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Neuroprotective Potential of Bioactive Natural Compounds in Oxidative Stress Conditions III

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

Deadline for manuscript submissions: 30 April 2024 | Viewed by 7533

Special Issue Editors

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 the 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 defense, 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 the 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 signaling. 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 the investigation of the 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 (4 papers)

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Research

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24 pages, 11744 KiB  
Article
Ethanolic Extract of Polygonum minus Protects Differentiated Human Neuroblastoma Cells (SH-SY5Y) against H2O2-Induced Oxidative Stress
Molecules 2023, 28(18), 6726; https://doi.org/10.3390/molecules28186726 - 20 Sep 2023
Viewed by 1109
Abstract
Neuronal models are an important tool in neuroscientific research. Hydrogen peroxide (H2O2), a major risk factor of neuronal oxidative stress, initiates a cascade of neuronal cell death. Polygonum minus Huds, known as ‘kesum’, is widely used in traditional medicine. [...] Read more.
Neuronal models are an important tool in neuroscientific research. Hydrogen peroxide (H2O2), a major risk factor of neuronal oxidative stress, initiates a cascade of neuronal cell death. Polygonum minus Huds, known as ‘kesum’, is widely used in traditional medicine. P. minus has been reported to exhibit a few medicinal and pharmacological properties. The current study aimed to investigate the neuroprotective effects of P. minus ethanolic extract (PMEE) on H2O2-induced neurotoxicity in SH-SY5Y cells. LC–MS/MS revealed the presence of 28 metabolites in PMEE. Our study showed that the PMEE provided neuroprotection against H2O2-induced oxidative stress by activating the Nrf2/ARE, NF-κB/IκB and MAPK signaling pathways in PMEE pre-treated differentiated SH-SY5Y cells. Meanwhile, the acetylcholine (ACH) level was increased in the oxidative stress-induced treatment group after 4 h of exposure with H2O2. Molecular docking results with acetylcholinesterase (AChE) depicted that quercitrin showed the highest docking score at −9.5 kcal/mol followed by aloe-emodin, afzelin, and citreorosein at −9.4, −9.3 and −9.0 kcal/mol, respectively, compared to the other PMEE’s identified compounds, which show lower docking scores. The results indicate that PMEE has neuroprotective effects on SH-SY5Y neuroblastoma cells in vitro. In conclusion, PMEE may aid in reducing oxidative stress as a preventative therapy for neurodegenerative diseases. Full article
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20 pages, 11902 KiB  
Article
The Potential Neuroprotective Effect of Thymoquinone on Scopolamine-Induced In Vivo Alzheimer’s Disease-like Condition: Mechanistic Insights
Molecules 2023, 28(18), 6566; https://doi.org/10.3390/molecules28186566 - 11 Sep 2023
Cited by 1 | Viewed by 1228
Abstract
Background: Alzheimer’s disease (AD) is a common neurodegenerative disorder without effective treatment. Thymoquinone (TQ) has demonstrated potential in exhibiting anti-inflammatory, anti-cancer, and antioxidant characteristics. Despite TQ’s neuroprotection effect, there is a scarcity of information regarding its application in AD research, and its molecular [...] Read more.
Background: Alzheimer’s disease (AD) is a common neurodegenerative disorder without effective treatment. Thymoquinone (TQ) has demonstrated potential in exhibiting anti-inflammatory, anti-cancer, and antioxidant characteristics. Despite TQ’s neuroprotection effect, there is a scarcity of information regarding its application in AD research, and its molecular trajectories remain ambiguous. Thus, the objective of the current investigation was to examine the potential beneficial effects and underlying mechanisms of TQ in scopolamine (SCOP)-induced neuronal injury to mimic AD in vivo model. Methods: Thirty mice were divided into normal, SCOP, and TQ groups. The Y-maze and pole climbing tests were performed to measure memory and motor performance. Afterwards, histopathological and immunohistochemical examinations were carried out. Furthermore, peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling pathway-related proteins and genes were detected with an emphasis on the role of miR-9. Results: TQ has the potential to ameliorate cognitive deficits observed in SCOP-induced AD-like model, as evidenced by the improvement in behavioral outcomes, histopathological changes, modulation of the expression pattern of PPAR-γ downstream targets with a significant decrease in the deposition of amyloid beta (Aβ). Conclusions: TQ provided meaningful multilevel neuroprotection through its anti-inflammatory and its PPAR-γ agonist activity. Consequently, TQ may possess a potential beneficial role against AD development. Full article
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20 pages, 13268 KiB  
Article
Marine Fish-Derived Lysophosphatidylcholine: Properties, Extraction, Quantification, and Brain Health Application
Molecules 2023, 28(7), 3088; https://doi.org/10.3390/molecules28073088 - 30 Mar 2023
Cited by 3 | Viewed by 2805
Abstract
Long-chain omega-3 fatty acids esterified in lysophosphatidylcholine (LPC-omega-3) are the most bioavailable omega-3 fatty acid form and are considered important for brain health. Lysophosphatidylcholine is a hydrolyzed phospholipid that is generated from the action of either phospholipase PLA1 or PLA2. [...] Read more.
Long-chain omega-3 fatty acids esterified in lysophosphatidylcholine (LPC-omega-3) are the most bioavailable omega-3 fatty acid form and are considered important for brain health. Lysophosphatidylcholine is a hydrolyzed phospholipid that is generated from the action of either phospholipase PLA1 or PLA2. There are two types of LPC; 1-LPC (where the omega-3 fatty acid at the sn-2 position is acylated) and 2-LPC (where the omega-3 fatty acid at the sn-1 position is acylated). The 2-LPC type is more highly bioavailable to the brain than the 1-LPC type. Given the biological and health aspects of LPC types, it is important to understand the structure, properties, extraction, quantification, functional role, and effect of the processing of LPC. This review examines various aspects involved in the extraction, characterization, and quantification of LPC. Further, the effects of processing methods on LPC and the potential biological roles of LPC in health and wellbeing are discussed. DHA-rich-LysoPLs, including LPC, can be enzymatically produced using lipases and phospholipases from wide microbial strains, and the highest yields were obtained by Lipozyme RM-IM®, Lipozyme TL-IM®, and Novozym 435®. Terrestrial-based phospholipids generally contain lower levels of long-chain omega-3 PUFAs, and therefore, they are considered less effective in providing the same health benefits as marine-based LPC. Processing (e.g., thermal, fermentation, and freezing) reduces the PL in fish. LPC containing omega-3 PUFA, mainly DHA (C22:6 omega-3) and eicosapentaenoic acid EPA (C20:5 omega-3) play important role in brain development and neuronal cell growth. Additionally, they have been implicated in supporting treatment programs for depression and Alzheimer’s. These activities appear to be facilitated by the acute function of a major facilitator superfamily domain-containing protein 2 (Mfsd2a), expressed in BBB endothelium, as a chief transporter for LPC-DHA uptake to the brain. LPC-based delivery systems also provide the opportunity to improve the properties of some bioactive compounds during storage and absorption. Overall, LPCs have great potential for improving brain health, but their safety and potentially negative effects should also be taken into consideration. Full article
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Review

