Hyptis suaveolens-Mediated Silver Nanoparticles reversed Aluminum Chloride-Induced Cerebellar toxicity via modulation of oxidative stress, Neuroinflammation, and Neuronal Integrity

Abstract Background Aluminum chloride (AlCl₃) exposure has been implicated in neurotoxicity through mechanisms involving oxidative stress, neuroinflammation, and neuronal degeneration, particularly within the cerebellum. Green synthesis of silver nanoparticles using medicinal plants has gained attention for their potential neuroprotective properties. This study investigated the protective effects of Hyptis suaveolens -mediated silver nanoparticles (HS-AgNPs) against AlCl₃-induced cerebellar toxicity in rats. Methods Silver nanoparticles were synthesized using Hyptis suaveolens leaf extract and characterized using standard physicochemical techniques. Adult Wistar rats were randomly divided into experimental groups, including control, AlCl₃-treated, and AlCl₃ + HS-AgNP-treated groups. Aluminum chloride was administered to induce cerebellar toxicity, while HS-AgNPs were given as therapeutic intervention. Biochemical assays were performed to assess oxidative stress markers, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH). Pro-inflammatory markers were evaluated to determine neuroinflammatory responses. Histopathological examination of cerebellar tissue was conducted to assess neuronal integrity. Results AlCl₃ exposure significantly increased lipid peroxidation and pro-inflammatory markers while reducing antioxidant enzyme activities compared to controls. Histological analysis revealed neuronal degeneration, disrupted Purkinje cell layers, and structural alterations in the cerebellum. Treatment with HS-AgNPs significantly reduced oxidative stress, restored antioxidant enzyme levels, attenuated neuroinflammation, and preserved cerebellar architecture. The reversal of biochemical and histological alterations suggests a protective role of HS-AgNPs. Conclusion Hyptis suaveolens -mediated silver nanoparticles exhibit significant neuroprotective effects against aluminum-induced cerebellar toxicity by modulating oxidative stress and inflammatory pathways while preserving neuronal integrity. These findings support the therapeutic potential of plant-mediated nanoparticles in managing environmentally induced neurotoxicity and warrant further translational investigation.