A Review on Neuroprotective Activity and Pharmacological Mechanisms of Bacopa monnieri in Various Animal Models of Alzheimer's Disease

Review Article

Abstract

Alzheimer's disease is a progressive neurodegenerative condition characterized by complex multifactorial neuropathology, including amyloid-beta aggregation, tau hyperphosphorylation, oxidative stress, cholinergic deficits, and neuroinflammation. Bacopa monnieri and its bioactive dammarane-type triterpenoid saponins display multifaceted neuroprotective actions across transgenic, naturally aged, invertebrate, and neurotoxin-induced experimental models. An evaluation of these experimental models shows that Bacopa monnieri exerts polypharmacological effects by suppressing soluble amyloid-beta accumulation, downregulating glycogen synthase kinase-3 beta (GSK-3β) activity to decrease tau hyperphosphorylation, upregulating the Nrf2/HO-1 antioxidant pathway, inhibiting nuclear factor kappa B (NF-κ B)-driven inflammatory cascades, and stabilizing central cholinergic transmission through acetylcholinesterase inhibition. Additional structural and functional benefits include the enhancement of hippocampal neurogenesis and synaptic plasticity. Despite these consistent preclinical findings, barriers remain due to extract composition variability, a predominant focus on prophylactic rather than therapeutic treatment paradigms, male-biased animal cohorts, and limited pharmacokinetic profiling. Extract standardization and evaluating therapeutic intervention windows in clinically representative models are the main requirements for advancing this botanical candidate toward clinical validation