The Protective Effects of Trans-Cinnamaldehyde against D-Galactose and Aluminum Chloride-Induced Cognitive Dysfunction in Mice

Abstract

The increased prevalence of cognitive impairment, specifically among the aging population, has attracted attention in recent years. Trans-cinnamaldehyde (TCA), which is isolated from cinnamon, has recently drawn attention because of its potent anti-inflammatory and antioxidant properties. This study aimed to investigate the effects of TCA on learning and memory using a mouse model of cognitive impairment induced by a combination of D-galactose (D-gal) and aluminum chloride (AlCl3). TCA (10 and 30 mg/kg/day) was administered orally for 30 days after the induction of cognitive impairment. The Morris water maze (MWM) task was performed to directly evaluate the neuroprotective effects of TCA on memory and spatial learning abilities. We found that TCA treatment attenuated cognitive impairment and reduced brain damage in the D‑gal- and AlCl3-treated mice. To further investigate the mechanisms involved in the effects of TCA, we analyzed the nuclear factor erythroid 2-related factor (Nrf2) and related signaling pathways. We found that TCA upregulated AMP-activated protein kinase (AMPK), Nrf2, heme oxygenase 1 (HO-1) and NAD(P)H dehydrogenase [quinone] 1 (NQO-1); this suggests that TCA may attenuate cognitive dysfunction by reducing oxidative stress. We concluded that TCA reduced D-gal and AlCl3-induced cognitive dysfunction through activation of the AMPK-mediated Nrf2/HO-1 signaling pathway in the brain. These results suggest that TCA may be a candidate for treating age-associated cognitive impairment.