Khan_2024_Neurochem.Int_179_105839

The intricate nature of Alzheimer's disease (AD) has presented significant hurdles in the development of effective interventions. Sulforaphane (SFN) is of interest due to its antioxidative, anti-inflammatory, and neuroprotective properties, which could address various aspects of AD pathology. This study explores the potential of SFN in a rat model of AD induced by Abeta (1-42) peptides. AD symptoms were triggered in rats by injecting Abeta (1-42) peptides directly into their cerebral ventricles. SFN (10 mg/kg and 20 mg/kg), Trigonelline (10 mg/kg), and Pioglitazone (10 mg/kg) were administered in Abeta (1-42) treated animals. Behavioral assessments were performed using the Novel Object Recognition tests. Various biochemical parameters, such as soluble Abeta (1-42), IRS-S312, GSK-3beta, TNF-alpha, acetylcholinesterase, nitrite levels, lipid peroxidation, and reduced glutathione activity, were quantified using ELISA kits and spectrophotometric assays. Histopathological analyses included Hematoxylin and Eosin, Crystal Violet, Congo red, and IRS-1 Immunohistochemistry staining. Quantification was performed to assess neuronal loss and Abeta plaque burden. The novelty of this study lies in its comprehensive evaluation of SFN's impact on multiple AD-related pathways at dual doses. The Novel Object Recognition test revealed that SFN, especially at higher doses, improved memory deficits induced by Abeta (1-42). Biochemically, SFN reduced hippocampal Abeta levels, IRS-S312, GSK-3beta, TNF-alpha, and acetylcholinesterase activity, while increasing glutathione levels, all in a dose-dependent manner. Histopathological analyses further confirmed SFN's protective role against Abeta-induced neuronal damage, amyloidosis, and changes in insulin signaling. These results highlight SFN's potential as a multifaceted therapeutic agent for AD, offering a promising avenue for treatment due to its antioxidative, anti-inflammatory, and neuroprotective properties. The inclusion of combination treatments with Trigonelline and Pioglitazone alongside SFN offers insights into potential synergistic effects, which could pave the way for developing combination therapies for AD.