The metabolite GLP‐1 (9‐36) is neuroprotective and anti‐inflammatory in cellular models of neurodegeneration

The positive effects of mesenchymal stem cells (MSCs) are primarily activated through molecular secretions known as paracrine activity, which regulates the function of various cell types including immune cells. Accumulating evidence shows that exosomes of soluble factors released from MSCs are potential alternative agents for stem cell-based therapy, although the exact underlying mechanism has not been elucidated. The purpose of this study was to evaluate the potential effects of exosomes produced by adipose-derived MSCs and to examine the changes in anti-inflammatory genes in concurrence with the polarization of M2 macrophages in cellular models ex vivo. Isolated exosomes were used to investigate the inflammatory modulation in pro-inflammatory cytokine-treated fibroblasts and THP-1 cells. The anti-inflammatory mRNA expression associated with M2 macrophages was significantly upregulated after exosome treatment in an interferon gamma and tumor necrosis factor alpha-treated inflammatory environment. Furthermore, melatonin-stimulated exosomes exerted superior anti-inflammatory modulation via exosomal miRNAs miR-34a, miR-124, and miR-135b, compared with exosomes. Our results indicate that melatonin-stimulated exosomes originating from adipose-derived MSCs are safe and efficient tools for regenerative medicine to treat inflammatory diseases.

Download Full-text

Drug screens of NGLY1 Deficiency worm and fly models reveal catecholamine, NRF2 and anti-inflammatory pathway activation as clinical approaches

10.1101/563478 ◽

2019 ◽

Author(s):

Sangeetha Iyer ◽

Joshua D. Mast ◽

Hillary Tsang ◽

Tamy P. Rodriguez ◽

Nina DiPrimio ◽

...

Keyword(s):

Human Cell ◽

Gene Networks ◽

Transcriptional Regulator ◽

Model Organisms ◽

Dopamine Receptor Agonist ◽

Lead Discovery ◽

Larval Size ◽

Toxic Dose ◽

Cellular Models ◽

Anti Inflammatory

AbstractN-glycanase 1/NGLY1 Deficiency is an ultra-rare and complex monogenic glycosylation disorder that affects fewer than 40 patients globally. NGLY1 Deficiency has been studied in model organisms such as yeast, worms, flies and mice. Proteasomal and mitochondrial homeostasis gene networks are controlled by the evolutionarily conserved transcriptional regulator Nrf1, whose activity requires deglycosylation by NGLY1. Hypersensitivity to the proteasome inhibitor bortezomib is a common phenotype observed in whole animal and cellular models of NGLY1 Deficiency. Here we describe unbiased phenotypic drug screens to identify FDA approved drugs, generally recognized as safe natural products and novel chemical entities that rescue growth and development of NGLY1-deficient worm and fly larvae treated with a toxic dose of bortezomib. We used image-based larval size and number assays for use in screens of a 2,560-member drug repurposing library and a 20,240-member lead discovery library. A total of 91 validated hit compounds from primary invertebrate screens were tested in a human cell line in a NRF2 activity assay. NRF2 is a transcriptional regulator that regulates cellular redox homeostasis and it can compensate for loss of Nrf1. Plant-based polyphenols comprise the largest class of hit compounds and NRF2 inducers. Catecholamines and catecholamine receptor activators comprise the second largest class of hits. Steroidal and non-steroidal anti-inflammatory drugs comprise the third largest class. Only one compound was active in all assays and species: the atypical antipsychotic and dopamine receptor agonist aripiprazole. Worm and fly models of NGLY1 Deficiency validate therapeutic rationales for activation of NRF2 and anti-inflammatory pathways based on results in mice and human cell models and suggest a novel therapeutic rationale for boosting catecholamine levels and/or signaling in the brain.

Download Full-text

Phenolic Composition of Hydrophilic Extract of Manna from Sicilian Fraxinus angustifolia Vahl and its Reducing, Antioxidant and Anti-Inflammatory Activity in Vitro

Antioxidants ◽

10.3390/antiox8100494 ◽

2019 ◽

Vol 8 (10) ◽

pp. 494 ◽

Cited By ~ 5

Author(s):

Alessandro Attanzio ◽

Antonella D’Anneo ◽

Francesco Pappalardo ◽

Francesco Paolo Bonina ◽

Maria Antonia Livrea ◽

...

