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Chalcones belong to a class of biologically active polyphenolic natural products. As a result of their simple chemical nature, they are easily synthesized and show a variety of promising biological activities. 2-Hydroxy-4'-methoxychalcone (AN07) is a synthetic chalcone derivate with potential anti-atherosclerosis effects. In this study, we demonstrated the novel antioxidant, anti-inflammatory, and neuroprotective effects of AN07. In RAW 264.7 macrophages, AN07 attenuated lipopolysaccharide (LPS)-induced elevations in reactive oxygen species (ROS) level and oxidative stress via down-regulating gp91 phox expression and stimulating the antioxidant system of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) pathways, which were accompanied by increased glutathione (GSH) levels. Additionally, AN07 attenuated LPS-induced inflammatory factors, including NO, inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and phosphorylated inhibitor of nuclear factor kappa B-alpha (p-IκBα) in RAW 264.7 macrophages. However, the effects of AN07 on promoting nuclear Nrf2 levels and decreasing COX-2 expressions were significantly abrogated by the peroxisome proliferator-activated receptor-γ (PPARγ) antagonist GW9662. In human dopaminergic SH-SY5Y cells treated with or without methylglyoxal (MG), a toxic endogenous by-product of glycolysis, AN07 up-regulated neurotrophic signals including insulin-like growth factor 1 receptor (IGF-1R), p -Akt, p -GSK3β, glucagon-like peptide 1 receptor (GLP-1R), and brain-derived neurotrophic factor (BDNF). AN07 attenuated MG-induced apoptosis by up-regulating the B-cell lymphoma 2 (Bcl-2) protein and down-regulating the cytosolic expression of cytochrome c. AN07 also attenuated MG-induced neurite damage via down-regulating the Rho-associated protein kinase 2 (ROCK2)/phosphorylated LIM kinase 1 (p-LIMK1) pathway. Moreover, AN07 ameliorated the MG-induced down-regulation of neuroprotective Parkinsonism-associated proteins parkin , pink1 , and DJ-1 . These findings suggest that AN07 possesses the potentials to be an anti-inflammatory, antioxidant, and neuroprotective agent.

Glutamate neurotoxicity has been implicated in neuronal death in both acute CNS injury and in chronic neurodegenerative diseases. Five unique cyclic depsipeptides with neuroprotective activity, colletotrichamides A-E ( 1 - 5 ), were isolated from cultures of a halophyte Suaeda japonica -associated fungus, Colletotrichum gloeosporioides JS419. Spectroscopic analysis revealed that they were glycosylated cyclic lipodepsipeptides. Their relative configurations were determined by ROESY and J -based configuration analysis, and absolute configurations were established by chemical reactions including modified Mosher's method, advanced Marfey's method, and sugar derivatization. This is the first report of a glycosylated dimethyl-trioxygenated dodecanoyl moiety, and the relative as well as absolute stereochemistry was elucidated herein for the first time. Colletotrichamide C exhibited strong neuroprotective activity against glutamate in hippocampal HT22 cells.

Brain microvascular endothelial cell (BMEC) injury induced by ischemia-reperfusion (I/R) is the initial stage of blood-brain barrier (BBB) disruption, which results in a poor prognosis in ischemic stroke patients. Autophagy has been shown to have protective effects on BMECs against cerebral ischemic insults. However, molecular mechanism of BMEC autophagy during I/R is unclear. Long noncoding RNAs (lncRNAs) are emerging as new factors involved in cell autophagy. LncRNA Malat1 is one of the most highly upregulated I/R or OGD/R-responsive endothelial lncRNA and plays a protective role in BMECs against cerebral ischemic insults. Oxygen-glucose deprivation/reoxygenation (OGD/R) is used to mimic I/R injury in vitro. Based on these findings, we hypothesized that Malat1 might play a protective role by enhancing BMEC autophagy. We performed GFP-LC3 puncta formation, LC3 conversion, p62 expression, and cell death assays, and the results were consistent with our hypothesis that Malat1 promoted BMEC autophagy and survival under OGD/R condition. We further explored the molecular mechanisms by which Malat1 exerted regulatory effects, and found that Malat1 served as an endogenous sponge to downregulate miR-26b expression by binding directly to miR-26b. Furthermore, Malat1 overturned the inhibitory effect of miR-26b on BMEC autophagy and survival, which involved in promoting the expression of miR-26b target ULK2. Collectively, our study illuminated a new Malat1-miR-26b-ULK2 regulatory axis in which Malat1 served as a competing endogenous RNA by sponging miR-26b and upregulating ULK2 expression, thereby promoting BMEC autophagy and survival under OGD/R condition., (Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.)

