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Neuroprotective Potential of Bioactive Natural Compounds in Oxidative Stress Conditions II

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 25620

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Guest Editor
Ruder Boskovic Institute, Zagreb, Croatia
Interests: model membranes; biodegradable nanomaterials; lipid peroxidation; natural products; antioxidants
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Oxidative stress is one of the major causes of neuronal death in a variety of neurodegenerative diseases. Its contribution to neuropsychiatric disorders has been suggested as well. As the world’s population is getting older, neurodegenerative diseases, such as Alzheimer´s and Parkinson´s disease, represent a growing medical, economic, and social issue. Although considerable progress has been made towards understanding the pathological mechanisms that underlie development and progression of these diseases at the molecular and cellular levels, this knowledge has not yet been successfully translated into the clinics.

Oxidative stress occurs when increased accumulation of reactive oxygen species (ROS) overwhelms the brain’s intrinsic capacity of oxidative defence, leading to detrimental effects on neuronal functioning and viability. Many pieces of evidence indicate that deregulation of metal homeostasis, accompanied with enhanced production of free radicals and increased oxidative stress, could be directly involved in the onset and progression of neurodegenerative diseases. On the other hand, natural products have potential to re-establish redox homeostasis and reduce or prevent metal-induced oxidative damage. They may act as antioxidants, metal chelators and modulators of intracellular signalling. Hence, bioactive natural molecules represent a promising multi-target drug option, particularly at the early stages of neurodegenerative processes.

Therefore, this Special Issue of Molecules is dedicated to research and review articles that cover the latest findings about the beneficial effects of bioactive natural compounds in the prevention and therapy of oxidative stress-driven neuronal injury. Studies devoted to investigation of efficacy and mechanisms of action of various bioactive molecules with the potential to regain metal homeostasis in the treatment of neurodegenerative diseases are particularly welcome.

Dr. Maja Jazvinšćak Jembrek
Dr. Suzana Šegota
Guest Editors

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Keywords

  • Oxidative stress
  • Natural antioxidants
  • Neuroprotection
  • Metal homeostasis

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Published Papers (8 papers)

