Sesamol defends neuronal damage following cerebral ischemia/reperfusion: a crosstalk of autophagy and Notch1/NLRP3 inflammasome signaling.

Autor: El-Sayyad SM; Faculty of Pharmacy, Pharmacology and Toxicology Department, October 6 University, Giza, 12585, Egypt., El-Ella DMA; Faculty of Pharmacy, Pharmacology and Toxicology Department, October 6 University, Giza, 12585, Egypt., Hafez MM; Faculty of Pharmacy, Biochemistry Department, Ahram Canadian University (ACU), Giza, Egypt., Al-Mokaddem AK; Faculty of Veterinary Medicine, Department of Pathology, Cairo University, Giza, 12211, Egypt., Ali BM; Faculty of Pharmacy, Department of Biochemistry, October 6 University, Giza, 12585, Egypt., Awny MM; Faculty of Pharmacy, Pharmacology and Toxicology Department, October 6 University, Giza, 12585, Egypt., El-Emam SZ; Faculty of Pharmacy, Pharmacology and Toxicology Department, October 6 University, Giza, 12585, Egypt. soadzakaria@o6u.edu.eg.
Jazyk: angličtina
Zdroj: Inflammopharmacology [Inflammopharmacology] 2024 Feb; Vol. 32 (1), pp. 629-642. Date of Electronic Publication: 2023 Oct 17.
DOI: 10.1007/s10787-023-01355-1
Abstrakt: Objective: Sesamol (SES) is a phenolic compound found in sesame seed oil. Several studies have revealed its anti-inflammatory and antioxidant properties. However, its complete underlying mechanistic perspective about cerebral ischemia/reperfusion (I/R) lesions has not yet been disclosed. Consequently, we aimed to scrutinize its neuroprotective mechanism against cerebral injury during a global cerebral I/R in a rat model, considering its impact on autophagy and Notch1/NLRP3 inflammasome signaling regulation.
Methods: To affirm our purpose, adult Wistar rats were allotted into five groups: sham and the other four groups in which transient global cerebral ischemia was induced by bilateral common ligation (2VO) for 1 h, then reperfusion for either 24 h or 5 days: I/R (1/24), I/R (1/5), SES + I/R (1/24), and SES + I/R (1/5). In treated groups, SES (100 mg/kg, p.o., for 21 days) was administered before cerebral I/R induction. The assessment of histopathological changes in brain tissues, immunohistochemistry, biochemical assays, ELISA, and qRT-PCR were utilized to investigate our hypothesis.
Results: Advantageously, SES halted the structural neuronal damage with lessened demyelination induced by cerebral I/R injury. Restoring oxidant/antioxidant balance was evident by boosting the total antioxidant capacity and waning lipid peroxidation. Furthermore, SES reduced inflammatory and apoptosis markers. Additionally, SES recovered GFAP, Cx43, and autophagy signaling, which in turn switched off the Notch-1/NLRP3 inflammasome trajectory.
Conclusions: Our results revealed the neuroprotective effect of SES against cerebral I/R injury through alleviating injurious events and boosting autophagy, consequently abolishing Notch1/NLRP3 inflammasome signaling.
(© 2023. The Author(s).)
Databáze: MEDLINE
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