Whereas the anti-inflammatory properties and mechanisms of action of long chain ω3 PUFAs have been abundantly investigated, research gaps remain regarding the respective contribution and mechanisms of action of their oxygenated metabolites collectively known as oxylipins. We conducted a dose-dependent and comparative study in human primary macrophages aiming to compare the anti-inflammatory activity of two types of DHA-derived oxylipins including the well-described protectins (NPD1 and PDX), formed through lipoxygenase pathway and the neuroprostanes (14-A 4t - and 4-F 4t -NeuroP) formed through free-radical mediated oxygenation and expected to be new anti-inflammatory mediators. Considering the potential ability of these DHA-derived oxylipins to bind PPARs and knowing the central role of these transcription factors in the regulation of macrophage inflammatory response, we performed transactivation assays to compare the ability of protectins and neuroprostanes to activate PPARs. All molecules significantly reduced mRNA levels of cytokines such as IL-6 and TNF-α, however not at the same doses. NPD1 showed the most effect at 0.1µM (-14.9%, p<0.05 for IL-6 and -26.7%, p<0.05 for TNF-α) while the three other molecules had greater effects at 10µM, with the strongest result due to the cyclopentenone neuroprostane, 14-A 4t -NeuroP (-49.8%, p<0.001 and -40.8%, p<0.001, respectively). Part of the anti-inflammatory properties of the DHA-derived oxylipins investigated could be linked to their activation of PPARs. Indeed, all tested oxylipins significantly activated PPARγ, with 14-A 4t -NeuroP leading to the strongest activation, and NPD1 and PDX also activated PPARα. In conclusion, our results show that neuroprostanes and more especially cyclopentenone neuroprostanes have potent anti-inflammatory activities similar or even more pronounced than protectins supporting that neuroprostanes should be considered as important contributors to the anti-inflammatory effects of DHA., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Parkinson's disease (PD) is one of the most common neurodegenerative disorders and is characterized by loss of dopaminergic neurons in the substantia nigra (SN). Although the causes of PD are not understood, evidence suggests that oxidative stress, mitochondrial dysfunction, and inflammation are associated with its pathogenesis. Morin (3,5,7,2',4'-pentahydroxyflavone) is a flavonol found in wine and many herbs and fruits. Previous studies have suggested that morin prevents oxidative damage and inflammation and ameliorates mitochondrial dysfunction. The present study describes the neuroprotective effects of morin in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD, and we report the results of our investigation into its neuroprotective mechanism in primary neurons and astrocytes. In the mouse model, morin pretreatment ameliorated motor dysfunction, protected against dopaminergic neuronal losses in SN and striatum, and alleviated MPTP-induced astrocyte activation. In vitro studies revealed that morin protected primary cultured neurons against 1-methyl-4-phenylpyridine (MPP(+) )-mediated reactive oxygen species production and mitochondrial membrane potential (MMP) disruption. In addition, morin effectively reduced MPP(+) -induced astroglial activation and nuclear translocation of nuclear factor-κB in primary cultured astrocytes. These results indicate that morin acts via multiple neuroprotective mechanisms in our mouse model and suggest that morin be viewed as a potential treatment and preventative for PD. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

The purpose of the work was to assess the influence of the concentrate of red table wine Saperavi on the cultivated nerve cells exposed to glutamate. The selection of Saperavi as the source of phenolic compounds was not accidental: this type of grapes in the Krasnodar region has the highest content of them - up to 4-5 g/dm3 and more. Polyphenol concentrate was prepared by pre-distillation of ethanol using vacuum, evaporation of red table wine with a rotary vaporizer, with the subsequent lyophilic drying. By the methods of voltammetry and chemiluminescence an antioxidant activity, and a quantity of antioxidants in the concentrate have been determined. By HPLC it was established that a large group of phenolic compounds with high antioxidant activity was present in the concentrate of polyphenols: procyanidins (total concentration up to 425 mg/dm3), quercetin (21.8-32.6 mg/dm3), gallic acid (124.2-164.7 mg/dm3), resveratrol (6.26-13.22 mg/dm3), catechins (1026 - 1480 mg/dm3). Effect of red wine Saperavi concentrate on glutamate cytotoxicity was studied in the neuron culture of the cerebellum of 7-9-day-old rats. It was shown that the presence of. antioxidants reduced the intensity of chemiluminescence in model systems that generate free radicals. It was established that quenching of chemiluminescence in the system <> composed 68.43%, and in the system of the yolk lipoproteins - 86.36%. The application of concentrate Saperavi significantly increased the survivability of neurons: at the doses 5, 10 and 30 mcg/ml the number of intact neurons was respectively 38.6; 41.5 and 37.1%. The dose 20 mcg/ml was the most effective - the proportion of live neurons comprised 47.4%. The obtained results can be explained by the high antioxidant activity of concentrate flavonoids, including high content of biologically active compounds - catechins, quercetin, rutin, resveratrol. Thus, the consumption of red wine in quantities that exclude harmful effects, can have a positive impact on human health and the brain in particular.

Hormones regulate homeostasis by communicating through the bloodstream to the body's organs, including the brain. As homeostatic regulators of brain function, some hormones exert neuroprotective actions. This is the case for the ovarian hormone 17β-oestradiol, which signals through oestrogen receptors (ERs) that are widely distributed in the male and female brain. Recent discoveries have shown that oestradiol is not only a reproductive hormone but also a brain-derived neuroprotective factor in males and females and that ERs coordinate multiple signalling mechanisms that protect the brain from neurodegenerative diseases, affective disorders and cognitive decline.