Ferulic Acid Reverses the Cognitive Dysfunction Caused by Amyloid β Peptide 1-40 Through Anti-Oxidant Activity and Cholinergic Activation in Rats

Abstract

Cholinergic dysfunction and oxidation stress are the dominant mechanisms of memory deficit in Alzheimer's disease (AD). This study describes how ferulic acid (FA) ameliorates cognitive deficits induced by mecamylamine (MECA), scopolamine (SCOP), central acetylcholinergic neurotoxin ethylcholine mustard aziridinium ion (AF64A) and amyloid β peptide (Aβ1-40). This study also elucidates the role of anti-oxidant enzymes and cholinergic marker acetylcholinesterase (AChE) in the reversal of FA from Aβ1-40-induced cognitive deficits in rats. At 100 mg/kg, FA attenuated impairment induced by MECA and SCOP plus MECA; however, this improvement was not blocked by the peripheral muscarinic receptor antagonist scopolamine methylbromide (M-SCOP). At 100 and 300 mg/kg, FA also attenuated the impairment of inhibitory passive avoidance induced by AF64A. Further, FA attenuated the performance impairment and memory deficit induced by Aβ1-40 in rats, as did vitamin E/C. FA reversed the deterioration of superoxide dismutase (SOD) and AChE activities, and the glutathione disulfide (GSSG) and glutathione (GSH) levels in the cortex and hippocampus. Vitamin E/C only selectively reversed deterioration in the hippocampus. We suggest that FA reduced the progression of cognitive deficits by activating central muscarinic and nicotinic receptors and anti-oxidant enzymes.

Mori Fructus improves cognitive and neuronal dysfunction induced by beta-amyloid toxicity through the GSK-3β pathway in vitro and in vivo

“…Caffeic acid attenuated tau phosphorylation by the reduction of GSK-3β activation against Aβ-induced neurotoxicity (Sul et al, 2009). Quercetin, chlorogenic acid, and ferulic acid have been shown to protect cognitive dysfunction and neuronal damage in several experimental models by inhibiting apoptosis, oxidative stress, autophagy, and inflammation, underlying pathways of AD-like pathological condition (Joseph et al, 2010;Sabogal-Guáqueta et al, 2015;Tsai et al, 2015). We hypothesize that the multiple bioactive effects of ME on neuroassociated models and its various phytochemicals contributed to the neuroprotective effect observed in the present study.…”

Ferulic acid ameliorates memory impairment in d-galactose-induced aging mouse model

“…Inhibition of AChE has been used as a therapeutic strategy for Alzheimer's disease and other types of dementia (Lle o et al 2006). The previous study demonstrated that FA could reverse the cognitive deficits caused by Ab 1-40 though suppress AChE activity in rats with a dose-dependent manner (Tsai et al 2015). We also found that the high activity of AChE in D-gal-treated mice brain could be notably inhibited by chronic administration of FA (100 mg/kg), but it could not be significantly inhibited by lower dose of FA (50 mg/kg), which maybe one of the reasons that the study results of Yan et al (2001) showed no significant difference.…”

“…Our study confirmed using Pearson's correlation analysis that oxidative damage in the brain contributes to the spatial memory deficit in D-gal-treated mice. FA, a small molecule phenolic acid, can transport across the blood-brain barrier and ameliorated oxidative stress induced by Ab 1-40 which might be attributed to the hydroxyl group on the benzene ring (Barone et al, 2009;Wu et al 2014;Tsai et al 2015). It indicates that FA possesses protective effect against oxidative stress in the brain.…”

The Gut Microflora and its Metabolites Regulate the Molecular Crosstalk between Diabetes and Neurodegeneration

“…FA was shown to directly inhibit the memory impairment of Aβ1-40 induced AD in rats while reversing the deterioration of anti-oxidative factors. FA also rescued the compromised acetylcholine esterase activity characteristic of the AD phenotype [98]. These effects are likely administered by the combined anti-inflammatory, anti-oxidative and enhanced choline acetyltransferase activity of FA [99].…”