The methanolic extract of Cinnamomum zeylanicum bark improves formaldehyde-induced neurotoxicity through reduction of phospho-tau (Thr231), inflammation, and apoptosis

Sara Sayad-Fathi; Arash Zaminy; Parvin Babaei; Fatemeh Yousefbeyk; Nasibeh Azizi; Ebrahim Nasiri

The methanolic extract of Cinnamomum zeylanicum bark improves formaldehyde-induced neurotoxicity through reduction of phospho-tau (Thr231), inflammation, and apoptosis

EXCLI J. 2020 May 25:19:671-686. eCollection 2020.

Authors

Sara Sayad-Fathi^{1

2}, Arash Zaminy², Parvin Babaei³, Fatemeh Yousefbeyk⁴, Nasibeh Azizi⁵, Ebrahim Nasiri^{1

2}

Affiliations

¹ Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
² Neuroscience Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
³ Department of Physiology, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
⁴ Department of Pharmacognosy, School of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran.
⁵ Department of Medicinal Chemistry, School of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran.

PMID: 32536837
PMCID: PMC7290100

Abstract

Accumulation of formaldehyde (FA) in the brain is linked to age-related neurodegenerative disorders, as it accelerates memory impairment through tau protein aggregation, inflammation, and nuclear damage. This study aimed to assess the possible effects of methanolic cinnamon extract (CE) on FA-induced neurotoxicity in rats. The animals were treated with CE (100, 200, and 400 mg/kg, P.O.) for 30 days following FA administration (60 mg/kg, I.P.) for 30 days. Briefly, spatial and inhibitory memory were examined by Morris water maze (MWM) and passive avoidance (PA) tasks, respectively. The Nissl, Hoechst, and Bielschowsky silver staining methods were also used to assess apoptosis and neurofibrillary tangles (NFTs) in the hippocampal CA1 region, respectively. Brain tissues were probed with an anti-phospho-tau (Thr²³¹) monoclonal antibody to assess tau hyperphosphorylation. Inflammatory cytokines (IL-1β, IL-6, and TNF-α) were also measured by ELISA assay. Western blotting was performed to quantify the amount of phospho-tau (Thr²³¹), caspase-8, and caspase-9. The results showed that FA injection significantly caused tau hyperphosphorylation at Thr²³¹ residue, which in turn disturbed the MWM performance. The ratio of apoptotic to intact neurons increased following FA treatment. The results of Western blotting indicated that the hippocampal levels of phospho-tau (Thr²³¹) and caspase-8 were significantly higher in the FA group compared to the control group. The hippocampal levels of IL-1β, IL-6, and TNF-α in the FA group were also higher than the control group. Administration of 200 mg/kg of CE significantly improved the rats' MWM performance, decreased the levels of phospho-tau (Thr²³¹), caspase-8, IL-6, and TNF-α, and reduced the ratio of apoptotic to intact neurons. Overall, cinnamon improved cognitive performance in FA-treated rats by eliminating tau hyperphosphorylation, inflammatory cytokines, and nuclear damage.

Keywords: Cinnamomum zeylanicum; formaldehyde; neurotoxicity; spatial memory; tauopathy.