Keyword(s):

Disease Model ◽

Membrane Lipid ◽

In Vitro Assays ◽

Alcoholic Extract ◽

Cellular Models ◽

Reducing Ability ◽

Scavenger Activity ◽

Fraxinus Angustifolia ◽

Anti Inflammatory

Manna, a very singular vegetable product derived from the spontaneous solidification of the sap of some Fraxinus species, has long been known for its mild laxative and emollient properties. In this work, a hydro-alcoholic extract of manna (HME) from Sicilian Fraxinus angustifolia Vahl was investigated using HPLC-DAD to find phenol components and using chemical and biological in vitro assays to determine its reducing, antioxidant and anti-inflammatory capacity. We identified elenolic acid, tyrosol, hydroxytyrosol, catechin, fraxetin, verbascoside, gallic acid, procyanidin-B1, and luteolin 3,7 glucoside, in order of abundance. Measurements of total antioxidant activity by Folin-Ciocalteu reaction and ferric reducing ability (FRAP), as well as of scavenger activity towards ABTS•+, DPPH•, and perferryl-myoglobin radicals, showed that the phytocomplex effectively reduced oxidants with different standard potentials. When compared with vitamin E, HME also behaved as an efficient chain-breaking antioxidant against lipoperoxyl radicals from methyl linoleate. In cellular models for oxidative stress, HME counteracted membrane lipid oxidation of human erythrocytes stimulated by tert-butyl hydroperoxide and prevented the generation of reactive oxygen species, as well as the GSH decay in IL-1β–activated intestinal normal-like cells. Moreover, in this in vitro intestinal bowel disease model, HME reduced the release of the pro-inflammatory cytokines IL-6 and IL-8. These findings may suggest that manna acts as an antioxidant and anti-inflammatory natural product in humans, beyond its well-known effects against constipation.

Download Full-text

Anti-SASP and anti-inflammatory activity of resveratrol, curcumin and β-caryophyllene association on human endothelial and monocytic cells

Biogerontology ◽

10.1007/s10522-021-09915-0 ◽

2021 ◽

Author(s):

Giulia Matacchione ◽

Felicia Gurău ◽

Andrea Silvestrini ◽

Mattia Tiboni ◽

Luca Mancini ◽

...

Keyword(s):

Inflammatory Response ◽

Cell Line ◽

Nutritional Supplement ◽

Natural Compounds ◽

Monocytic Cell ◽

Monocytic Cell Line ◽

Expression Levels ◽

Cellular Models ◽

Research Fields ◽

Anti Inflammatory

AbstractA challenging and promising new branch of aging-related research fields is the identification of natural compounds able to modulate the senescence-associated secretory phenotype (SASP), which characterizes senescent cells and can contribute to fuel the inflammaging. We investigated both the anti-SASP and anti-inflammatory activities of a nutritional supplement, namely Fenoxidol™, composed of turmeric extract bioCurcumin (bCUR), Polydatin (the natural glycosylated precursor of Resveratrol-RSV), and liposomal β-caryophyllene (BCP), in two human cellular models, such as the primary endothelial cell line, HUVECs and the monocytic cell line, THP-1. Replicative and Doxorubicin-induced senescent HUVECs, both chosen as cellular models of SASP, and lipopolysaccharides (LPS)-stimulated THP-1, selected as a model of the inflammatory response, were treated with the three single natural compounds or with a combination of them (MIX). In both senescent HUVEC models, MIX treatment significantly reduced IL-1β and IL-6 expression levels and p16ink4a protein, and also increased SIRT1 protein level, as well as downregulated miR-146a and miR-21 expression, two of the so-called inflamma-miRNAs, more effectively than the single compounds. In THP-1 cells stimulated with LPS, the MIX showed a significant effect in decreasing IL-1β, IL-6, TNF-α, and miR-146a expression levels and Caspase-1 activation, in association with an up-regulation of SIRT1 protein, compared to the single compounds. Overall, our results suggest that the three analysed compounds can have a combined effect in restraining SASP in senescent HUVECs as well as the inflammatory response in LPS-stimulated THP-1 cells.

Download Full-text

Tabetri™ (Tabebuia avellanedae Ethanol Extract) Ameliorates Osteoarthritis Symptoms Induced by Monoiodoacetate through Its Anti-Inflammatory and Chondroprotective Activities

Mediators of Inflammation ◽

10.1155/2017/3619879 ◽

2017 ◽

Vol 2017 ◽

pp. 1-14 ◽

Cited By ~ 8

Author(s):

Jae Gwang Park ◽

Young-Su Yi ◽

Yo Han Hong ◽

Sulgi Yoo ◽

Sang Yun Han ◽

...

Keyword(s):

Cell Line ◽

Proinflammatory Cytokines ◽

Inflammatory Mediators ◽

Molecular Mechanisms ◽

Ethanol Extract ◽

Degenerative Joint Disease ◽

Joint Disease ◽

Cellular Models ◽

Anti Inflammatory

Although osteoarthritis (OA), a degenerative joint disease characterized by the degradation of joint articular cartilage and subchondral bones, is generally regarded as a degenerative rather than inflammatory disease, recent studies have indicated the involvement of inflammation in OA pathogenesis. Tabebuia avellanedae has long been used to treat various diseases; however, its role in inflammatory response and the underlying molecular mechanisms remain poorly understood. In this study, the pharmacological effects of Tabetri (Tabebuia avellanedae ethanol extract (Ta-EE)) on OA pathogenesis induced by monoiodoacetate (MIA) and the underlying mechanisms were investigated using experiments with a rat model and in vitro cellular models. In the animal model, Ta-EE significantly ameliorated OA symptoms and reduced the serum levels of inflammatory mediators and proinflammatory cytokines without any toxicity. The anti-inflammatory activity of Ta-EE was further confirmed in a macrophage-like cell line (RAW264.7). Ta-EE dramatically suppressed the production and mRNA expressions of inflammatory mediators and proinflammatory cytokines in lipopolysaccharide-stimulated RAW264.7 cells without any cytotoxicity. Finally, the chondroprotective effect of Ta-EE was examined in a chondrosarcoma cell line (SW1353). Ta-EE markedly suppressed the mRNA expression of matrix metalloproteinase genes. The anti-inflammatory and chondroprotective activities of Ta-EE were attributed to the targeting of the nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1) signaling pathways in macrophages and chondrocytes.

