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3-(3-(二乙氨基)丙基)-2-(4-(甲硫基)苯基)噻唑烷-4-酮减轻东莨菪碱诱导的大鼠认知障碍:对神经保护作用的见解

3-(3-(diethylamino)propyl)-2-(4-(methylthio)phenyl)thiazolidin-4-one Attenuates Scopolamine-induced Cognitive Impairment in Rats: Insights Into Neuroprotective Effects.

作者信息

de Souza Anita Avila, Goularte Kelen Cristiane Machado, Piccoli Raphaela Cassol, Custódio Solange Vega, de Mello Julia Eisenhardt, Victor Melinda Gomes, Domingues William Borges, de Souza Lucas Petitemberte, Dos Santos Gonçalves Laís, Campos Vinicius Farias, Cunico Wilson, Oses Jean Pierre, Stefanello Francieli Moro, de Aguiar Mayara Sandrielly Soares, Spanevello Roselia Maria

机构信息

Graduate Program in Biochemistry and Bioprospection - Laboratory of Neurochemistry, Inflammation, and Cancer - Center the Chemical, Pharmaceutical, and Food Sciences, Federal University of Pelotas, Capão Do Leão Campus S/N, Pelotas-RS, CEP 96010‑900, Brazil.

Graduate Program in Biochemistry and Bioprospecting - Laboratory of Chemistry Applied to Bioactive - Center the Chemical, Pharmaceutical and Food Sciences, Federal University of Pelotas, Capão Do Leão Campus S/N, Pelotas-RS, CEP 96010‑900, Brazil.

出版信息

Mol Neurobiol. 2025 Mar 31. doi: 10.1007/s12035-025-04887-5.

Abstract

Alzheimer's Disease (AD) is characterized by memory decline, dysregulation in cholinergic and purinergic signaling, neuroinflammation, and oxidative stress. Current treatments are limited, highlighting the need for new compounds to prevent or delay AD progression. Thiazolidinones have emerged as promising candidates due to their antioxidant, anti-inflammatory, and anticholinesterase properties. The aim of this study was to evaluate the effects of 3-(3-(diethylamino)propyl)-2-(4-(methylthio)phenyl)thiazolidin-4-one (DS27) in a rat model of scopolamine-induced memory deficits. Male rats were divided into groups: I - Control, II - Scopolamine (SCO) (1 mg/kg), III - SCO and DS27 (5 mg/kg), IV - SCO and DS27 (10 mg/kg), V - SCO and donepezil (5 mg/kg). The animals were treated orally with DS27 or donepezil for seven days. On the 8th day, they underwent the open field test and inhibitory avoidance training, followed by intraperitoneal administration SCO. Twenty-four hours later, an inhibitory avoidance test was conducted. Acetylcholinesterase (AChE) activity, oxidative stress, and inflammatory and purinergic parameters were analyzed in the cerebral cortex, hippocampus, cerebrospinal fluid, serum, lymphocytes, and liver. DS27 prevented memory deficits, alterations in AChE activity, and oxidative damage induced by SCO in brain structures. Additionally, DS27 prevented SCO-induced decrease in IL-10 levels, and increase in IL-6, and TNF-α expression in the cerebral cortex, and normalized ATP and ADP hydrolysis in cerebrospinal fluid and lymphocytes. DS27 did not induce oxidative stress in the liver or alter serum biochemical parameters. These findings suggest that DS27 has significant neuroprotective properties and could be a promising alternative for treating neurodegenerative diseases like AD.

摘要

阿尔茨海默病(AD)的特征为记忆衰退、胆碱能和嘌呤能信号传导失调、神经炎症以及氧化应激。目前的治疗方法有限,这凸显了开发新化合物以预防或延缓AD进展的必要性。噻唑烷酮因其抗氧化、抗炎和抗胆碱酯酶特性而成为有前景的候选药物。本研究的目的是评估3-(3-(二乙氨基)丙基)-2-(4-(甲硫基)苯基)噻唑烷-4-酮(DS27)对东莨菪碱诱导的大鼠记忆缺陷模型的影响。雄性大鼠被分为几组:I组 - 对照组,II组 - 东莨菪碱(SCO)(1 mg/kg)组,III组 - SCO与DS27(5 mg/kg)组,IV组 - SCO与DS27(10 mg/kg)组,V组 - SCO与多奈哌齐(5 mg/kg)组。动物口服DS27或多奈哌齐,持续7天。在第8天,它们接受旷场试验和抑制性回避训练,随后腹腔注射SCO。24小时后,进行抑制性回避试验。分析了大脑皮层、海马体、脑脊液、血清、淋巴细胞和肝脏中的乙酰胆碱酯酶(AChE)活性、氧化应激以及炎症和嘌呤能参数。DS27可预防记忆缺陷、AChE活性改变以及SCO在脑结构中诱导的氧化损伤。此外,DS27可预防SCO诱导的大脑皮层中IL-10水平降低以及IL-6和TNF-α表达增加,并使脑脊液和淋巴细胞中的ATP和ADP水解恢复正常。DS27不会在肝脏中诱导氧化应激,也不会改变血清生化参数。这些发现表明,DS27具有显著的神经保护特性,可能是治疗AD等神经退行性疾病的有前景的替代药物。

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