Integrating network pharmacology and in vivo study to explore the anti-Alzheimer's potential of Bergenia ligulata and Nelumbo nucifera.

Abstract

Amyloid plaque buildup, tau protein tangles, oxidative stress, and neuronal death are the hallmarks of Alzheimer's disease (AD). Using network pharmacology, molecular docking, and in vivo experiments, this study investigated the neuroprotective potential of Bergenia ligulata (BL) and Nelumbo nucifera (NN) against aluminum chloride (AlCl₃)-induced AD. Network pharmacology focused on important biomarker proteins like acetylcholinesterase (AChE), BCL2, and caspase-3 to identify 74 bioactive targets linked to AD. The evaluation of ligand-protein interactions was done using molecular docking. Male Wistar rats were exposed to AlCl₃ to cause AD-like pathology in vivo, and a combination treatment of BL and NN at varying doses was provided. Apoptosis markers (BCL2, caspase-3), biochemical investigations (AChE activity, oxidative stress markers-GSH, SOD, catalase, and lipid peroxidation), behavioral evaluations (elevated plus maze, conditioned avoidance test), and histopathological analyses were investigated. The combination of BL and NN demonstrated substantial neuroprotection in a dose-dependent manner. Reduced AChE levels point out improved cholinergic activity. Oxidative stress indicators showed improvement, with lower levels of malondialdehyde and higher anti-oxidant levels of GSH, SOD, and catalase. Apoptotic markers showed an increase in BCL2 expression and a decrease in caspase-3, suggesting anti-apoptotic effects. Reduced neuronal degeneration in the cortex and hippocampal regions was confirmed by histopathology of the brain. The synergistic potential of BL and NN demonstrated potent neuroprotective effects by modulating AChE activity, reducing oxidative stress, increasing anti-oxidant levels, and inhibiting apoptosis. These findings highlighted the potential of BL and NN as a new therapeutic approach for the AD.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-025-04274-w.