Program in Biochemistry and Bioprospection, Laboratory of Neurochemistry, Inflammation and Cancer, Center for Chemical, Pharmaceutical and Food Sciences, Federal University of Pelotas, University Campus, Pelotas, RS, Brazil.
Program in Biochemistry and Bioprospecting, Laboratory of Chemistry Applied to Bioactives, Center for Chemical, Pharmaceutical and Food Sciences, Federal University of Pelotas, University Campus S/N, Pelotas, RS, Brazil.
Brain Res Bull. 2023 Feb;193:1-10. doi: 10.1016/j.brainresbull.2022.11.015. Epub 2022 Nov 25.
Alzheimer's disease (AD) is characterized mostly by memory decline. The current therapeutic arsenal for treating AD is limited, and the available drugs only produce symptomatic benefits, but do not stop disease progression. The search for effective therapeutic alternatives with multitarget actions is therefore imperative. One such a potential alternative is thiazolidin-4-one, a compound that exhibits anti-amnesic, anticholinesterase, and antioxidant activities. The aim of this study was evaluated the effects of 2-(4-(methylthio)phenyl)- 3-(3-(piperidin-1-yl)propyl) thiazolidin-4-one (DS12) on memory and neurochemical parameters in a model of AD induced by an intracerebroventricular injection of streptozotocin (STZ). Adult male rats were divided into five groups: I, control (saline); II, DS12 (10 mg/kg); III, STZ; IV, STZ + DS12 (10 mg/kg); V, STZ + donepezil (5 mg/kg). The rats were orally treated with DS12 and donepezil for a period of 20 days. Memory, acetylcholinesterase (AChE) activity, phosphorylated tau protein levels and oxidative stress were analyzed in the cerebral cortex, hippocampus, and cerebellum. Biochemical and hematological parameters were evaluated in the blood and serum. Memory impairment and the increase in AChE activity and phosphorylated tau protein level induced by STZ were prevented by DS12 and donepezil treatment. Streptozotocin induces an increase in reactive oxygen species levels and a decrease in catalase activity in the hippocampus, cerebral cortex, and cerebellum. DS12 treatment conferred protection from oxidative alterations in all brain structures. No changes were observed in serum biochemical parameters (glucose, triglycerides, cholesterol, uric acid, and urea) or hematological parameters, such as platelets, lymphocytes, hemoglobin, hematocrit, and total plasma protein. DS12 improved memory and neurochemical changes in an AD model and did not show toxic effects, suggesting the promising therapeutic potential of this compound.
阿尔茨海默病（AD）的主要特征是记忆下降。目前用于治疗 AD 的治疗方法有限，现有的药物只能产生对症治疗的效果，但并不能阻止疾病的进展。因此，寻找具有多靶点作用的有效治疗替代方法势在必行。噻唑烷-4-酮就是这样一种有潜力的替代药物，它具有抗健忘、抗胆碱酯酶和抗氧化作用。本研究旨在评估 2-(4-(甲硫基)苯基)-3-(3-(哌啶-1-基)丙基)噻唑烷-4-酮（DS12）对脑室注射链脲佐菌素（STZ）诱导的 AD 模型中记忆和神经化学参数的影响。成年雄性大鼠分为五组：I，对照组（生理盐水）；II，DS12（10mg/kg）；III，STZ；IV，STZ+DS12（10mg/kg）；V，STZ+多奈哌齐（5mg/kg）。大鼠连续 20 天口服给予 DS12 和多奈哌齐。在大脑皮质、海马和小脑分析记忆、乙酰胆碱酯酶（AChE）活性、磷酸化 tau 蛋白水平和氧化应激。在血液和血清中评估生化和血液学参数。DS12 和多奈哌齐治疗可预防 STZ 引起的记忆障碍以及 AChE 活性和磷酸化 tau 蛋白水平的升高。链脲佐菌素诱导海马、大脑皮质和小脑中活性氧水平升高，过氧化氢酶活性降低。DS12 治疗可防止所有脑结构的氧化改变。血清生化参数（葡萄糖、甘油三酯、胆固醇、尿酸和尿素）或血液学参数（血小板、淋巴细胞、血红蛋白、红细胞压积和总血浆蛋白）无变化。DS12 改善了 AD 模型中的记忆和神经化学变化，且没有表现出毒性作用，这表明该化合物具有有前途的治疗潜力。
