scholarly journals Inhibitory Effects of Auraptene and Naringin on Astroglial Activation, Tau Hyperphosphorylation, and Suppression of Neurogenesis in the Hippocampus of Streptozotocin-Induced Hyperglycemic Mice

Antioxidants ◽  
2018 ◽  
Vol 7 (8) ◽  
pp. 109 ◽  
Author(s):  
Satoshi Okuyama ◽  
Tatsumi Nakashima ◽  
Kumi Nakamura ◽  
Wakana Shinoka ◽  
Maho Kotani ◽  
...  
Keyword(s):  
Related Compound ◽  
Tau Hyperphosphorylation ◽  
Neuroprotective Agents ◽  
Inhibitory Effects ◽  
Peripheral Tissues ◽  
Anti Inflammatory ◽  
Astroglial Activation ◽  
The Brain ◽  
Antioxidant Effects ◽  
Extensive Damage

Auraptene, a citrus-related compound, exerts anti-inflammatory effects in peripheral tissues, and we demonstrated these effects in the brains of a lipopolysaccharide-injected systemic inflammation animal model and a brain ischemic mouse model. Naringin, another citrus-related compound, has been shown to exert antioxidant effects in several animal models. Hyperglycemia induces oxidative stress and inflammation and causes extensive damage in the brain; therefore, we herein evaluated the anti-inflammatory and other effects of auraptene and naringin in streptozotocin-induced hyperglycemic mice. Both compounds inhibited astroglial activation and the hyperphosphorylation of tau at 231 of threonine in neurons, and also recovered the suppression of neurogenesis in the dentate gyrus of the hippocampus in hyperglycemic mice. These results suggested that auraptene and naringin have potential effects as neuroprotective agents in the brain.

Carrageenan-induced brain inflammation

1986 ◽  
Vol 65 (5) ◽  
pp. 679-685 ◽  
Author(s):  
Daniel A. Gamache ◽  
John T. Povlishock ◽  
Earl F. Ellis
Keyword(s):  
Arachidonic Acid ◽  
Vascular Permeability ◽  
Brain Inflammation ◽  
Intraventricular Injection ◽  
Arachidonic Acid Metabolite ◽  
Maximum Increase ◽  
Peripheral Tissues ◽  
Neutrophil Extravasation ◽  
Anti Inflammatory ◽  
The Brain

✓ Administration of the mucopolysaccharide, carrageenan (CAR), into the hind paw of the rat or mouse induces a local inflammation characterized by increased arachidonic acid metabolism, increased vascular permeability, edema, and neutrophil extravasation. Carrageenan-induced hind-paw inflammation is inhibited by prostaglandin synthesis inhibitors, and this assay predicts the clinical success of anti-inflammatory agents in reducing peripheral inflammation. The purpose of this study was to determine if intraventricular injection of CAR would induce brain inflammation similar to that evoked by CAR in peripheral tissues. The present study demonstrates that CAR injection into the ventricles of the mouse brain does in fact induce an inflammatory response very similar to that caused by injection of CAR into the peripheral tissues. The brain response to CAR was dose-dependent, with the maximum increase in cerebrovascular permeability to iodine-125-labeled human serum albumin and percent brain water occurring after injection of 50 µg CAR. As is seen in CAR-induced inflammation of the hind paw, the maximum increase in brain vascular permeability occurred 4 hours after CAR injection. Histological analysis of brains 4 hours after CAR administration showed global neutrophil extravasation into the subarachnoid space and evidence of focal neuronal swelling. Methotrexate-induced neutropenia, however, failed to diminish the permeability response to CAR. Gas chromatographic and mass spectrometric measurements of brain prostaglandins 4 hours after CAR injection revealed a significantly increased level of 6-keto-prostaglandin F1α. These results indicate that a significant increase in prostacyclin, the pro-inflammatory arachidonic acid metabolite, during CAR-induced brain inflammation is likely. These studies suggest that CAR-induced brain inflammation may be a useful model on which to test the efficacy of anti-inflammatory agents in the brain, as well as providing information concerning the mediators and mechanisms by which the brain may sustain inflammatory injury.

scholarly journals Behavioural Fever Promotes an Inflammatory Reflex Circuit in Ectotherms

