Antioxidant and Neuroprotective Effects of KM-34, A Novel Synthetic Catechol, Against Oxidative Stress-Induced Neurotoxicity

Drug Research ◽  
2017 ◽  
Vol 68 (05) ◽  
pp. 263-269 ◽  
Author(s):  
Yanier Nuñez-Figueredo ◽  
Jeney Ramirez-Sanchez ◽  
Yeniceis Issac ◽  
Estael Ochoa-Rodriguez ◽  
Yamila Verdecia-Reyes ◽  
...  
Keyword(s):  
Free Radicals ◽  
Cell Injury ◽  
Antioxidant Properties ◽  
Direct Reaction ◽  
Therapeutic Approaches ◽  
Neuroprotective Effects ◽  
Radical Reduction ◽  
Anti Oxidant ◽  
Brain Lipid Peroxidation

AbstractFree radicals are important mediators in a number of neurodegenerative diseases and molecules capable of scavenging reactive oxygen species (ROS) may be a feasible strategy for protecting neuronal cells. In this sense, polyphenols have been studied for their antioxidant effects, KM-34 (5-(3, 4-dydroxyl-benzylidene)-2, 2-dimethyl-1, 3-dioxane-4, 6-Dione) is a novel synthetic catechol with potential neuroprotective and antioxidant properties. We have assessed the antioxidant (as scavenging and iron-chelating compound) and neuroprotectant in vitro (in PC12 cell injury induced by H2O2, glutamate or FeSO4/AA) of KM-34. KM-34 was found to be a potent antioxidant, as shown by (i) inhibition of iron induced-brain lipid peroxidation, (ii) inhibition of 2-deoxyribose degradation, (iii) inhibition of superoxide radicals generation (IC50=11.04 μM) and (iv) inhibition of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical reduction (IC50=16.26 μM). The overall anti-oxidant action of KM-34 appears to be a combination of a direct reaction with free radicals and chelating the metal ions responsible for the production of ROS. Our work suggests that the antioxidant properties of KM-34 may provide future therapeutic approaches for neurodegenerative disorders.

scholarly journals Delivery of Thyronamines (TAMs) to the Brain: A Preliminary Study

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1616
Author(s):  
Nicoletta di Leo ◽  
Stefania Moscato ◽  
Marco Borso' ◽  
Simona Sestito ◽  
Beatrice Polini ◽  
...  
Keyword(s):  
High Performance ◽  
In Vitro Model ◽  
New Drugs ◽  
Therapeutic Approaches ◽  
Neuroprotective Effects ◽  
Pharmacological Response ◽  
Preliminary Study ◽  
Vitro Model ◽  
The Brain

Recent reports highlighted the significant neuroprotective effects of thyronamines (TAMs), a class of endogenous thyroid hormone derivatives. In particular, 3-iodothyronamine (T1AM) has been shown to play a pleiotropic role in neurodegeneration by modulating energy metabolism and neurological functions in mice. However, the pharmacological response to T1AM might be influenced by tissue metabolism, which is known to convert T1AM into its catabolite 3-iodothyroacetic acid (TA1). Currently, several research groups are investigating the pharmacological effects of T1AM systemic administration in the search of novel therapeutic approaches for the treatment of interlinked pathologies, such as metabolic and neurodegenerative diseases (NDDs). A critical aspect in the development of new drugs for NDDs is to know their distribution in the brain, which is fundamentally related to their ability to cross the blood–brain barrier (BBB). To this end, in the present study we used the immortalized mouse brain endothelial cell line bEnd.3 to develop an in vitro model of BBB and evaluate T1AM and TA1 permeability. Both drugs, administered at 1 µM dose, were assayed by high-performance liquid chromatography coupled to mass spectrometry. Our results indicate that T1AM is able to efficiently cross the BBB, whereas TA1 is almost completely devoid of this property.

