Central nervous system agents in medicinal chemistry最新文献

Background: Antidepressant properties of melatonin and atorvastatin have been reported by clinical and experimental studies. Since both melatonin and atorvastatin possess antioxidant properties and considering the involvement of oxidative stress factors in depression, the aim of the present investigation was to study the possible role of oxidative stress factors in the antidepressant- like effect of melatonin and atorvastatin combination in mice forced swimming test.

Methods: Following the induction of restraint stress, mice were randomly divided into eight groups including the non-stressed and stressed vehicle-treated groups, melatonin- and atorvastatintreated groups, a combination of melatonin and atorvastatin-treated group, and fluoxetineadministrated group. The open field test (OFT) and forced swimming test (FST) were carried out, and the hippocampus and prefrontal cortex were removed for the measurement of oxidative stress factors.

Results: Induction of restraint stress increased the immobility time in FST, and melatonin (10 mg/kg) significantly reduced it. Atorvastatin at both doses of 1 and 10 mg/kg could not alter the immobility time, significantly. Co-administration of melatonin and atorvastatin (10 mg/kg) exerted a significant antidepressant-like response and decreased the immobility time compared with melatonin or atorvastatin (10 mg/kg), alone. Induction of restraint stress elevated the malondialdehyde (MDA) levels in mice's hippocampus, while pretreatment of animals with atorvastatin (10 mg/kg) could reverse it. The co-administration of melatonin and atorvastatin (10 mg/kg) increased the cortical superoxide dismutase (SOD) activity compared with atorvastatin alone, but could not alter the catalase (CAT) activity.

Conclusion: It is concluded that atorvastatin might augment the antidepressant-like properties of melatonin in FST.

Background: The primary phytoconstituents reported to have neuroprotective effects are flavonoids and phenolic compounds. Aerva persica roots are reported to be rich in flavonoids and phenolic compounds. Therefore, this study aimed to explore the nootropic potential of Aerva persica roots.

Objective: The objective of this study was to evaluate the nootropic potential of Aerva persica roots against D-galactose-induced memory impairment.

Methods: In this study, the roots of Aerva persica were extracted with 70% ethanol. The obtained extract was evaluated for total phenolic content using the Folin-Ciocalteu method and total flavonoid content using the aluminium chloride colorimetric assay. Afterward, the acute oral toxicity of the extract was determined following the Organisation for Economic Co-operation and Development (OECD) guideline 423. Additionally, two doses of Aerva persica (100 and 200 mg/kg body weight (BW)) were evaluated for their nootropic potential against D-galactose-induced memory impairment. The nootropic potential of the crude extract was assessed through a behavioural study and brain neurochemical analysis. Behavioural studies involved the evaluation of spatial reference- working memory using the radial arm maze test and the Y-maze test. Neurochemical analysis was performed to determine the brain's acetylcholine, acetylcholinesterase, glutathione (GSH), and malondialdehyde (MDA) levels.

Results: The total phenolic content and total flavonoid content were found to be 179.14 ± 2.08 μg GAE/mg and 273.72 ± 3.94 μg QE/mg, respectively. The Aerva persica extract was found to be safe up to 2000 mg/kg BW. Following the safety assessment, the experimental mice received various treatments for 14 days. The behavioural analysis using the radial maze test showed that the extract at both doses significantly improved spatial reference-working memory and reduced the number of total errors compared to disease control groups. Similarly, in the Y-maze test, both doses significantly increased the alteration percentage and the percentage of novel arm entry (both indicative of intact spatial memory) compared to disease control. In neurochemical analysis, Aerva persica at 200 mg/kg significantly normalised the acetylcholine level (p<0.0001) and GSH level (p<0.01) compared to disease control. However, the same effect was not observed with Aerva persica at 100 mg/kg. Additionally, Aerva persica at 200mg/kg BW significantly decreased the acetylcholinesterase level (p<0.0001) and decreased the brain's MDA level (p<0.01) compared to the disease control, whereas the effect of Aerva persica at 100 mg/kg BW in reducing acetylcholinesterase was non-significant.

Conclusion: Based on the results, it can be concluded that the nootropic potential of Aerva persica was comparable to that of the standard drug, Donepezil, and the effect might be attributed to