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Research

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31 pages, 5575 KiB  
Article
Bacopa Protects against Neurotoxicity Induced by MPP+ and Methamphetamine
by Michela Ferrucci, Carla Letizia Busceti, Gloria Lazzeri, Francesca Biagioni, Stefano Puglisi-Allegra, Alessandro Frati, Paola Lenzi and Francesco Fornai
Molecules 2022, 27(16), 5204; https://doi.org/10.3390/molecules27165204 - 15 Aug 2022
Cited by 1 | Viewed by 1421
Abstract
The neurotoxins methamphetamine (METH) and 1-methyl-4-phenylpyridinium (MPP+) damage catecholamine neurons. Although sharing the same mechanism to enter within these neurons, METH neurotoxicity mostly depends on oxidative species, while MPP+ toxicity depends on the inhibition of mitochondrial activity. This explains why [...] Read more.
The neurotoxins methamphetamine (METH) and 1-methyl-4-phenylpyridinium (MPP+) damage catecholamine neurons. Although sharing the same mechanism to enter within these neurons, METH neurotoxicity mostly depends on oxidative species, while MPP+ toxicity depends on the inhibition of mitochondrial activity. This explains why only a few compounds protect against both neurotoxins. Identifying a final common pathway that is shared by these neurotoxins is key to prompting novel remedies for spontaneous neurodegeneration. In the present study we assessed whether natural extracts from Bacopa monnieri (BM) may provide a dual protection against METH- and MPP+-induced cell damage as measured by light and electron microscopy. The protection induced by BM against catecholamine cell death and degeneration was dose-dependently related to the suppression of reactive oxygen species (ROS) formation and mitochondrial alterations. These were measured by light and electron microscopy with MitoTracker Red and Green as well as by the ultrastructural morphometry of specific mitochondrial structures. In fact, BM suppresses the damage of mitochondrial crests and matrix dilution and increases the amount of healthy and total mitochondria. The present data provide evidence for a natural compound, which protects catecholamine cells independently by the type of experimental toxicity. This may be useful to counteract spontaneous degenerations of catecholamine cells. Full article
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12 pages, 7675 KiB  
Article
Nobiletin Alleviates Astrocyte Activation and Oxidative Stress Induced by Hypoxia In Vitro
by Dandan Wang, Fengjuan Gao, Fangyuan Hu and Jihong Wu
Molecules 2022, 27(6), 1962; https://doi.org/10.3390/molecules27061962 - 17 Mar 2022
Cited by 10 | Viewed by 2127
Abstract
Increasing evidence indicates that nobiletin (NOB) is a promising neuroprotective agent. Astrocyte activation plays a key role in neurodegenerative disorders. Thus, this study aims to investigate the effects of NOB on astrocyte activation and the potential mechanisms. In this study, astrocytes were exposed [...] Read more.
Increasing evidence indicates that nobiletin (NOB) is a promising neuroprotective agent. Astrocyte activation plays a key role in neurodegenerative disorders. Thus, this study aims to investigate the effects of NOB on astrocyte activation and the potential mechanisms. In this study, astrocytes were exposed to hypoxia injury for 24 h to induce activation in vitro. Glial fibrillary acidic protein (GFAP) was chosen as a marker of astrocyte activation. To evaluate the effects of NOB on the migration of activated astrocytes, we used a scratch wound healing assay and Transwell migration assay. In addition, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), mitochondrial membrane potential, Nrf2 and HO-1 were measured to investigate the mechanisms of NOB in the activation of astrocytes. We found that NOB alleviated astrocyte activation and decreased GFAP expression during hypoxia. Simultaneously, NOB alleviated the migration of astrocytes induced by hypoxia. With NOB treatment, hypoxia-induced oxidative stress was partially reversed, including reducing the production of ROS and MDA. Furthermore, NOB significantly improved the mitochondrial dysfunction in activated astrocytes. Finally, NOB promoted Nrf2 nuclear translocation and HO-1 expression in response to continuous oxidative damage. Our study indicates, for the first time, that NOB alleviates the activation of astrocytes induced by hypoxia in vitro, in part by ameliorating oxidative stress and mitochondrial dysfunction. This provides new insights into the neuroprotective effects of NOB. Full article
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13 pages, 1458 KiB  
Article
Reduction of Deuterium Level Supports Resistance of Neurons to Glucose Deprivation and Hypoxia: Study in Cultures of Neurons and on Animals
by Alexandr Kravtsov, Stanislav Kozin, Alexandr Basov, Elena Butina, Mikhail Baryshev, Vadim Malyshko, Arkady Moiseev, Anna Elkina and Stepan Dzhimak
Molecules 2022, 27(1), 243; https://doi.org/10.3390/molecules27010243 - 31 Dec 2021
Cited by 14 | Viewed by 2024
Abstract
The effect of a reduced deuterium (D) content in the incubation medium on the survival of cultured neurons in vitro and under glucose deprivation was studied. In addition, we studied the effect of a decrease in the deuterium content in the rat brain [...] Read more.