In vitro antioxidant activity and phytochemical analyses of Acalypha godseffiana (Euphobiaceae) leaf extracts

2021 ◽  
Vol 25 (1) ◽  
pp. 75-79
Author(s):  
S.O. Olubodun ◽  
G.E. Eriyamremu ◽  
M.E. Ayevbuomwan ◽  
C.I. Nzoputa
Keyword(s):  
Antioxidant Activities ◽  
Radical Scavenging Activity ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Antioxidant Vitamin ◽  
Phytochemical Analysis ◽  
Leaf Extracts ◽  
Anti Oxidant ◽  
In Vitro Antioxidant Activity

The presence of various bioactive components makes it necessary to analyse plants for their potential to act as a source of useful treatments and cures for many inflammatory, infectious and pathogenic diseases. This study was carried out to determine phytochemicals and in-vitro antioxidant activities of the leaf extracts of Acalypha godseffiana. The leaves of A. godseffiana were collected, dried, pulverized and extracted separately with methanol and water using maceration method. The extract was concentrated in vacuo with rotary evaporator at 40oC. The extracts were subjected to quantitative phytochemical analysis and different anti-oxidant analytical procedures like FRAP, DPPH etc to determine the radical scavenging capabilities. The results of phytochemical analysis estimated the quantities and revealed the presence of alkaloids, flavonoids, tannins, saponins and terpenoids which varied in both extracts. The methanol and aqueous extracts exhibited antioxidant activities with relatively high IC50 (IC50 = 3.67 ìg/ml and 4.42ìg/ml respectively) which accounted for a low free radical-scavenging activity when compared with the reference antioxidant, vitamin C (IC50 = 1.51ìg/ml). The results of the study indicates that A. godseffiana leaf extracts contain secondary metabolites and possesses antioxidant properties.

scholarly journals Sodium Butyrate Protects N2a Cells against Aβ Toxicity In Vitro

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Jingxuan Sun ◽  
Boyu Yuan ◽  
Yancheng Wu ◽  
Yuhong Gong ◽  
Wenjin Guo ◽  
...  
Keyword(s):  
Sodium Butyrate ◽  
Cell Injury ◽  
Cell Damage ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Fatty Acid Salt ◽  
Cognitive Improvement ◽  
N2a Cells ◽  
Underlying Mechanisms

Alzheimer’s disease (AD) is a common neurodegenerative disease. Aβ plays an important role in the pathogenesis of AD. Sodium butyrate (NaB) is a short-chain fatty acid salt that exerts neuroprotective effects such as anti-inflammatory, antioxidant, antiapoptotic, and cognitive improvement in central nervous system diseases. The aim of this study is to research the protective effects of NaB on neurons against Aβ toxicity and to uncover the underlying mechanisms. The results showed that 2 mM NaB had a significant improvement effect on Aβ-induced N2a cell injury, by increasing cell viability and reducing ROS to reduce injury. In addition, by acting on the GPR109A receptor, NaB regulates the expression of AD-related genes such as APP, NEP, and BDNF. Therefore, NaB protects N2a cells from Aβ-induced cell damage through activating GPR109A, which provides an innovative idea for the treatment of AD.

scholarly journals Exogenous Carbon Monoxide Produces Rapid Antidepressant- and Anxiolytic-Like Effects

2021 ◽  
Vol 12 ◽  
Author(s):  
Yixiao Luo ◽  
Rafi Ullah ◽  
Jinfeng Wang ◽  
Yuru Du ◽  
Shihao Huang ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Cell Injury ◽  
Dorsal Hippocampus ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Gas Treatment ◽  
Promising Therapeutic Target ◽  
Co Gas

Carbon monoxide (CO), a byproduct of heme catalyzed by heme oxygenase (HO), has been reported to exert antioxidant and anti-inflammatory actions, and to produce significant neuroprotective effects. The potential effects of CO and even HO on depressive-like behaviors are still poorly understood. Utilizing several approaches including adeno-associated virus (AAV)-mediated overexpression of HO-1, systemic CO-releasing molecules (CO-RMs), CO-rich saline or CO gas treatment procedures in combination with hydrogen peroxide (H2O2)-induced PC12 cell injury model, and lipopolysaccharide (LPS)-induced depression mouse model, the present study aimed to investigate the potential antidepressant- and anxiolytic-like effects of endogenous and exogenous CO administration in vivo and in vitro. The results of in vitro experiments showed that both CO-RM-3 and CO-RM-A1 pretreatment blocked H2O2-induced cellular injuries by increasing cell survival and decreasing cell apoptosis and necrosis. Similar to the effects of CO-RM-3 and CO-RM-A1 pretreatment, AAV-mediated HO-1 overexpression in the dorsal hippocampus produced significant antidepressant-like activities in mice under normal conditions. Further investigation showed that the CO gas treatment significantly blocked LPS-induced depressive- and anxiety-like behaviors in mice. Taken together, our results suggest that the activation of HO-1 and/or exogenous CO administration produces protective effects and exerts antidepressant- and anxiolytic-like effects. These data uncover a novel function of the HO-1/CO system that appears to be a promising therapeutic target for the treatment of depression and anxiety.

