Affiliations: [a] Gaziantep University, Medical Faculty, Physiology Department, Gaziantep University, Gaziantep, Turkey
| [b] Gaziantep University, Health Science Faculty, Nutrition and Dietetics Department, Gaziantep University, Gaziantep, Turkey
Correspondence:
[*]
Correspondence to: Ahmet Sarper Bozkurt, PhD, Department of Physiology, Gaziantep University, Medical Faculty, Gaziantep, Turkey. Tel.: +90 342 360 6060; Fax: +90 342 360 1617; E-mail: asbozkurt@gantep.edu.tr; ORCID: 0000-0002-7293-0974, and Şenay Görücü Yílmaz, PhD, Department of Nutrition and Dietetics, Gaziantep University, Health Science Faculty, Gaziantep, Turkey. Tel.: +90 342 360 1200; Fax: +90 342 360 8795; E-mail: gorucu@gantep.edu.tr;. ORCID: 0000-0003-0523-7819.
Abstract: Background:
Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by two main pathological mechanisms, mostly hyperphosphorylated tau and amyloid-β toxicity. Although many studies focus on these basic mechanisms, ferroptosis draws attention as an important pathway responsible for neurodegeneration in AD. There is no definitive treatment for AD but alternative phytochemicals to drugs come into prominence. Betulin is usually obtained from the birch tree. It is an abundant triterpene and has a high antioxidant capacity. Isthmin-1 (ISM1) is a secreted adipokine. Objective:
In this study, we investigated the potential treatment of AD in the ferroptosis-ISM1-betulin triangle. Methods:
For this, we created an AD model with okadaic acid (200 ng/kg)) in 36 Wistar albino male rats and treated with betulin (20 mg/kg/day, i.p). We evaluated ISM1 gene expression, iron accumulation, and total oxidative metabolism parameters (TAS, TOS, OSI) in hippocampal tissue. We analyzed cognitive recovery in AD with Morris Water Maze Test and general locomotor activity, explore, and anti-anxiolytic effect with Open Field Test. Results:
We compared the obtained data with metabolic and genetic results. In conclusion, betulin may have a role in neuronal ferroptotic mechanisms by reducing iron accumulation by ISM1 regulation. Conclusions:
Betulin may have a role in neuronal ferroptotic mechanisms by reducing iron accumulation by ISM1 regulation. Although this study suggests the corrective effect of betulin and ISM1 on cognitive gain and anxiety, it is the first study to show the total antioxidant capacity of betulin in AD.
