Role of Galangin for the Treatment of Alzheimer’s Disease: Journey So Far and Road Ahead

Purpose of Review: Alzheimer’s disease (AD) is a progressive neurodegenerative disease (NDs) that primarily affects cognitive function, with memory loss, impaired judgment, and difficulties in learning and language being prevalent among affected individuals. Currently available treatments, such as parasympathomimetic drugs, N-methyl-D-aspartate (NMDA) glutamate receptor antagonists, and monoclonal antibodies, only provide symptomatic relief. However, they are associated with side effects on long-term use. Hence, a safe and effective treatment can be achieved using plant-based bioactives such as galangin (GAL). Recent Findings: Among them, GAL, a flavonol, deciphers potent neuroprotective effects. GAL possesses anti-amyloid, antitau, antioxidant, anti-inflammatory, and anti-cholinesterase effects. Moreover, it also attenuates mitochondrial dysfunction and neuronal cell apoptosis. Despite showing such neuroprotective effects, GAL shows a low dissolution profile, leading to poor bioavailability of the drug in the brain. In the last few decades, novel drug delivery systems (NDDS) have shown significant responses to overcome the limitations of conventional delivery of lipophilic drugs. Nanoformulations exhibit many advantages such as easy preparation, high drug loading, high stability, enhanced loaded drug efficacy, and better drug delivery at the target site. Several databases have been searched, such as Sciencedirect, Pubmed, Google Scholar, with the keywords “galangin”, “Alzheimer’s disease”, and “Nanoformulation”. Among them, 200 articles were found relevant to the proposed study, where 146 selective articles were referred for preparing the manuscript. Summary: The present review has entailed about the mechanism through which GAL shows a neuroprotective role in treating AD. However, NDDS loaded with GAL has shown significant benefits over conventional oral administration. Despite having promising potential of GAL against NDs in its naïve form as well as in the form of nanoformulations, its translation into a marketed product is limited due to stability and scalability. A better understanding of mechanistic pathways and integrity of drug-loaded nanoformulations within the biological fluids, as well as analyzing the challenges at the BBB interface related to permeation and site specificity, would offer a translational nanomedicine of GAL for treating NDs, especially AD.