Mechanistic Insights into Ameliorating Effect of Geraniol on d-Galactose Induced Memory Impairment in Rats

Abstract

Geraniol (GE), an important ingredient in several essential oils, displayed pleiotropic biological activities through targeting multiple signaling cascades. In the current study, we aimed to examine the protective effect of GE on d-galactose (d-gal) induced cognitive impairment and explore the underlying mechanisms. Forty male Wistar rats (8 weeks old) were randomly categorized into 4 groups; Group I (saline + vehicle [edible oil]), group II (saline + geraniol) (100 mg/kg/day orally), group III (d-galactose) (100 mg/kg/day subcutaneously injected), and group IV (d-galactose + geraniol). Behavioral impairments were evaluated. Brain levels of malondialdehyde (MDA) and reduced glutathione (GSH) as well as superoxide dismutase (SOD) and acetylcholinesterase (AchE) activities were estimated. The levels of inflammatory markers [tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, and nuclear factor kappa beta (NF-kβ)], endoplasmic reticulum stress sensors [inositol requiring protein 1(IRE1) and protein kinase RNA–like endoplasmic reticulum kinase (PERK)], brain-derived neurotrophic factor (BDNF), and mitogen-activated protein kinases (MAPK) pathway were measured by ELISA. Also, hippocampal histopathological assessment and immunohistochemical analysis of glial fibrillary acidic protein (GFAP) and caspase-3 were performed. Glucose regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) mRNA expression and protein levels were assessed. GE effectively ameliorated aging-related memory impairment through increasing GSH, BDNF, Ach levels, and SOD activity. Additionally, GE treatment caused a decrease in the levels of MDA, inflammatory mediators, and ER stress sensors as well as the AchE activity together with concomitant down-regulation of GRP78 and CHOP mRNA expression. Moreover, GE improved neuronal architecture and rat's spatial memory; this is evidenced by the shortened escape latency and increased platform crossing number. Therefore, GE offers a unique pharmacological approach for aging-associated neurodegenerative disorders. Graphical Abstract

Rutin attenuates d-galactose-induced oxidative stress in rats’ brain and liver: molecular docking and experimental approaches

“…45 recognized significant decreases in brain GPx and GST activities in d -gal-treated rats. Also, d -gal decreased the protein expression of SOD1 56 and SOD 57 activity in the brain of rats. Similarly, Motevalian et al 51 stated significant decreases in the expression of Sirt1, Bcl2, CAT, and GPx of d -gal-treated mice.…”

“…Similarly, IL-6 levels were increased in the rat brain. 57,59–61 Also, molecular docking study revealed high affinity of rutin to IL6RA and IL6RB indicating the ability of rutin to reduce aging-associated inflammatory process.…”

“…Binding free energy (kcal mol 57 reported an elevation in brain caspase-3 immunostaining expression in rat hippocampus. Also, in D-gal-treated rats, brain and heart levels of caspase-3, Bcl2, Bax, and CASP3.…”

Amelioration of Age-Related Multiple Neuronal Impairments and Inflammation in High-Fat Diet-Fed Rats: The Prospective Multitargets of Geraniol

“…Notably, the ameliorative effects of geraniol on cognitive performance are probably caused by modifications in lipid profiles. In addition, geraniol has been recently recommended as a viable therapeutic agent for enhancing cognitive function and neurotoxicity produced in rats [ 58 , 59 ].…”

“…Previously, geraniol was shown to have neuroprotective properties in an animal model of Parkinson's disease [ 58 ]. Recent studies demonstrated that geraniol treatment markedly boosted tyrosine hydroxylase, brain-derived neurotrophic factor (BDNF), and glial-derived neurotrophic factor (GDNF) and decreased apoptosis [ 26 , 58 , 59 ].…”