Natural products from selected medicinal plants as potential therapeutics in Alzheimer's disease

Dementia is a progressive neurological and degenerative syndrome that affects an individuals' memory, thinking, and social abilities severely enough to interfere with their daily lives. It is emerging as a public health priority in terms of the associated disability and mortality. Although there are several causes of dementia, Alzheimer's disease (AD) is the most common cause of progressive dementia in older adults. The initial AD presentations usually confine to social withdrawal, sleep, and personality disturbances. Later, these progress to short-term memory loss with orientation problems. Cognitive difficulties generally become evident toward the final stages of the disease. Much attention is now on various preventive and early-stage interventions that can delay the disease's progression. Acetylcholine esterase inhibitors and memantine remain the major drugs approved in AD. However, more robust evidence on the effectiveness of these drugs in managing AD and associated conditions are needed. The serious side effects of using these pharmaceutical agents are another concern that encourages patients to search for alternative approaches. Traditional systems of medicine, like Ayurveda, use several herbs and formulations to treat nervous system disorders. Herbal medicine is one such alternative, which has been in use for a long time to manage dementia and other cognitive dysfunctions. Many randomized controlled trials have reported the safety and effectiveness of herbal medicine in AD. Research studies show that many of these drugs possess antiinflammatory, antiapoptotic, and antioxidant actions. They prevent neuronal damage and suppress amyloid-β-induced oxidative stress and apoptosis. Herbal drugs contain phytoconstituents like alkaloids, tannins, polyphenols, terpenoids, and sterols with diverse pharmacological actions. Phytoconstituents with antioxidant, antiamyloidogenic, neuroprotective, antiinflammatory, and immunomodulatory activities can rejuvenate brain functions. They can also delay AD's neurodegenerative progression. Phenolic compounds and alkaloids are the two major classes of phytocompounds widely reported to be effective in various neurodegenerative conditions, including AD. Phenolic compounds like curcumin, epigallocatechin-3-gallate, and resveratrol work as neuroprotective bioactive components through their potent antioxidant and free radical scavenging properties. They also modify neuronal functions and offer neuroprotection by activating or inhibiting specific receptors or ion channels. Several alkaloid compounds improved neurotransmission in AD by inhibiting AchE. Long-term administration of alkaloid compounds like caffeine starting from an early age is reported to offer a protective role and reduce the risk of dementia/AD in later stages. Despite promising results in preclinical studies, many of these compounds fail to replicate the results in clinical studies due to poor bioavailability and constraints in metabolism. Research on developing novel potent phytocompounds for AD, which are effective and affordable with lesser side effects, is still ongoing worldwide. Liposome, intranasal, and nanoparticle-based drug delivery is also extensively studied to improve these drugs' therapeutic potential. Therefore, the proposed book chapter aims to precisely compile and present a few phenolic and alkaloid phytocompounds reported from selected medicinal plants to show promising results against AD pathogenesis.