçük"
    },
    {
      "affs": [
        5,
        7,
        8
      ],
      "name": "Mustafa Arslan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7b8fa6xbqz65e.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27209392",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705250/?tool=EBI",
  "id": "7b8fa6xbqz65e",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/20/9392",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2730|Saffron Plant Research Studies"
    ]
  ],
  "openalex": "W7223398962",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705250/pdf/?tool=EBI",
  "pmcid": "PMC13705250",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/7b8fa6xbqz65e.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:57Z",
      "native_id": "10.3390/ijms27209392",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/20/9392"
    },
    {
      "first_seen": "2026-10-30T12:21:45Z",
      "native_id": "PMC:PMC13705250",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13705250"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Saffron Plant Research Studies",
      "subfield": "oncology"
    }
  ],
  "title": "Safranal, a Natural Neuroprotective Compound, Modulates Plasma Iron Levels, Improves Behavioral Performance, and Demonstrates Dose-Specific Cytoprotection in Alzheimer’s Disease Models",
  "title_text": "Safranal, a Natural Neuroprotective Compound, Modulates Plasma Iron Levels, Improves Behavioral Performance, and Demonstrates Dose-Specific Cytoprotection in Alzheimer’s Disease Models",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:45Z",
  "url": "https://research.draconitic.com/paper/7b8fa6xbqz65e",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}