The effect of a reduced deuterium (D) content in the incubation medium on the survival of cultured neurons in vitro and under glucose deprivation was studied. In addition, we studied the effect of a decrease in the deuterium content in the rat brain on oxidative processes in the nervous tissue, its antioxidant protection, and training of rats in the T-shaped maze test under hypoxic conditions. For experiments with cultures of neurons, 7–8-day cultures of cerebellar neurons were used. Determination of the rate of neuronal death in cultures was carried out using propidium iodide. Acute hypoxia with hypercapnia was simulated in rats by placing them in sealed vessels with a capacity of 1 L. The effect on oxidative processes in brain tissues was assessed by changes in the level of free radical oxidation and malondialdehyde. The effect on the antioxidant system of the brain was assessed by the activity of catalase. The study in the T-maze was carried out in accordance with the generally accepted methodology, the skill of alternating right-sided and left-sided loops on positive reinforcement was developed. This work has shown that a decrease in the deuterium content in the incubation medium to a level of −357‰ has a neuroprotective effect, increasing the survival rate of cultured neurons under glucose deprivation. When exposed to hypoxia, a preliminary decrease in the deuterium content in the rat brain to −261‰ prevents the development of oxidative stress in their nervous tissue and preserves the learning ability of animals in the T-shaped maze test at the level of the control group. A similar protective effect during the modification of the 2H/1H internal environment of the body by the consumption of DDW can potentially be used for the prevention of pathological conditions associated with the development of oxidative stress with damage to the central nervous system. Full article
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14 pages, 2177 KiB  
Article
Neuroprotective Effect of Quercetin during Cerebral Ischemic Injury Involves Regulation of Essential Elements, Transition Metals, Cu/Zn Ratio, and Antioxidant Activity
by Ming-Cheng Lin, Chien-Chi Liu, Chin-Sheng Liao and Ju-Hai Ro
Molecules 2021, 26(20), 6128; https://doi.org/10.3390/molecules26206128 - 11 Oct 2021
Cited by 8 | Viewed by 1848
Abstract
Cerebral ischemia results in increased oxidative stress in the affected brain. Accumulating evidence suggests that quercetin possesses anti-oxidant and anti-inflammatory properties. The essential elements magnesium (Mg), zinc (Zn), selenium (Se), and transition metal iron (Fe), copper (Cu), and antioxidants superoxide dismutase (SOD) and [...] Read more.
Cerebral ischemia results in increased oxidative stress in the affected brain. Accumulating evidence suggests that quercetin possesses anti-oxidant and anti-inflammatory properties. The essential elements magnesium (Mg), zinc (Zn), selenium (Se), and transition metal iron (Fe), copper (Cu), and antioxidants superoxide dismutase (SOD) and catalase (CAT) are required for brain functions. This study investigates whether the neuroprotective effects of quercetin on the ipsilateral brain cortex involve altered levels of essential trace metals, the Cu/Zn ratio, and antioxidant activity. Rats were intraperitoneally administered quercetin (20 mg/kg) once daily for 10 days before ischemic surgery. Cerebral ischemia was induced by ligation of the right middle cerebral artery and the right common carotid artery for 1 h. The ipsilateral brain cortex was homogenized and the supernatant was collected for biochemical analysis. Results show that rats pretreated with quercetin before ischemia significantly increased Mg, Zn, Se, SOD, and CAT levels, while the malondialdehyde, Fe, Cu, and the Cu/Zn ratio clearly decreased as compared to the untreated ligation subject. Taken together, our findings suggest that the mechanisms underlying the neuroprotective effects of quercetin during cerebral ischemic injury involve the modulation of essential elements, transition metals, Cu/Zn ratio, and antioxidant activity. Full article
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17 pages, 2765 KiB  
Article
Noscapine Prevents Rotenone-Induced Neurotoxicity: Involvement of Oxidative Stress, Neuroinflammation and Autophagy Pathways
by Richard L. Jayaraj, Rami Beiram, Sheikh Azimullah, Nagoor Meeran M. F., Shreesh K. Ojha, Abdu Adem and Fakhreya Yousuf Jalal
Molecules 2021, 26(15), 4627; https://doi.org/10.3390/molecules26154627 - 30 Jul 2021
Cited by 9 | Viewed by 3182
Abstract
Parkinson’s disease is characterized by the loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) and the resultant loss of dopamine in the striatum. Various studies have shown that oxidative stress and neuroinflammation plays a major role in PD progression. In addition, [...] Read more.
Parkinson’s disease is characterized by the loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) and the resultant loss of dopamine in the striatum. Various studies have shown that oxidative stress and neuroinflammation plays a major role in PD progression. In addition, the autophagy lysosome pathway (ALP) plays an important role in the degradation of aggregated proteins, abnormal cytoplasmic organelles and proteins for intracellular homeostasis. Dysfunction of ALP results in the accumulation of α-synuclein and the loss of dopaminergic neurons in PD. Thus, modulating ALP is becoming an appealing therapeutic intervention. In our current study, we wanted to evaluate the neuroprotective potency of noscapine in a rotenone-induced PD rat model. Rats were administered rotenone injections (2.5 mg/kg, i.p.,) daily followed by noscapine (10 mg/kg, i.p.,) for four weeks. Noscapine, an iso-qinulinin alkaloid found naturally in the Papaveraceae family, has traditionally been used in the treatment of cancer, stroke and fibrosis. However, the neuroprotective potency of noscapine has not been analyzed. Our study showed that administration of noscapine decreased the upregulation of pro-inflammatory factors, oxidative stress, and α-synuclein expression with a significant increase in antioxidant enzymes. In addition, noscapine prevented rotenone-induced activation of microglia and astrocytes. These neuroprotective mechanisms resulted in a decrease in dopaminergic neuron loss in SNpc and neuronal fibers in the striatum. Further, noscapine administration enhanced the mTOR-mediated p70S6K pathway as well as inhibited apoptosis. In addition to these mechanisms, noscapine prevented a rotenone-mediated increase in lysosomal degradation, resulting in a decrease in α-synuclein aggregation. However, further studies are needed to further develop noscapine as a potential therapeutic candidate for PD treatment. Full article
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Review

