Lawal Akeem Olalekan, Agboola Olaoluwa Oladimeji, Akinjiyan Moses Orimoloye, Ijatuyi Taiwo Tolulope, Dahunsi Damilola Timothy, Okeowo Oritoke Modupe, Folorunso Ibukun Mary, Olajuyigbe Olakunle Julius, Elekofehinti Olusola Olalekan
Molecular Biology Unit, Department of Biochemistry, Federal University of Technology, Akure, Ondo State, Nigeria.
Precision Molecular Laboratory, Akure, Ondo State, Nigeria.
Mol Neurobiol. 2025 Mar 20. doi: 10.1007/s12035-025-04839-z.
Artificial sweeteners' neurotoxicity remains a significant health concern. This study investigated the neurotoxic effects of aspartame (ASP) and evaluated the neuroprotective potential of Tetrapleura tetraptera ethanol extract (TT) in Wistar rats. Thirty male rats were grouped into six (n = 5) and some received oral ASP administration for 14 days, with some groups post-treated with TT (200 and 400 mg/kg) orally for 14 days. Neurotransmitter function, oxidative stress markers, inflammatory mediators, and apoptotic parameters were assessed using biochemical assays and RT-PCR on serum and brain tissues after the sacrifice. ASP significantly (p < 0.001) increased AChE and BChE activities while decreasing dopamine levels. RT-PCR analysis revealed that ASP upregulated pro-inflammatory genes (TNF-α, IL-6, IL-1β) and pro-apoptotic markers (BAX, CASP3, CASP9, P53) while downregulating anti-apoptotic BCL-2 gene expression. ASP also reduced antioxidant levels (GSH, GCL), elevated S100B level and activated cAMP/PKA signalling. TT post-treatment significantly (p < 0.001) reversed these alterations, reducing MDA and GSSG levels while enhancing GSH/GSSG ratio and antioxidant activities. TT markedly downregulated inflammatory markers and upregulated IL-10 expression. Histopathological examination suggests TT's protective effects against ASP-induced neural damage. These findings indicate that TT exhibits neuroprotective properties through its antioxidant, anti-inflammatory, and anti-apoptotic activities against ASP-induced neurotoxicity.
人工甜味剂的神经毒性仍然是一个重大的健康问题。本研究调查了阿斯巴甜（ASP）的神经毒性作用，并评估了四棱豆乙醇提取物（TT）对Wistar大鼠的神经保护潜力。将30只雄性大鼠分为六组（n = 5），一些大鼠接受为期14天的口服ASP给药，部分组在给药后再口服TT（200和400mg/kg）14天。在处死大鼠后，使用生化分析和RT-PCR对血清和脑组织中的神经递质功能、氧化应激标志物、炎症介质和凋亡参数进行评估。ASP显著（p < 0.001）增加了乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）的活性，同时降低了多巴胺水平。RT-PCR分析显示，ASP上调了促炎基因（TNF-α、IL-6、IL-1β）和促凋亡标志物（BAX、CASP3、CASP9、P53），同时下调了抗凋亡BCL-2基因的表达。ASP还降低了抗氧化水平（谷胱甘肽（GSH）、谷氨酸半胱氨酸连接酶（GCL）），升高了S100B水平并激活了环磷酸腺苷/蛋白激酶A（cAMP/PKA）信号通路。TT给药后显著（p < 0.001）逆转了这些改变，降低了丙二醛（MDA）和氧化型谷胱甘肽（GSSG）水平，同时提高了谷胱甘肽/氧化型谷胱甘肽（GSH/GSSG）比值和抗氧化活性。TT显著下调了炎症标志物并上调了白细胞介素-10（IL-10）的表达。组织病理学检查表明TT对ASP诱导的神经损伤具有保护作用。这些发现表明，TT通过其抗氧化、抗炎和抗凋亡活性对ASP诱导的神经毒性表现出神经保护特性。
