β‐Asarone Attenuates Neuroinflammation of Alzheimer's Disease by Activating Autophagy and Suppressing NLRP3 Inflammasome Assembly

ABSTRACT Aim Alzheimer's Disease (AD) is a neurodegenerative condition with poorly understood mechanisms and few effective treatments. β‐asarone has shown potential in AD management, though its molecular actions require further clarification. This study investigates the mechanisms through which β‐asarone exerts its effects using both animal and cellular models. Methods In vivo, the 3×Tg‐AD mice were administered β‐asarone for 8 weeks. Learning and memory abilities were assessed via the Morris water maze and step‐down tests. Histomorphological examination, immunofluorescence, immunohistochemistry, ELISA, transmission electron microscopy, and Western blotting were employed to detect pathological changes, neuroinflammation, and protein expression of relevant signaling pathway molecules. In vitro, Aβ was used to culture BV‐2 cells to mimic the brain microenvironment in Alzheimer's disease; changes in neuroinflammation, autophagy, and NLRP3 inflammasome‐related proteins were observed after treatment with β‐asarone. Results The administration of β‐asarone resulted in enhanced cognitive performance in 3×Tg‐AD mice, alongside a reduction in microglial apoptosis induced by Aβ. Additionally, β‐asarone diminished the accumulation of Aβ and phosphorylated Tau, ultimately supporting neuronal survival. In both the hippocampal tissue and BV‐2 cell models, treatment with β‐asarone led to a downregulation of neuroinflammatory markers and modulation of autophagy‐related proteins (Beclin‐1, P62, ATG5, LC3‐II/I), while concurrently suppressing components of the NLRP3 inflammasome (NLRP3, ASC, Caspase‐1, cleaved Caspase‐1). Notably, the autophagy inhibitor 3‐MA counteracted the inhibitory effects of β‐asarone on NLRP3 activation. Conclusion β‐Asarone attenuates AD‐related neuroinflammation by activating autophagy to inhibit NLRP3 inflammasome assembly.