Systems pharmacology and experimental evaluation reveal pterocarpus mildbraedii's effects on behavioral changes, neuroinflammation, and oxidative stress in LPS-induced alzheimer's disease in rats

Background: Pterocarpus mildbraedii Harms (P. mildbraedii) was believed to have multiple benefits, including antioxidant, antipyretic, antalgic, anti-convulsant, and anxiolytic effects. People traditionally believe it can boost immunity, eliminate free radicals that cause cancer, protect the nervous system, and reduce inflammation. Previous studies have reported that Pterocarpus mildbraedii water extract (Pm) contained secondary metabolites able to cross the BBB. However, Pm's systemic mechanism and targets for neuroinflammation remain largely unexplored.

Aim of the study: This research used a systems pharmacology approach and experiment evaluation to reveal the potential protective effects of Pm against neuroinflammation, oxidative stress, and behavioral changes in an LPS-induced Alzheimer's disease (AD) rat model.

Materials and methods: This research integrated network pharmacology analysis and experimental verification to evaluate the potential pharmacological mechanism of PM against AD systematically. Swiss Target Prediction, GeneCards, and STRING databases were employed to identify potential AD targets. The interaction between active components and hub targets was confirmed via molecular docking. GO and KEGG pathway analyses were also carried out. Further, in vitro bioassays were used to explore Pm's anti-inflammatory and antioxidant activities and, finally, the in vivo potential of Pm against LPS-induced behavioral changes and neuroinflammatory and oxidative stress markers.

Results: Network pharmacology and molecular docking analysis revealed that Pm primarily regulates signaling proteins such as ESR1, ESR2, BACE1, MAPK1, TLR4, IL6, and GSK3B through active components like liquiritigenin and pterocarptriol. KEGG pathway analysis identified significant pathways for Pm's action against AD, including nitrogen metabolism and the VEGF signaling pathway. In vitro, bioassays demonstrated their anti-inflammatory and antioxidant properties, along with inhibitory effects on AchE and BchE. Behavioral tests showed that LPS exposure impaired exploratory behavior, spatial learning, and increased anxiety in rats, correlating with oxidative stress in the brain, marked by elevated MDA and NO levels, and decreased CAT, SOD, and GSH levels. LPS also raised TNF-α and IL-6 levels while reducing dopamine, serotonin, and AChE activity. Notably, Pm treatment significantly mitigated oxidative stress, improved behavioral activity, and restored neurotransmitter levels in LPS-induced Alzheimer's disease (AD) animals.