Phytochemicals as future drugs for Parkinson’s disease: a comprehensive review

Abstract Parkinson’s disease (PD) is the second most common chronic neurodegenerative disease that affects motor skills and cognitive performance. The conventional therapeutic approaches for the management of PD are just able to alleviate symptoms. Exploring for achieving novel substances with therapeutic benefits in PD patients is the focus of a wide range of current investigations. The aim of the present study is to comprehensively review phytochemicals with protective or therapeutic activities in PD and focus on their neuropsychopharmacological mechanisms. Various subgroups of polyphenols (flavonoids, phenolic acids, stilbenes, and lignanes) and terpenes are the most abundant groups of phytochemicals with well-established antiparkinsonian effects. Other phytochemical categories, such as alkaloids, cinnamates, carbohydrates, amino acids, and fatty acid amides, also have some representatives with positive effects in PD. Phytochemicals perform their antiparkinsonian effect through several mechanisms of action, including suppressing apoptosis (via the reduction of Bax/Bcl-2, caspase-3, -8, and -9, and α-synuclein accumulation), decreasing dopaminergic neuronal loss and dopamine depletion, reducing the expression of proinflammatory cytokines (such as prostaglandin E 2 , interleukin-6, interleukin-1β, and nuclear factor-κB), and modulating nuclear and cellular inflammatory signaling, elevation of neurotrophic factors, and improvement of antioxidant status. Plant-derived natural products can be considered as future pharmaceutical drugs or adjuvant treatment with conventional therapeutic approaches to improve their efficacy and alleviate their psychological adverse effects in the management of PD. Well-designed clinical trials are mandatory to evaluate the protective and healing benefits of phytochemicals as promising future drugs in the management of neurodegenerative diseases.