The Role of Natural Products in the Discovery of New Drug Candidates for the Treatment of Neurodegenerative Disorders II: Alzheimers Disease

Abstract

The present review is part II in a series (part I focuses on Parkinson's Disease) that addresses the value of natural product chemistry in the discovery of medicines for the treatment of neurodegenerative disorders. Data reviewed document that a host of products from plant species and derivatives have neuroprotectant effects in vitro and in vivo. In addition, besides neuroprotection, natural products also demonstrate biological effects that target biochemical pathways underlying associated symptoms of neurdegnerative disorders that include cognitive impairments, energy/fatigue, mood, and anxiety. This part of the review series focuses specifically upon Alzheimer's Disease (AD). AD is postulated to result from extracellular formation of amyloid plaques and intracellular deposits of neurofibrilary tangles in the hippocampus, cerebral cortex and other areas of the brain essential for cognitive function. Plaques are formed mostly from the deposition β-amyloid (Aβ), a peptide derived from the amyloid precursor protein (APP). Filamentous tangles are formed from paired helical filaments composed of neurofilament and hyperphosphorilated tau protein, a microtubule-associated protein. In addition, environmental factors can engender the production of cytokines that are closely related to the installation of an inflammatory process that contributes to neuronal death and the development and the progression of AD. In this review we focus on the recent main contribuitions of natural products chemistry to the discovery of new chemical entities usefull to the control and prevention of AD installation and progression. More than sixteen plant species, including Ginseng, Celastrus paniculatus, Centella asiatica, Curcuma longa, Ginkgo biloba, Huperzia serrata, Lycoris radiate, Galanthus nivalis, Magnolia officinalis, Polygala tenuifolia, Salvia lavandulaefolia, Salvia miltiorrhiza, Coptis chinensis, Crocus sativus, Evodia rutaecarpa, Sanguisorba officinalis, Veratrum grandiflorum and Picrorhiza kurvoa, are discussed as potential sources of active extracts. In addition, more than sixty secondary metabolites are under evaluation for their efficacy on controlling symptoms and to impede the development and progression of AD.

Herbs to curb cyclic nucleotide phosphodiesterase and their potential role in Alzheimer’s disease

“…Recently, natural plants extracts and their bio-active compounds has also been demonstrated to moderate the levels of cyclic nucleotide through inhibition of phosphodiesterases (Rahimi et al, 2010). In recent years, there is an unprecedented development in herbal medicines and these are gaining popularity day by day for the treatment of various neurodegenerative disorders including Alzheimer's disease (Divino da Rocha et al, 2011;Howes and Houghton, 2003;Shu, 1998). Herbal PDE inhibitors are under clinical development for the treatment of Alzheimer's disease.…”

“…During last decade various pharmaceutically active compounds/extracts come from the plants origin and shown beneficial effect in treatment of Alzheimer's disease and other cognitive disorders (Currais et al, 2014;Divino da Rocha et al, 2011).…”

Ayurvedic medicinal plants for Alzheimer's disease: a review

“…CP extracts also protected neuronal cells against glutamate-induced toxicity by modulating glutamate receptor function. In addition, the CP extracts protected neuronal cells by virtue of their free radical scavenging properties, reducing lipid peroxidation, and also by their ability to induce the antioxidant enzyme catalase [68,72-75]. In addition, aqueous extracts of CP seed have dose-dependent cholinergic activity, thereby improving memory performance [68].…”

Natural Products As A Rich Source Of Tau-Targeting Drugs For Alzheimer’s Disease

“…Several natural products already evaluated for their efficacy in treating AD have been previously been summarized in literature [45,46]. Since recent clinical trials suggested tau-based therapies may be more effective than anti-Aβ treatments for patients already presenting AD symptoms, the relative paucity of tau-reducing agents needs to be addressed.…”