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21 pages, 2981 KiB  
Review
The Signaling Pathways and Targets of Natural Compounds from Traditional Chinese Medicine in Treating Ischemic Stroke
by Xing-Hua Li, Feng-Ting Yin, Xiao-Hang Zhou, Ai-Hua Zhang, Hui Sun, Guang-Li Yan and Xi-Jun Wang
Molecules 2022, 27(10), 3099; https://doi.org/10.3390/molecules27103099 - 12 May 2022
Cited by 20 | Viewed by 4284
Abstract
Ischemic stroke (IS) is a common neurological disorder associated with high disability rates and mortality rates. At present, recombinant tissue plasminogen activator (r-tPA) is the only US(FDA)-approved drug for IS. However, due to the narrow therapeutic window and risk of intracerebral hemorrhage, r-tPA [...] Read more.
Ischemic stroke (IS) is a common neurological disorder associated with high disability rates and mortality rates. At present, recombinant tissue plasminogen activator (r-tPA) is the only US(FDA)-approved drug for IS. However, due to the narrow therapeutic window and risk of intracerebral hemorrhage, r-tPA is currently used in less than 5% of stroke patients. Natural compounds have been widely used in the treatment of IS in China and have a wide range of therapeutic effects on IS by regulating multiple targets and signaling pathways. The keywords “ischemia stroke, traditional Chinese Medicine, Chinese herbal medicine, natural compounds” were used to search the relevant literature in PubMed and other databases over the past five years. The results showed that JAK/STAT, NF-κB, MAPK, Notch, Nrf2, and PI3K/Akt are the key pathways, and SIRT1, MMP9, TLR4, HIF-α are the key targets for the natural compounds from traditional Chinese medicine in treating IS. This study aims to update and summarize the signaling pathways and targets of natural compounds in the treatment of IS, and provide a base of information for the future development of effective treatments for IS. Full article
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20 pages, 1336 KiB  
Review
Neuroprotective Potential of Chrysin: Mechanistic Insights and Therapeutic Potential for Neurological Disorders
by Awanish Mishra, Pragya Shakti Mishra, Ritam Bandopadhyay, Navneet Khurana, Efthalia Angelopoulou, Yam Nath Paudel and Christina Piperi
Molecules 2021, 26(21), 6456; https://doi.org/10.3390/molecules26216456 - 26 Oct 2021
Cited by 29 | Viewed by 4906
Abstract
Chrysin, a herbal bioactive molecule, exerts a plethora of pharmacological effects, including anti-oxidant, anti-inflammatory, neuroprotective, and anti-cancer. A growing body of evidence has highlighted the emerging role of chrysin in a variety of neurological disorders, including Alzheimer’s and Parkinson’s disease, epilepsy, multiple sclerosis, [...] Read more.
Chrysin, a herbal bioactive molecule, exerts a plethora of pharmacological effects, including anti-oxidant, anti-inflammatory, neuroprotective, and anti-cancer. A growing body of evidence has highlighted the emerging role of chrysin in a variety of neurological disorders, including Alzheimer’s and Parkinson’s disease, epilepsy, multiple sclerosis, ischemic stroke, traumatic brain injury, and brain tumors. Based on the results of recent pre-clinical studies and evidence from studies in humans, this review is focused on the molecular mechanisms underlying the neuroprotective effects of chrysin in different neurological diseases. In addition, the potential challenges, and opportunities of chrysin’s inclusion in the neurotherapeutics repertoire are critically discussed. Full article
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20 pages, 2152 KiB  
Review
The Neuroprotective Effect of Tea Polyphenols on the Regulation of Intestinal Flora
by Zhicheng Zhang, Yuting Zhang, Junmin Li, Chengxin Fu and Xin Zhang
Molecules 2021, 26(12), 3692; https://doi.org/10.3390/molecules26123692 - 17 Jun 2021
Cited by 28 | Viewed by 4603
Abstract
Tea polyphenols (TPs) are the general compounds of natural polyhydroxyphenols extracted in tea. Although a large number of studies have shown that TPs have obvious neuroprotective and neuro repair effects, they are limited due to the low bioavailability in vivo. However, TPs can [...] Read more.
Tea polyphenols (TPs) are the general compounds of natural polyhydroxyphenols extracted in tea. Although a large number of studies have shown that TPs have obvious neuroprotective and neuro repair effects, they are limited due to the low bioavailability in vivo. However, TPs can act indirectly on the central nervous system by affecting the “microflora–gut–brain axis”, in which the microbiota and its composition represent a factor that determines brain health. Bidirectional communication between the intestinal microflora and the brain (microbe–gut–brain axis) occurs through a variety of pathways, including the vagus nerve, immune system, neuroendocrine pathways, and bacteria-derived metabolites. This axis has been shown to influence neurotransmission and behavior, which is usually associated with neuropsychiatric disorders. In this review, we discuss that TPs and their metabolites may provide benefits by restoring the imbalance of intestinal microbiota and that TPs are metabolized by intestinal flora, to provide a new idea for TPs to play a neuroprotective role by regulating intestinal flora. Full article
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