Plant-derived compounds and neurodegenerative diseases: Different mechanisms of action with therapeutic potential

Neurodegenerative diseases are a group of disorders characterized by progressive degeneration of discrete groups of neurons causing severe disability. The main risk factor is age, hence their incidence is rapidly increasing worldwide due to the rise in life expectancy. Although the causes of the disease are not identified in about 90% of the cases, in the last decades there has been great progress in understanding the basis for neurodegeneration. Different pathological mechanisms including oxidative stress, mitochondrial dysfunction, alteration in proteostasis and inflammation have been addressed as important contributors to neuronal death. Despite our better understanding of the pathophysiology of these diseases, there is still no cure and available therapies only provide symptomatic relief. In an effort to discover new therapeutic approaches, natural products have aroused interest among researchers given their structural diversity and wide range of biological activities. In this review, we focus on three plant-derived compounds with promising neuroprotective potential that have been traditionally used by folk medicine: the flavonoid quercetin (QCT), the phytocannabinoid cannabidiol (CBD)and the tryptamine N,N-dimethyltryptamine (DMT). These compounds exert neuroprotective effects through different mechanisms of action, some overlapping, but each demonstrating a principal biological activity: QCT as an antioxidant, CBD as an anti-inflammatory, and DMT as a promoter of neuroplasticity. This review summarizes current knowledge on these activities, potential therapeutic benefits of these compounds and their limitations as candidates for neuroprotective therapies. We envision that treatments with QCT, CBD, and DMT could be effective either when combined or when targeting different stages of these diseases.