Combined with UPLC-Triple-TOF/MS-based plasma lipidomics and molecular pharmacology reveals the mechanisms of schisandrin against Alzheimer’s disease

Abstract

Background Alzheimer’s disease (AD), a type of neurodegeneration disease, is characterized by Aβ deposition and tangles of nerve fibers. Schisandrin is one of the main components of Fructus Schisandrae Chinensis. Researches showed that schisandrin can improve the cognitive impairment and memory of AD mice, but the specific mechanism has not been fully elucidated. Purpose The purpose of this study is to investigate the possible mechanism of schisandrin in improving AD pathology. Methods The Morris water maze test was executed to detect spatial learning and memory. Ultra performance liquid chromatography-Triple time of flight mass spectrometry (UPLC-Triple-TOF/MS)-based plasma lipidomics was used to study the changes of plasma lipids. Moreover, we measured the levels of protein and mRNA expression of APOE and ABCA1 in the rat brains and in BV2 microglia. Results Our study found that schisandrin could improve learning and memory, and reduce Aβ deposition in AD rats. Furthermore, we found that schisandrin can improve plasma lipid metabolism disorders. Therefore, we hypothesized schisandrin might act via LXR and the docking results showed that schisandrin interacts with LXRβ. Further, we found schisandrin increased the protein and mRNA expression of LXR target genes APOE and ABCA1 in the brain of AD rats and in BV2 microglia. Conclusion Our study reveals the neuroprotective effect and mechanism of schisandrin improves AD pathology by activating LXR to produce APOE and ABCA1.

Research Progress on Natural Plant Molecules in Regulating the Blood–Brain Barrier in Alzheimer’s Disease

“…Previous studies have indicated that schisandrins possess antioxidative, anti-inflammatory, anti-fatigue, neurotransmitter regulation, anti-aging, and cardiovascular and cerebrovascular protection effects. Recent studies have shown that it can influence the progression of AD by modulating peripheral plasma lipid metabolism through the brain [247]. In a study by Li Q et al [248], it was discovered that schisandrin partially reversed neuronal apoptosis induced by Aβ, which is closely associated with the inhibition of NLRP1 inflammasome activation.…”