The Antioxidative, Anti-inflammatory and Anti-apoptotic Effects of Tetrapleura Tetraptera (Aidan) Ethanol Leaf Extract in the Brain of Wistar Rats Exposed to Aspartame.

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.