Neurodegenerative diseases (NDs) constitute a large group of pathological conditions,
characterized by a progressive loss of neuronal cells, which compromise motor and/or
cognitive functions. The most common NDs are Alzheimer's disease (AD), amyotrophic
lateral sclerosis (ALS), Parkinson's disease (PD), and Huntington's disease (HD).
The causes of these pathologies are multifactorial and not fully understood, but it
is well known that factors related to aging and to the overproduction of free radical
and reactive oxygen species lead to oxidative stress and to cell death, which are
extremely related. Whereas oxidative stress plays an unquestionable and central role
in NDs, the control of free radicals and reactive oxygen species levels represents
an interesting and promising strategy to delay neurodegeneration and attenuate the
associated symptoms.
In this context, several natural bioactive compounds isolated from plants, fungi,
and algae, among others, and also synthetic compounds inspired by natural scaffolds,
which present antioxidant properties, including vitamins C and E, anthocyanins, and
phenolic compounds, are extensively described as potential palliative agents of neurodegenerative
symptoms. In vitro and in vivo studies, performed with extracts and fractions of plants
and with isolated natural bioactive compounds, provide evidence of the role of these
substances in the modulation of the cellular redox balance and in the reduction of
the formation of reactive oxygen species originating from oxidative stress, thereby
demonstrating their great value as antioxidant agents and cellular protectors.
In this special issue, articles were selected that address new therapeutic alternatives
on the antioxidant and anti-inflammatory role and the consequent neuroprotetor of
natural (or inspired) bioactive compounds in the prevention/treatment or improvement
of neurodegenerative diseases. This special issue compiles fifteen (15) manuscripts
including three (3) reviews and twelve (12) research papers, which show recent research
about the discovery of plant-derived antioxidants with application in neurodegenerative
diseases.
The review by R. Avila-Sosa et al. describes the antioxidant effects of main bioactive
components isolated from Amazonian fruits. Among other activities, the authors highlight
antioxidants, immunomodulatory, anticancer, anti-inflammatory, and antidepressant
properties of phenolic compounds, unsaturated fatty acids, carotenoids, phytosterols,
and tocopherols.
The review by X. Zhao et al. highlights the benefits of vitamin supplementation in
the treatment or improvement of the clinical symptoms of Parkinson's disease. The
authors summarized the biological correlations between vitamins and PD as well as
the underlying pathophysiological mechanisms, demonstrating that the antioxidant properties
and the regulatory gene expression promoted by vitamins are beneficial for the treatment/prevention
of PD.
Due to the fact that many diseases that affect the central nervous system also promote
blood-brain barrier (BBB) destruction, consequently increasing BBB permeability, in
the third review, Z. Chen et al. carry out a systematic review of about the evidence
of possible neuroprotective borneol (terpenoid) effects for ischemic stroke. The authors
have found much evidence that borneol exerted a significant decrease of BBB permeability,
thus acting as a neuroprotector.
Ten of the eleven research articles deal with the proof of antioxidant, anti-inflammatory,
and neuroprotective activities in in vitro and/or in vivo models, of plant and/or
cyanobacteria extracts, and natural products isolated or chemically modified. The
only article that eludes this theme is the work of A. F. M. Monteiro et al. which
carried out in silico studies aimed at the identification of potentially useful flavonoids
for in vitro/in vivo screening in Parkinson and Alzheimer models.
G. Oboh et al.'s group found that the alkaloid extract from the African Jointfir (Gnetum
africanum) is capable to counteract the Mn-induced elevation in AChE activity, NO,
and ROS levels. I. K. Martins et al. observed the neuroprotective effect of the methanolic
fraction of Anacardium microcarpum (from Brazil). This fraction was able to prevent
neurodegeneration through the chelating properties toward ROS species, which is dependent
on ERK1/2 and AKT phosphorylation; however, it does not prevent mitochondrial damage
by 6-OHDA.