2021 ◽  
Vol 22 (16) ◽  
pp. 8860
Author(s):  
Nataly Sanhueza ◽  
Ricardo Fuentes ◽  
Andrea Aguilar ◽  
Beatriz Carnicero ◽  
Karina Vega ◽  
...  
Keyword(s):  
Viral Infection ◽  
Inflammatory Responses ◽  
Expression Patterns ◽  
Inflammatory Factors ◽  
Peripheral Tissues ◽  
Network Activation ◽  
Entry Points ◽  
Anti Inflammatory ◽  
The Brain

Background: The communication between the brain and the immune system is a cornerstone in animal physiology. This interaction is mediated by immune factors acting in both health and pathogenesis, but it is unclear how these systems molecularly and mechanistically communicate under changing environmental conditions. Behavioural fever is a well-conserved immune response that promotes dramatic changes in gene expression patterns during ectotherms’ thermoregulatory adaptation, including those orchestrating inflammation. However, the molecular regulators activating the inflammatory reflex in ectotherms remain unidentified. Methods: We revisited behavioural fever by providing groups of fish a thermal gradient environment during infection. Our novel experimental setup created temperature ranges in which fish freely moved between different thermal gradients: (1) wide thermoregulatory range; T° = 6.4 °C; and (2) restricted thermoregulatory range; T° = 1.4 °C. The fish behaviour was investigated during 5-days post-viral infection. Blood, spleen, and brain samples were collected to determine plasmatic pro- and anti-inflammatory cytokine levels. To characterize genes’ functioning during behavioural fever, we performed a transcriptomic profiling of the fish spleen. We also measured the activity of neurotransmitters such as norepinephrine and acetylcholine in brain and peripheral tissues. Results: We describe the first set of the neural components that control inflammatory modulation during behavioural fever. We identified a neuro-immune crosstalk as a potential mechanism promoting the fine regulation of inflammation. The development of behavioural fever upon viral infection triggers a robust inflammatory response in vivo, establishing an activation threshold after infection in several organs, including the brain. Thus, temperature shifts strongly impact on neural tissue, specifically on the inflammatory reflex network activation. At the molecular level, behavioural fever causes a significant increase in cholinergic neurotransmitters and their receptors’ activity and key anti-inflammatory factors such as cytokine Il10 and Tgfβ in target tissues. Conclusion: These results reveal a cholinergic neuronal-based mechanism underlying anti-inflammatory responses under induced fever. We performed the first molecular characterization of the behavioural fever response and inflammatory reflex activation in mobile ectotherms, identifying the role of key regulators of these processes. These findings provide genetic entry points for functional studies of the neural–immune adaptation to infection and its protective relevance in ectotherm organisms.

scholarly journals Neuroprotective and Anti-Microglial Activation Effects of Tocotrienols in Brains of Lipopolysaccharide-Induced Inflammatory Model Mice

Neuroglia ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 89-97
Author(s):  
Satoshi Okuyama ◽  
Masafumi Matsuda ◽  
Yuna Okusako ◽  
Sanae Miyauchi ◽  
Toshiki Omasa ◽  
...  
Keyword(s):  
Microglial Activation ◽  
Inflammatory Responses ◽  
Neuronal Cell ◽  
Vesicle Membrane ◽  
Peripheral Tissues ◽  
Cell Dysfunction ◽  
Stratum Lucidum ◽  
The Central Nervous System ◽  
Anti Inflammatory ◽  
The Brain

Inflammation is the cause and/or result of many diseases in peripheral tissues and the central nervous system. Recent findings suggested that inflammation in peripheral tissue induces an inflammatory response in the brain that activates glial cells, which, in turn, induce neuronal cell dysfunction. Therefore, anti-inflammatory compounds are important for the suppression of chronic inflammation and prevention of disease. The present study revealed microglial activation in the hippocampus of the brain two days after the peripheral administration of lipopolysaccharide (LPS). Furthermore, the expression of the synaptic vesicle membrane protein, synaptophysin, in the CA3 stratum lucidum of the hippocampus was down-regulated 7 days after the LPS injection. The administration of tocotrienols, a type of vitamin E, significantly attenuated these changes in the hippocampus. Collectively, the present results demonstrated the spread of peripheral inflammatory responses to the brain, in which glial activation and neuronal dysfunction were induced, while tocotrienols exerted anti-inflammatory effects and protected neurons from damage.

