Network Pharmacology and Molecular Docking-Based Evaluation of Bacopa monnieri for Neuroprotection in Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that leads to memory loss, cognitive decline, and eventually functional impairment; neuropathological features include extracellular amyloid-β (Aβ) plaque deposition and intracellular neurofibrillary tangles of hyperphosphorylated tau in addition to synaptic dysfunction and significant neuronal cell death. Currently approved therapies include acetylcholinesterase inhibitors and the NMDA receptor antagonist memantine, which offer only modest symptomatic benefits and limited effects on pathophysiological mechanisms within AD, indicating an urgent need for multi-target disease-modifying approaches. Bacopa monnieri (L.) Wettst. (Brahmi), An ancient Ayurvedic nootropic, it emerged as a potent neuroprotective agent due to its broad-based profile of phytoconstituents, such as triterpenoid saponins (bacosides) and flavonoids, with antioxidant, anti-inflammatory, anti-amyloidogenic, and neurogenic activity. Biotechnological approaches such as network pharmacology and molecular docking are increasingly significant for exploring the multi-component, multi-target nature of herbal medicines like B. monnieri in complex disease systems like AD. This review provides a comprehensive overview on the possible neuroprotective role of B. monnieri in AD using network pharmacological and molecular docking-based approaches to further evaluate potential therapeutic targets. We overview AD pathophysiology and the ethnomedicinal and pharmacological background of B. monnieri, summarize its phytochemistry and pharmacokinetics, and critically appraise in vitro, in vivo and clinical evidence for cognitive- and neuroprotection effects. We then outline the principles and workflows of network pharmacology and docking as they apply to B. monnieri, review key studies that dock bacosides and related compounds against BACE1, cholinesterases, tau kinases, inflammatory mediators, and neurotransmitter receptors with experimental data when available. Combined analysis suggests that the constituents of B. monnieri can modulate multiple pathways associated with AD, such as PI3K/Akt, MAPK, and NF-κB signaling and neurotrophin signaling pathways, along with cholinergic synapse function and Aβ production through inhibition of BACE1 activity, while providing antioxidant effects, regulating inflammation, and supporting synaptic plasticity. Yet considerable gaps still exist, notably between brain bioavailability of active metabolites, quantitative target engagement in vivo and strong clinical evidence in AD populations. Such postulates, in conjunction with rigorous multi-omics-driven network pharmacology, better in vitro and in vivo models, rational formulation strategy, and biomarker-rich clinical trials, will be necessary for translating the traditional usage and pre-clinical therapeutic potential of B. monnieri into an evidence-based neuroprotective therapy against AD.