scholarly journals Isomeric O-methyl cannabidiolquinones with dual BACH1/NRF2 activity

2020 ◽  
Author(s):  
Laura Casares ◽  
Juan Diego Unciti ◽  
Maria Eugenia Prados ◽  
Diego Caprioglio ◽  
Maureen Higgins ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Neurodegenerative Diseases ◽  
Cell Models ◽  
Therapeutic Approaches ◽  
Neuroprotective Effects ◽  
Anti Oxidant ◽  
Anti Inflammatory ◽  
The Brain

ABSTRACTOxidative stress and inflammation in the brain are two key hallmarks of neurodegenerative diseases (NDs) such as Alzheimer’s, Parkinson’s, Huntington’s and multiple sclerosis. The axis NRF2-BACH1 has anti-inflammatory and anti-oxidant properties that could be exploited pharmacologically to obtain neuroprotective effects. Activation of NRF2 or inhibition of BACH1 are, individually, promising therapeutic approaches for NDs. Compounds with dual activity as NRF2 activators and BACH1 inhibitors, could therefore potentially provide a more robust antioxidant and anti-inflammatory effects, with an overall better neuroprotective outcome. The phytocannabinoid cannabidiol (CBD) inhibits BACH1 but lacks significant NRF2 activating properties. Based on this scaffold, we have developed a novel CBD derivative that is highly effective at both inhibiting BACH1 and activating NRF2. This new CBD derivative provides neuroprotection in cell models of relevance to Huntington’s disease, setting the basis for further developments in vivo.

scholarly journals New Promising Therapeutic Avenues of Curcumin in Brain Diseases

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 236
Author(s):  
Tarek Benameur ◽  
Giulia Giacomucci ◽  
Maria Antonietta Panaro ◽  
Melania Ruggiero ◽  
Teresa Trotta ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Curcuma Longa ◽  
Brain Diseases ◽  
Neuroprotective Effects ◽  
Parkinson’S Diseases ◽  
Brain Structure And Function ◽  
Anti Oxidant ◽  
And Function

Curcumin, the dietary polyphenol isolated from Curcuma longa (turmeric), is commonly used as an herb and spice worldwide. Because of its bio-pharmacological effects curcumin is also called “spice of life”, in fact it is recognized that curcumin possesses important proprieties such as anti-oxidant, anti-inflammatory, anti-microbial, antiproliferative, anti-tumoral, and anti-aging. Neurodegenerative diseases such as Alzheimer’s Diseases, Parkinson’s Diseases, and Multiple Sclerosis are a group of diseases characterized by a progressive loss of brain structure and function due to neuronal death; at present there is no effective treatment to cure these diseases. The protective effect of curcumin against some neurodegenerative diseases has been proven by in vivo and in vitro studies. The current review highlights the latest findings on the neuroprotective effects of curcumin, its bioavailability, its mechanism of action and its possible application for the prevention or treatment of neurodegenerative disorders.

scholarly journals Impact of Seaweed-derived Xanthophyll Carotenoid on Obesity Management: Overview of the Last Decade

2020 ◽  
Author(s):  
Oyindamola Vivian Ojulari ◽  
Seul Gi Lee ◽  
Ju-Ock Nam
Keyword(s):  
Biological Activities ◽  
Antioxidant Properties ◽  
In Vivo Studies ◽  
Health Issues ◽  
Major Health ◽  
Chemical Treatments ◽  
Anti Oxidant ◽  
Published Research