Design, Synthesis and Pharmacological Evaluation of Novel Antiinflammatory and Analgesic O-Benzyloxime Compounds Derived From Natural Eugenol

2019 ◽  
Vol 16 (10) ◽  
pp. 1157-1166
Author(s):  
Rodrigo César da Silva ◽  
Fabiano Veiga ◽  
Fabiana Cardoso Vilela ◽  
André Victor Pereira ◽  
Thayssa Tavares da Silva Cunha ◽  
...  
Keyword(s):  
Formalin Test ◽  
Docking Studies ◽  
Paw Edema ◽  
Inhibitory Effects ◽  
Structural Pattern ◽  
Design Synthesis ◽  
Drug Candidates ◽  
Anti Inflammatory ◽  
Analgesic Activities ◽  
Cox 1

Background: : A new series of O-benzyloximes derived from eugenol was synthesized and was evaluated for its antinociceptive and anti-inflammatory properties. Methods: : The target compounds were obtained in good global 25-28% yields over 6 steps, which led us to identify compounds (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-(4- (methylthio)benzyloxime (8b), (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-4- bromobenzyloxime (8d) and (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-4- (methylsulfonyl)benzyloxime (8f) as promising bioactive prototypes. Results:: These compounds have significant analgesic and anti-inflammatory effects, as evidenced by formalin-induced mice paw edema and carrageenan-induced mice paw edema tests. In the formalin test, compounds 8b and 8f evidenced both anti-inflammatory and direct analgesic activities and in the carrageenan-induced paw edema, with compounds 8c, 8d, and 8f showing the best inhibitory effects, exceeding the standard drugs indomethacin and celecoxib. Conclusion: : Molecular docking studies have provided additional evidence that the pharmacological profile of these compounds may be related to inhibition of COX enzymes, with slight preference for COX-1. These results led us to identify the new O-benzyloxime ethers 8b, 8d and 8f as orally bioactive prototypes, with a novel structural pattern capable of being explored in further studies aiming at their optimization and development as drug candidates.

Assessment of Cota altissima (L.) J. Gay for phytochemical composition and antioxidant, anti-inflammatory, antidiabetic and antimicrobial activities

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Gamze Göger ◽  
Muhammed Allak ◽  
Ali Şen ◽  
Fatih Göger ◽  
Mehmet Tekin ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Essential Oil ◽  
Antioxidant Activities ◽  
Antimicrobial Activities ◽  
Antidiabetic Activity ◽  
Gram Negative Bacteria ◽  
Inhibitory Effects ◽  
Dicaffeoylquinic Acid ◽  
Anti Inflammatory ◽  
Phytochemical Profiles

Abstract Phytochemical profiles of essential oil (EO), fatty acids, and n-hexane (CAH), diethyl ether (CAD), ethyl acetate (CAE) and methanol extracts (CAM) of Cota altissima L. J. Gay (syn. Anthemis altissima L.) were investigated as well as their antioxidant, anti-inflammatory, antidiabetic and antimicrobial activites. The essential oil was characterized by the content of acetophenone (35.8%) and β-caryophyllene (10.3%) by GC-MS/FID. Linoleic and oleic acid were found as main fatty acids. The major constituents of the extracts were found to be 5-caffeoylquinic acid, 3,5-dicaffeoylquinic acid, isorhamnetin glucoside, quercetin and quercetin glucoside by LC-MS/MS. Antioxidant activities of the extracts were determined by scavenging of DPPH and ABTS free radicals. Also, the inhibitory effects on lipoxygenase and α-glucosidase enzymes were determined. Antimicrobial activity was evaluated against Gram positive, Gram negative bacteria and yeast pathogens. CAM showed the highest antioxidant activity against DPPH and ABTS radicals with IC50 values of 126.60 and 144.40 μg/mL, respectively. In the anti-inflammatory activity, CAE demonstrated the highest antilipoxygenase activity with an IC50 value of 105.40 μg/mL, whereas, CAD showed the best inhibition of α-glucosidase with an IC50 value of 396.40 μg/mL in the antidiabetic activity. CAH was effective against Staphylococcus aureus at MIC = 312.5 µg/mL. This is the first report on antidiabetic, anti-inflammatory and antimicrobial activities of different extracts of C. altissima.