K. Adamczyk et al. evaluated the antihyaluronidase, antiacetylcholinestarase, and
anti-DPPH activities of several Eleutherococcus species cultivated in Poland. The
methanolic extract was shown to be rich in polyphenols and promoted a reduction in
DPPH in a time-dependent mode. E. gracilistylus and E. sessiliflorus showed the highest
inhibition of AChE, and E. henryi was the best hyaluronidase inhibitor. R. B. de Oliveira
Caland et al. observed the neuroprotective and antioxidative effect of pasteurized
orange juice (Citrus sinensis L.) rich in carotenoids. The authors observed reduction
in ROS production and upregulation of the expression of antioxidant and chaperonin
genes, generating greater resistance to oxidative stress.
I.-C. Chen et al. evaluated the neuroprotective effects of formulated Chinese herbal
medicines in a cell model of tauopathy. Shaoyao Gancao Tang (P. lactiflora and G.
uralensis in a 1 : 1 ratio) presented the best antioxidative and anti-inflammatory
results, reducing the tau misfolding and the production of the reactive oxygen species
(ROS) level, especially nitric oxide (NO). In the research article by D. Nuzzo et
al.'s group, the authors observed the neuroprotective effect of the cyanobacteria
extract (Klamin®). Klamin® interferes with Aβ aggregation kinetics, exerts a protective
role against beta amyloid (Aβ), and promotes activation of IL-6 and IL-1β inflammatory
cytokines.
Y.-J. Wang et al. observed the antioxidant and neuroprotective activities of the extract
of Centipeda minima and four isolated sesquiterpenoids. They found that the extract
reduces glutamate and tert-butyl hydroperoxide-induced neuronal death, ROS production,
and mitochondria dysfunction. Among the isolated sesquiterpenoids, 6-O-Angeloylplenolin
and arnicolide D were the most active and responsible for the activation of the Nrf2
pathway and inhibition of ROS production. The study conducted by K. K. S. Narasimhan
et al. has demonstrated that scopoletin (one of the main components from Morinda citrifolia)
prevents oxidative injury and mitigates protein aggregation by the markedly upregulated
DJ-1/Nrf2/ARE pathway.
L. Subedi et al. observed the antioxidant and anti-inflammatory effects of sulforaphane-enriched
broccoli sprouts (SEBS) which lead to their neuroprotective effects. SEBS has protective
effects of neuroinflammatory conditions by inhibition of the LPS-induced activation
of the NF-κB signaling pathway, by the secretion of inflammatory proteins (inhibition
of inflammatory cascade), and least by the upregulation of the expression of Nrf2
and HO-1, improving the scopolamine-induced memory impairment in mice. Y. Lee et al.
verified that γ-mangostin (one of the major constituents from Garcinia mangostana
fruits) reduces the oxidative neurotoxicity through the inhibition of H2O2-induced
DNA fragmentation, ROS generation, lipid peroxidation, and DPPH radical formation,
which is associated with the protection against H2O2-induced oxidative neuronal death.
Orally, in vivo, γ-mangostin also improved scopolamine-induced memory impairment in
mice. And finally, J.-S. Ye et al. observe the neuroprotective effect of Honokiol
(a lignan isolated from the Magnolia genus) in postoperative cognitive change. Honokiol-mediated
mitophagy inhibits the activation of the NLRP3 inflammasome and neuroinflammation
in the hippocampus by increasing the expression of LC3-II, Beclin-1, Parkin, and PINK-1
at protein levels and through attenuation of mitochondrial structure damage and reduction
of mtROS and MDA generation.
This compilation of articles gives us an up-to-date sample of the therapeutic potential
of natural products in providing potential drugs and/or plant candidates to treat,
prevent, or ameliorate the oxidative stress associated with neurodegenerative diseases
including, but not limited to, Parkinson's and Alzheimer's diseases. We are sure that
the information available in this issue will be very useful and will contribute to
the future success of new therapies for neurodegenerative diseases.