Computational and Experimental Validation of Anti-LPS-Induced Alzheimer’s Disease Effects of <i>Pterocarpus mildbraedii</i> and its Compounds: Combining Network Pharmacology, Molecular Docking, <i>In Vitro</i> , and <i>In Vivo</i> Approaches

Pterocarpus mildbraedii(Pm) harms is traditionally valued for its antioxidant, analgesic, anxiolytic, and neuroprotective properties. Some of its active metabolites can cross the BBB, are believed to enhance immunity and reduce inflammation, yet its specific effects on neuroinflammation remain underexplored. This study investigates Pm’s neuroprotective potential in a lipopolysaccharide (LPS)-induced rat model of Alzheimer’s disease (AD). Potential AD-related targets were identified using Swiss Target Prediction, GeneCards, and STRING databases. Molecular docking confirmed strong interactions between key Pm constituents, such as liquiritigenin and pterocarptriol, and critical proteins including ESR1, ESR2, BACE1, and MAPK1. GO and KEGG analyses revealed relevant pathways, including nitrogen metabolism and VEGF signaling. In vitro, Pm exhibited potent antioxidant and anti-inflammatory effects, along with inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). In vivo, Pm significantly attenuated LPS-induced oxidative stress and neuroinflammation, evidenced by reduced malondialdehyde (MDA) and nitric oxide (NO), and restoration of antioxidant enzymes (CAT, SOD, GSH). Behavioral assessments showed improvements in spatial learning, exploratory activity, and anxiety-like behaviors. Overall, these findings highlight Pterocarpus mildbraedii as a promising phytotherapeutic candidate for AD, capable of mitigating behavioral deficits, oxidative stress, and neuroinflammatory responses.