Present-day lifestyles associated with high calorie-fat intake and accumulation, as well as energy imbalance, has led to the development of obesity and its comorbidities, which have emerged as some of the major health issues globally. To combat the disease, many studies have reported the anti-obesity effects of natural compounds in foods, with some advantages over chemical treatments. Carotenoids, particularly xanthophyll derived from seaweeds, have attracted the attention of researchers due to their notable biological activities, which are associated mainly with their antioxidant properties. Their involvement in oxidative stress modulation, regulation of major transcription factors and enzymes as well as their antagonistic effects on various obesity parameters have been examined in both in-vitro and in-vivo studies. The present review is a collation of published research over the last decade on the anti-oxidant properties of seaweed xanthophyll carotenoids, with a focus on fucoxanthin and astaxanthin and their mechanisms of action in obesity prevention and treatment.

scholarly journals Free Radicals and Neonatal Brain Injury: From Underlying Pathophysiology to Antioxidant Treatment Perspectives

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 2012
Author(s):  
Silvia Martini ◽  
Laura Castellini ◽  
Roberta Parladori ◽  
Vittoria Paoletti ◽  
Arianna Aceti ◽  
...  
Keyword(s):  
Free Radicals ◽  
Free Radical ◽  
Brain Injury ◽  
Antioxidant Properties ◽  
Standard Of Care ◽  
Antioxidant Defenses ◽  
Therapeutic Approaches ◽  
Neonatal Brain ◽  
Neonatal Brain Injury ◽  
Cerebrovascular Autoregulation

Free radicals play a role of paramount importance in the development of neonatal brain injury. Depending on the pathophysiological mechanisms underlying free radical overproduction and upon specific neonatal characteristics, such as the GA-dependent maturation of antioxidant defenses and of cerebrovascular autoregulation, different profiles of injury have been identified. The growing evidence on the detrimental effects of free radicals on the brain tissue has led to discover not only potential biomarkers for oxidative damage, but also possible neuroprotective therapeutic approaches targeting oxidative stress. While a more extensive validation of free radical biomarkers is required before considering their use in routine neonatal practice, two important treatments endowed with antioxidant properties, such as therapeutic hypothermia and magnesium sulfate, have become part of the standard of care to reduce the risk of neonatal brain injury, and other promising therapeutic strategies are being tested in clinical trials. The implementation of currently available evidence is crucial to optimize neonatal neuroprotection and to develop individualized diagnostic and therapeutic approaches addressing oxidative brain injury, with the final aim of improving the neurological outcome of this population.

scholarly journals Protective Effects of Aqueous Extract ofLuehea divaricataagainst Behavioral and Oxidative Changes Induced by 3-Nitropropionic Acid in Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Aline Alves Courtes ◽  
Letícia Priscila Arantes ◽  
Rômulo Pillon Barcelos ◽  
Ingrid Kich da Silva ◽  
Aline Augusti Boligon ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Aqueous Extract ◽  
Antioxidant Properties ◽  
Male Rats ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Nitropropionic Acid ◽  
3 Nitropropionic Acid

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease. Accordingly, 3-nitropropionic acid (3-NP) has been found to effectively produce HD-like symptoms.Luehea divaricata(L. divaricata), popularly known in Brazil as “açoita-cavalo,” may act as a neuroprotective agentin vitroandin vivo. We evaluated the hypothesis that the aqueous extract ofL. divaricatacould prevent behavioral and oxidative alterations induced by 3-NP in rats. 25 adult Wistar male rats were divided into 5 groups: (1) control, (2)L. divaricata(1000 mg/kg), (3) 3-NP, (4)L. divaricata(500 mg/kg) + 3-NP, and (5)L. divaricata(1000 mg/kg) + 3-NP. Groups 2, 4, and 5 receivedL. divaricatavia intragastric gavage daily for 10 days. Animals in groups 3, 4, and 5 received 20 mg/kg 3-NP daily from days 8–10. At day 10, parameters of locomotor activity and biochemical evaluations were performed. Indeed, rats treated with 3-NP showed decreased locomotor activity compared to controls. Additionally, 3-NP increased levels of reactive oxygen species and lipid peroxidation and decreased ratio of GSH/GSSG and acetylcholinesterase activity in cortex and/or striatum. Our results suggest that rats pretreated withL. divaricataprior to 3-NP treatment showed neuroprotective effects when compared to 3-NP treated controls, which may be due to its antioxidant properties.

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