AI Assisted Mechanistic and Translational Evaluation of Triticum aestivum in Alzheimer’s disease: A Preclinical-to-Clinical Study

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by amyloid-β accumulation, tau hyperphosphorylation, oxidative stress, neuroinflammation, and synaptic dysfunction. extensive research, effective disease-modifying therapy remains limited. Wheatgrass (Triticum aestivum) has garnered attention as a rich source of bioactive phytochemicals, particularly apigenin, which exhibits antioxidant, anti-inflammatory, and neuroprotective properties. current evidence on the potential role of wheatgrass-derived apigenin in AD management, with an emphasis on its interaction with glycogen synthase kinase-3β (GSK-3β) and related signalling pathways. Available preclinical studies indicate that apigenin improves cognitive performance, reduces oxidative damage, suppresses inflammatory mediators, and attenuates tau phosphorylation and amyloidogenic processing. Mechanistically, its neuroprotective effects involve activation of the PI3K/Akt pathway, inhibition of GSK-3β, modulation of BDNF/CREB signalling, and preservation of neuronal integrity. Wheatgrass extract has also demonstrated memory-enhancing and anti-inflammatory effects in experimental models of cognitive impairment, suggesting that its therapeutic potential may extend beyond apigenin alone. However, the evidence remains preclinical, and issues such as low oral bioavailability, limited blood–brain barrier penetration, and metabolic instability continue to restrict clinical translation. Therefore, further pharmacokinetic optimization, standardized formulation development, and well-designed clinical studies are required to validate its efficacy in humans. Overall, wheatgrass-derived apigenin represents a promising natural candidate for multi-target intervention in AD.