Phytotherapeutics against Alzheimer's Disease: Mechanism, Molecular Targets and Challenges for Drug Development

Alzheimer's disease is inflating worldwide and is combatted by only a few approved drugs. At best, these drugs treat symptomatic conditions by targeting cholinesterase and N-methyl- D-aspartate receptors. Most of the clinical trials in progress are focused on developing disease-modifying agents that aim at single targets. The 'one drug-one target' approach is failing in the case of Alzheimer's disease due to its labyrinth etiopathogenesis. Traditional medicinal systems like Ayurveda use a holistic approach encompassing the legion of medicinal plants exhibiting multimodal activity. Recent advances in high-throughput technologies have catapulted the research in the arena of Ayurveda, specifically in identifying plants with potent anti-Alzheimer's disease properties and their phytochemical characterization. Nonetheless, clinical trials of very few herbal medicines are in progress. This review is a compendium of Indian plants and ayurvedic medicines against Alzheimer's disease and their paraphernalia. A record of 230 plants that are found in India with anti-Alzheimer's disease potential and about 500 phytochemicals from medicinal plants have been solicited with the hope of exploring the unexplored. Further, the molecular targets of phytochemicals isolated from commonly used medicinal plants, such as Acorus calamus, Bacopa monnieri, Convolvulus pluricaulis, Tinospora cordifolia and Withania somnifera, have been reviewed with respect to their multidimensional property, such as antioxidant, anti-inflammation, anti-aggregation, synaptic plasticity modulation, cognition, and memory-enhancing activity. In addition, the strengths and challenges in ayurvedic medicine that limit its use as mainstream therapy are discussed, and a framework for the development of herbal medicine has been proposed.