Total Lignans From Leaves of Schisandra chinensis Improve Alzheimer's Disease Pathology Through the Nrf2/HO‐1/NLRP3 Pathway

Alzheimer's disease (AD) is a chronic neurodegenerative disorder, and activation of the NLRP3 inflammasome has been identified as one of the critical factors contributing to AD pathogenesis. Although previous studies have highlighted the neuroprotective effects of Schisandra chinensis lignans, it remains unclear whether total lignans extracted from the leaves of S. chinensis (TLS) can alleviate AD pathology by inhibiting the NLRP3 inflammasome. This study investigates the potential neuroprotective effects of TLS in streptozotocin (STZ)-induced AD rats and its associated signaling pathways. UHPLC-Orbitrap-MS was utilized to identify and characterize the major chemical constituents in the extract leaves of S. chinensis. Cognitive function was assessed using the Morris water maze (MWM) test, whereas Nissl staining, immunohistochemistry (IHC), biochemical assays, enzyme-linked immunosorbent assays (ELISA), and Western blot (WB) were utilized to analyze AD-related pathological changes and metabolic processes. The results demonstrated that TLS significantly ameliorates cognitive impairment and reduces the accumulation of phosphorylated tau (p-Tau). Further investigations revealed that TLS alleviates oxidative stress and inflammatory responses via modulation of the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/NLRP3 pathway. These findings suggest that TLS may hold potential therapeutic applications for AD.