Abstract
Parkinson's disease (PD) is the second-most common neurodegenerative chronic disease affecting both cognitive performance and motor functions in aged people. Yet despite the prevalence of this disease, the current therapeutic options for the management of PD can only alleviate motor symptoms. Research has explored novel substances for naturally derived antioxidant phytochemicals with potential therapeutic benefits for PD patients through their neuroprotective mechanism, targeting oxidative stress, neuroinflammation, abnormal protein accumulation, mitochondrial dysfunction, endoplasmic reticulum stress, neurotrophic factor deficit, and apoptosis. The aim of the present study is to perform a comprehensive evaluation of naturally derived antioxidant phytochemicals with neuroprotective or therapeutic activities in PD, focusing on their neuropharmacological mechanisms, including modulation of antioxidant and anti-inflammatory activity, growth factor induction, neurotransmitter activity, direct regulation of mitochondrial apoptotic machinery, prevention of protein aggregation via modulation of protein folding, modification of cell signaling pathways, enhanced systemic immunity, autophagy, and proteasome activity. In addition, we provide data showing the relationship between nuclear factor E2-related factor 2 (Nrf2) and PD is supported by studies demonstrating that antiparkinsonian phytochemicals can activate the Nrf2/antioxidant response element (ARE) signaling pathway and Nrf2-dependent protein expression, preventing cellular oxidative damage and PD. Furthermore, we explore several experimental models that evaluated the potential neuroprotective efficacy of antioxidant phytochemical derivatives for their inhibitory effects on oxidative stress and neuroinflammation in the brain. Finally, we highlight recent developments in the nanodelivery of antioxidant phytochemicals and its neuroprotective application against pathological conditions associated with oxidative stress. In conclusion, naturally derived antioxidant phytochemicals can be considered as future pharmaceutical drug candidates to potentially alleviate symptoms or slow the progression of PD. However, further well-designed clinical studies are required to evaluate the protective and therapeutic benefits of phytochemicals as promising drugs in the management of PD.
Highlights
Parkinson’s disease (PD) is a common progressive chronic neurodegenerative movement disorder that increases with age
Sulforaphane, a natural phytochemical, significantly attenuated cell damage and reversed the reduction of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P) H:quinone oxidoreductase-1 (NQO1) expression induced by MPP+ neurotoxicity; these protective effects are due in part to the activation of the Nrf2-antioxidant response element (ARE) signaling pathway [112]
Authors found that pinostrobin promoted phosphorylation of PI3K/AKT and extracellular signal-regulated kinase (ERK), and pharmacological inhibition of PI3K/AKT or ERK signaling diminished pinostrobin-induced Nrf2/ARE activation and neuroprotective actions against MPTP/MPP+induced neurotoxicity in PD models [114]. These findings strongly indicate that treatment of PD via activation of the Nrf2-ARE signaling pathway may be possible
Summary
Parkinson’s disease (PD) is a common progressive chronic neurodegenerative movement disorder that increases with age. The therapeutic and beneficial effects of these phytochemicals provide nutrition for normal living cells, fight disease-causing agents, strengthen the immune system, and act as antioxidants [20] Plant products and their bioactive phytochemicals can efficiently scavenge oxygen free radicals and boost the cellular antioxidant defense system and related molecules, thereby protecting cells from oxidative damage [20, 21]. Various preclinical reports have described a number of natural pharmacological candidates that can coactivate the antioxidant defense system and neurotrophic factor-mediated cell survival systems [26,27,28,29,30,31], suggesting that these phytochemicals have therapeutic potential for the treatment of oxidative stress-mediated NDDs, especially PD. We highlight some potentially neuroprotective active derivatives of antioxidant phytochemicals and phytochemicalbased nanodelivery systems that fight pathological conditions associated with aging-related oxidative stress.
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