Flavonoids from Liriodendron chinense Leaves Alleviate Oxidative Activity in Vitro and D-galactose-induced Brain Injury via AMPK/SIRT1 Pathway in Vivo

The exploration of active ingredients and new activities of industrial crops could expand their scope of applications. Liriodendron chinense (L. chinense), an important ornamental and economic forest tree in China, has been widely used in timber, medicine and landscape. Flavonoids are major constituents of L. chinense leaves, while their effects of preventing brain damage are still unclear. In this study, flavonoids from L. chinense leaves (LCLF) were obtained through AB-8 resin chromatography and UPLC-MS/MS assay indicated that 16 compounds were identified from LCLF. LCLF treatment showed significant scavenging activities against DPPH•, ABTS•+, •OH, FRAP and total reducing power. D-galactose-impaired exploratory behaviors, cognitive functions and histopathological alterations in hippocampus of mice were obviously recovered by LCLF administration. Network pharmacology results demonstrated that LCLF could produce the healing efficacy through multiple pathways, mostly related to oxidative stress and inflammation. Further in vivo experiments revealed that LCLF treatment could regulated MDA content, SOD, CAT and GSH-Px activity, as well as the production of inflammatory factors (NO, IL-1β and IL-6). The underlying mechanisms of LCLF were probably related to Nrf2/HO-1, NF-κB and AMPK/SIRT1 pathways. Molecular docking results and surface plasmon resonance analysis validated that especially hesperidin in LCLF had strong binding activities with all 8 genes in the mentioned pathways. Our study revealed the beneficial effects of LCLF on oxidative activity and D-galactose-induced brain injury, offering experimental support for its potential application in pharmaceutical and other industries.