scholarly journals Anti-Inflammatory and Antioxidant Effects of Dietary Supplementation and Lifestyle Factors

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 371
Author(s):  
Llion Arwyn Roberts ◽  
Katsuhiko Suzuki
Keyword(s):  
Dietary Supplementation ◽  
Lifestyle Factors ◽  
Anti Inflammatory ◽  
Antioxidant Effects

Trends relating to specific diets and lifestyle factors like physical (in) activity have formed in recent times [...]

scholarly journals Modeling temperature- and Cav3 subtype-dependent alterations in T-type calcium channel mediated burst firing

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Fernando R. Fernandez ◽  
Mircea C. Iftinca ◽  
Gerald W. Zamponi ◽  
Ray W. Turner
Keyword(s):  
Calcium Channel ◽  
Neuronal Excitability ◽  
Neuronal Firing ◽  
Mammalian Brain ◽  
Peripheral Tissues ◽  
Window Current ◽  
Modeling Data ◽  
The Brain ◽  
Firing Neuron ◽  
Cav3 Channel

AbstractT-type calcium channels are important regulators of neuronal excitability. The mammalian brain expresses three T-type channel isoforms (Cav3.1, Cav3.2 and Cav3.3) with distinct biophysical properties that are critically regulated by temperature. Here, we test the effects of how temperature affects spike output in a reduced firing neuron model expressing specific Cav3 channel isoforms. The modeling data revealed only a minimal effect on baseline spontaneous firing near rest, but a dramatic increase in rebound burst discharge frequency for Cav3.1 compared to Cav3.2 or Cav3.3 due to differences in window current or activation/recovery time constants. The reduced response by Cav3.2 could optimize its activity where it is expressed in peripheral tissues more subject to temperature variations than Cav3.1 or Cav3.3 channels expressed prominently in the brain. These tests thus reveal that aspects of neuronal firing behavior are critically dependent on both temperature and T-type calcium channel subtype.

scholarly journals UBE4B, a microRNA-9 target gene, promotes autophagy-mediated Tau degradation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Manivannan Subramanian ◽  
Seung Jae Hyeon ◽  
Tanuza Das ◽  
Yoon Seok Suh ◽  
Yun Kyung Kim ◽  
...  
Keyword(s):  
Mouse Model ◽  
Ubiquitin Ligase ◽  
Therapeutic Approach ◽  
Target Gene ◽  
Neuroblastoma Cells ◽  
E3 Ligase ◽  
Tau Hyperphosphorylation ◽  
Phosphorylated Tau ◽  
Major Pathway ◽  
The Brain

AbstractThe formation of hyperphosphorylated intracellular Tau tangles in the brain is a hallmark of Alzheimer’s disease (AD). Tau hyperphosphorylation destabilizes microtubules, promoting neurodegeneration in AD patients. To identify suppressors of tau-mediated AD, we perform a screen using a microRNA (miR) library in Drosophila and identify the miR-9 family as suppressors of human tau overexpression phenotypes. CG11070, a miR-9a target gene, and its mammalian orthologue UBE4B, an E3/E4 ubiquitin ligase, alleviate eye neurodegeneration, synaptic bouton defects, and crawling phenotypes in Drosophila human tau overexpression models. Total and phosphorylated Tau levels also decrease upon CG11070 or UBE4B overexpression. In mammalian neuroblastoma cells, overexpression of UBE4B and STUB1, which encodes the E3 ligase CHIP, increases the ubiquitination and degradation of Tau. In the Tau-BiFC mouse model, UBE4B and STUB1 overexpression also increase oligomeric Tau degradation. Inhibitor assays of the autophagy and proteasome systems reveal that the autophagy-lysosome system is the major pathway for Tau degradation in this context. These results demonstrate that UBE4B, a miR-9 target gene, promotes autophagy-mediated Tau degradation together with STUB1, and is thus an innovative therapeutic approach for AD.

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