Investigation of neuroprotective and antiapoptotic effects of rosmarinic acid in an in vitro Alzheimer’s disease model

Objective(s): Rosmarinic acid (RA) exhibits anti-oxidant, anti-aging, and anti-inflammatory properties. This study aimed to investigate the effects of RA on amyloid beta (Aβ), phosphorylated tau (p-tau), α-synuclein (α-syn), Abelson tyrosine kinase (Abl), and apoptotic markers in an in vitro Alzheimer’s disease (AD) model.Materials and Methods: SH-SY۵Y cells were differentiated into cholinergic neurons by all-trans retinoic acid (ATRA). CCK-۸ assay was performed to determine the concentrations of Aβ, RA, and Aβ+RA on differentiated cells (D-cholinergic neurons). Then, control (D), D+Aβ, pretreatment (D+Aβ+RA), and D+RA groups were formed. Gene expression levels of apoptotic biomarkers were evaluated using qRT-PCR. Aβ, α-syn, Abl, p-tau, caspase-۷ (CASP۷), BAX, and cytochrome c (CYCS) protein levels were determined by ELISA. Results: CCK-۸ assay showed that RA (۰.۵–۵ µM) was non-toxic to differentiated cells, and the IC₄₀ of Aβ₁₋₄₂ was ۲۰ µM. Pretreatment with ۱.۵ µM RA protected cells from Aβ-induced toxicity. Gene expression analysis revealed that apoptotic markers (BAX, BLC۲, CYCS, CASP۳, CASP۷, FAS, FADD) were significantly increased in the D+Aβ group compared to the control, whereas their levels were markedly reduced in the D+Aβ+RA group relative to the D+Aβ group. ELISA results corroborated qRT-PCR findings for CASP۷, BAX, and CYCS. Additionally, RA decreased Aβ, α-syn, and p-tau protein levels, while Abl levels increased only in the D+RA group.Conclusion: RA exhibits neuroprotective and antiapoptotic effects by modulating apoptotic markers and reducing pathological proteins in an in vitro AD model.

کلیدواژه ها:

Alzheimer&rsquo ، s Disease ، Apoptosis ، Neuroprotective agents ، Rosmarinic acid ، Cell line