The nicotinic derivatives, cotinine (COT), and 6-hydroxy-L-nicotine (6HLN), showed promising cognitive-improving effects without exhibiting the nicotine’s side-effects. Here, we investigated the impact of COT and 6HLN on memory impairment and the oxidative stress in the Aβ25-35-induced rat model of Alzheimer’s disease (AD). COT and 6HLN were chronically administered to Aβ25-35-treated rats, and their memory performances were assessed using in vivo tasks (Y-maze, novel object recognition, and radial arm maze). By using in silico tools, we attempted to associate the behavioral outcomes with the calculated binding potential of these nicotinic compounds in the allosteric sites of α7 and α4β2 subtypes of the nicotinic acetylcholine receptors (nAChRs). The oxidative status and acetylcholinesterase (AChE) activity were determined from the hippocampal tissues. RT-qPCR assessed bdnf, arc, and il-1β mRNA levels. Our data revealed that COT and 6HLN could bind to α7 and α4β2 nAChRs with similar or even higher affinity than nicotine. Consequently, the treatment exhibited a pro-cognitive, antioxidant, and anti-AChE profile in the Aβ25-35-induced rat model of AD. Finally, RT-qPCR analysis revealed that COT and 6HLN positively modulated the bdnf, arc, and il-1β genes expression. Therefore, these nicotinic derivatives that act on the cholinergic system might represent a promising choice to ameliorate AD conditions.

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Cotinine (COT) and 6-hydroxy-L-nicotine (6HLN) are two nicotinic derivatives that possess cognitive-improving abilities and antioxidant properties in different rodent models of Alzheimer’s disease (AD), eluding the side-effects of nicotine (NIC), the parent molecule. In the current study, we evaluated the impact of COT and 6HLN on memory deterioration, anxiety, and oxidative stress in the scopolamine (SCOP)-induced zebrafish model of AD. For this, COT and 6HLN were acutely administered by immersion to zebrafish that were treated with SCOP before testing. The memory performances were assessed in Y-maze and object discrimination (NOR) tasks, while the anxiety-like behavior was evaluated in the novel tank diving test (NTT). The acetylcholinesterase (AChE) activity and oxidative stress were measured from brain samples. The RT-qPCR analysis was used to evaluate the npy, egr1, bdnf, and nrf2a gene expression. Our data indicated that both COT and 6HLN attenuated the SCOP-induced anxiety-like behavior and memory impairment and reduced the oxidative stress and AChE activity in the brain of zebrafish. Finally, RT-qPCR analysis indicated that COT and 6HLN increased the npy, egr1, bdnf, and nrf2a gene expression. Therefore, COT and 6HLN could be used as tools for improving AD conditions.

We investigated the neuropharmacological effects of the methanolic extract from Lactuca capensis Thunb. leaves (100 and 200 mg/kg) for 21 days on memory impairment in an Alzheimer's disease (AD) rat model produced by direct intraventricular delivery of amyloid‐β1‐42 (Aβ1‐42). Behavioural assays such as Y‐maze and radial arm maze test were used for assessing memory performance. Aβ1‐42 decreased cognitive performance in the behavioural tests which were ameliorated by pre‐treatment with the methanolic extract. Acetylcholinesterase activity and oxidant–antioxidant balance in the rat hippocampus were abnormally altered by Aβ1‐42 treatment while these deficits were recovered by pre‐treatment with the methanolic extract. In addition, rats were given Aβ1‐42 exhibited in the hippocampus decreased brain‐derived neurotrophic factor (BDNF) mRNA copy number and increased IL‐1β mRNA copy number which was reversed by the methanolic extract administration. These findings suggest that the methanolic extract could be a potent neuropharmacological agent against dementia via modulating cholinergic activity, increasing of BDNF levels and promoting antioxidant action in the rat hippocampus.

Origanum L. (Lamiaceae) is an important genus of medicinal and aromatic plants used in traditional medicine since ancient times as culinary herbs and remedies. The aim of the present study was to evaluate the chemical composition, as well as the biochemical and cellular activities of freshly prepared Origanum majorana L. essential oil (OmEO) in an Alzheimer’s disease (AD) amyloid beta1-42 (Aβ1-42) rat model. OmEO (1% and 3%) was inhaled for 21 consecutive days, while Aβ1-42 was administered intracerebroventricularly to induce AD-like symptoms. Our data demonstrate that OmEO increased antioxidant activity and enhanced brain-derived neurotrophic factor (BDNF) expression, which in concert contributed to the improvement of cognitive function of animals. Moreover, OmEO presented beneficial effects on memory performance in Y-maze and radial arm-maze tests in the Aβ1-42 rat AD model.