Neuroprotective Effects of Tenoxicam and Phenethyl Isothiocyanate in an Aβ₁₋₄₂-Induced Rat Model of Alzheimer's Disease: Modulation of NF-κB/NLRP3 Signaling and Redox Homeostasis

作者：Kurmi S, Parab SB, Godad A, Waghmare P, Doshi G · 发表于：Molecular neurobiology · 年份：2026 · DOI：10.1007/s12035-026-06037-x · 研究领域：Alzheimer Disease、NF-kappa B、Isothiocyanates、Piroxicam、Signal Transduction、Neuroprotective Agents、NLR Family, Pyrin Domain-Containing 3 Protein、Homeostasis、Animals、Amyloid beta-Peptides、Male、Rats, Wistar

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, neuroinflammation, oxidative stress, and amyloid pathology, yet effective disease-modifying therapies remain limited. This study asked whether combined targeting of inflammatory and oxidative stress pathways could offer enhanced neuroprotection in an Aβ1-42-induced rat model of AD. Tenoxicam, an oxicam-class non-steroidal anti-inflammatory drug with COX-linked anti-inflammatory activity, and phenethyl isothiocyanate (PEITC), a natural compound known for antioxidant and Nrf2-activating properties, were selected on the basis of their complementary mechanisms; however, their combined potential in this model has not been sufficiently explored, providing the rationale for this hypothesis-driven investigation. Male Wistar rats were assigned to control, disease, standard, tenoxicam, PEITC, and combination treatment groups. Cognitive performance was evaluated using the Morris Water Maze, Y-maze, and Novel Object Recognition tests, while neuroinflammatory and oxidative stress markers, including NF-κB, NLRP3, IL-1β, Nrf2, catalase, and malondialdehyde, were assessed alongside histopathological examination of hippocampal integrity and molecular docking against COX-2, NF-κB, and NLRP3. Aβ1-42 administration induced significant cognitive impairment, neuroinflammation, oxidative stress, and neuronal damage. Tenoxicam and PEITC improved behavioral performance, reduced inflammatory signal...