The effect of 3’,4’-dihydroxyflavonol (DiOHF) on endoplasmic reticulum stress in the cerebellum during brain ischemia-reperfusion


Akkaya G., Acar G., Aladag T., BALTACI S. B., Mogulkoc R., Baltaci A. K.

Nutritional Neuroscience, cilt.29, sa.2, ss.126-138, 2026 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 29 Sayı: 2
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1080/1028415x.2025.2545513
  • Dergi Adı: Nutritional Neuroscience
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, CINAHL, EMBASE, MEDLINE
  • Sayfa Sayıları: ss.126-138
  • Anahtar Kelimeler: 3',4'-dihydroxyflavonol, Bax, Bcl-2, CHOP, GRP78, HSP70, Ischemia/reperfusion, rat
  • İstanbul Medipol Üniversitesi Adresli: Evet

Özet

Ischemia is a condition occured when there is insufficient blood flow to the tissues, negatively affecting cellular energy production. Brain ischemia is a critical pathological process caused neuronal function to deteriorate and cell death due to the temporary or permanent interruption of cerebral blood circulation. During this process, triggering endoplasmic reticulum (ER) stress disrupts intracellular protein folding mechanisms, leading to increased neuronal damage. This study investigated the effect of a 1-week supplementation with 3’,4’-Dihydroxyflavonol (DiOHF) on endoplasmic reticulum stress in cerebellum tissue after cerebral ischemia-reperfusion. The study was conducted on 28 male Wistar-albino rats. Control: No anesthesia or surgical procedure was applied. Sham: The carotid artery regions were opened and closed under general anesthesia. After the application, solvent application was performed for 1 week (1 ml DiOHF vehicle). Ischemia-Reperfusion: After isolating the carotid arteries, ischemia was performed by ligating them for 30 minutes, followed by reperfusion. Ischemia-Reperfusion + DiOHF: After ischemia was performed for 30 minutes, reperfusion was allowed. DiOHF supplementation was performed for 1 week. After one week of treatment, animals were killed and cerebellum tissues were taken to evaluate GRP78, HSP70, CHOP, Bcl-2 and Bax levels. While I/R increased GRP78 (p < 0,05), HSP70 (p < 0,05), CHOP (p < 0,05) and Bax (p < 0,05) values in the cerebellum, it resulted in significant downregulation of BCl-2 levels (p < 0,05). However, 3',4'-Dihydroxyflavonol application for 1 week corrected the deteriorations caused by I/R. The study results show that 1 week of 3',4'-Dihydroxyflavonol treatment after I/R provides significant correction in endoplasmic reticulum stress related parameters caused by focal brain I/R in the cerebellum, suggesting that DiOHF may serve as a promising therapeutic candidate for defending cerebellar tissue from ER stress-related post-ischemic damage.