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28 pages, 3148 KiB  
Review
Emerging Role of Plant-Based Bioactive Compounds as Therapeutics in Parkinson’s Disease
Molecules 2023, 28(22), 7588; https://doi.org/10.3390/molecules28227588 - 14 Nov 2023
Viewed by 1536
Abstract
Neurological ailments, including stroke, Alzheimer’s disease (AD), epilepsy, Parkinson’s disease (PD), and other related diseases, have affected around 1 billion people globally to date. PD stands second among the common neurodegenerative diseases caused as a result of dopaminergic neuron loss in the midbrain’s [...] Read more.
Neurological ailments, including stroke, Alzheimer’s disease (AD), epilepsy, Parkinson’s disease (PD), and other related diseases, have affected around 1 billion people globally to date. PD stands second among the common neurodegenerative diseases caused as a result of dopaminergic neuron loss in the midbrain’s substantia nigra regions. It affects cognitive and motor activities, resulting in tremors during rest, slow movement, and muscle stiffness. There are various traditional approaches for the management of PD, but they provide only symptomatic relief. Thus, a survey for finding new biomolecules or substances exhibiting the therapeutic potential to patients with PD is the main focus of present-day research. Medicinal plants, herbal formulations, and natural bioactive molecules have been gaining much more attention in recent years as synthetic molecules orchestrate a number of undesired effects. Several in vitro, in vivo, and in silico studies in the recent past have demonstrated the therapeutic potential of medicinal plants, herbal formulations, and plant-based bioactives. Among the plant-based bioactives, polyphenols, terpenes, and alkaloids are of particular interest due to their potent anti-inflammatory, antioxidant, and brain-health-promoting properties. Further, there are no concise, elaborated articles comprising updated mechanism-of-action-based reviews of the published literature on potent, recently investigated (2019–2023) medicinal plants, herbal formulations, and plant based-bioactive molecules, including polyphenols, terpenes, and alkaloids, as a method for the management of PD. Therefore, we designed the current review to provide an illustration of the efficacious role of various medicinal plants, herbal formulations, and bioactives (polyphenols, terpenes, and alkaloids) that can become potential therapeutics against PD with greater specificity, target approachability, bioavailability, and safety to the host. This information can be further utilized in the future to develop several value-added formulations and nutraceutical products to achieve the desired safety and efficacy for the management of PD. Full article
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