Moringa oleifera neuroprotective mechanisms reviewed, showing potential for Alzheimer's disease therapy

Alzheimer's disease (AD) is a devastating neurodegenerative disorder marked by progressive cognitive decline, memory loss, and tau hyperphosphorylation. Current pharmacological treatments primarily offer symptomatic relief, failing to halt or reverse the underlying disease progression. This gap necessitates exploring novel therapeutic avenues, including natural compounds. Moringa oleifera (M.O.), a plant rich in diverse phytochemicals, is being investigated for its potential to address the multifaceted pathology of AD through its antioxidant and anti-inflammatory properties.

This review systematically analyzed existing literature on Moringa oleifera's neuroprotective effects in Alzheimer's disease models. It synthesized findings from various in vivo and in vitro studies, focusing on the plant's phytochemical composition and their impact on key AD pathologies. The authors explored how Moringa's bioactives, including flavonoids (Quercetin, kaempferol), phenolic acids, alkaloids, and isothiocyanates, modulate oxidative stress, inflammation, and amyloid-beta processing, drawing conclusions on its therapeutic potential based on reported mechanisms.

The review identified multiple neuroprotective mechanisms attributed to Moringa oleifera phytochemicals. These bioactives prevent oxidative neuronal damage by directly scavenging free radicals and potently inhibiting the release of proinflammatory cytokines by blocking the NF-κB pathway. Isothiocyanates, specifically, were reported to activate the Nrf2/ARE system, leading to the upregulation of cytoprotective enzymes and promotion of brain endogenous antioxidant defenses. In in vivo AD models, Moringa extracts demonstrated anti-AchE activity, improving cholinergic transmission. They also reduced Aβ levels and enhanced cognitive performance. The proposed modus operandi includes:

Inhibition of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) activity and direct inhibition of Aβ peptide aggregation into neurotoxic oligomers. Furthermore, Moringa functions as a modulator of mitochondrial activity, increasing the activity of endogenous antioxidant enzymes like superoxide dismutase (SOD) and catalase, thereby enhancing neuronal energy metabolism while attempting to block apoptosis.