Download Full-text

Flavonoids as anti-inflammatory agents

Proceedings of The Nutrition Society ◽

10.1017/s002966511000162x ◽

2010 ◽

Vol 69 (3) ◽

pp. 273-278 ◽

Cited By ~ 208

Author(s):

Mauro Serafini ◽

Ilaria Peluso ◽

Anna Raguzzini

Keyword(s):

Related Factor ◽

Plant Foods ◽

Reactive Protein ◽

Cellular Models ◽

Chemical Structures ◽

Markers Of Inflammation ◽

Wide Range ◽

Anti Inflammatory

Epidemiological evidence suggests that a high intake of plant foods is associated with lower risk of chronic diseases. However, the mechanism of action and the components involved in this effect have not been identified clearly. In recent years, the scientific community has agreed to focus its attention on a class of secondary metabolites extensively present in a wide range of plant foods: the flavonoids, suggested as having different biological roles. The anti-inflammatory actions of flavonoids in vitro or in cellular models involve the inhibition of the synthesis and activities of different pro-inflammatory mediators such as eicosanoids, cytokines, adhesion molecules and C-reactive protein. Molecular activities of flavonoids include inhibition of transcription factors such as NF-κB and activating protein-1 (AP-1), as well as activation of nuclear factor-erythroid 2-related factor 2 (Nrf2). However, the in vitro evidence might be somehow of limited impact due to the non-physiological concentrations utilized and to the fact that in vivo flavonoids are extensively metabolized to molecules with different chemical structures and activities compared with the ones originally present in the food. Human studies investigating the effect of flavonoids on markers of inflammation are insufficient, and are mainly focused on flavonoid-rich foods but not on pure molecules. Most of the studies lack assessment of flavonoid absorption or fail to associate an effect on inflammation with a change in circulating levels of flavonoids. Human trials with appropriate placebo and pure flavonoid molecules are needed to clarify if flavonoids represent ancillary ingredients or key molecules involved in the anti-inflammatory properties of plant foods.

Download Full-text

51 Palmitoylethanolamide associated to polydatin reduces inflammation in human endothelial vascular cells exposed to doxorubicin and trastuzumab through PPAR-a and NLRP3-related pathways

European Heart Journal Supplements ◽

10.1093/eurheartj/suab130.006 ◽

2021 ◽

Vol 23 (Supplement_G) ◽

Author(s):

Vincenzo Quagliariello ◽

Martina Iovine ◽

Carlo Maurea ◽

Simona Buccolo ◽

Andrea Paccone ◽

...

Keyword(s):

Cell Viability ◽

Transcriptional Activation ◽

Nlrp3 Inflammasome ◽

Vascular Endothelial Cells ◽

Peroxisome Proliferator ◽

Membrane Phospholipids ◽

Peroxisome Proliferator Activated Receptor ◽

Endogenous Fatty Acid ◽

Cellular Models ◽

Anti Inflammatory

Abstract Aims Palmitoylethanolamide is an endogenous fatty acid mediator that is synthetized from membrane phospholipids by N-acyl phosphatidylethanolamine phospholipase D. Polydatin is a nutraceutical agent derived from trans-resveratrol with established anti-inflammatory and anti-atherogenic properties. We aimed to assess whether palmitoylethanolamide combined to polydatin, co-incubated during doxorubicin and trastuzumab, reduces anticancer drugs-related cardiotoxicity in cellular models. Methods Human vascular endothelial cells were exposed to subclinical concentration of doxorubicin (at 100 and 200 nM) combined to trastuzumab (at 100 and 200 nM) alone or in combination with a formulation composed by palmitoylethanolamide and polydatin (500 nM and 50 µM, respectively) for 48 h. After the incubation period, we performed the following tests: determination of cell viability, through analysis of mitochondrial dehydrogenase activity, study of lipid peroxidation (quantifying cellular Malondialdehyde and 4-hydroxynonenal), intracellular Ca2+ homeostasis. Moreover, pro-inflammatory studied were also performed (activation of NLRP3 inflammasome; expression of peroxisome proliferator-activated receptor-α; mTORC1 Fox01/3a; transcriptional activation of p65/NF-κB and secretion of cytokines involved in cardiotoxicity (Interleukins 1β, 8, 6). Results Palmitoylethanolamide combined to polydatin co-incubated with doxorubicin exerts vasculoprotective effects, enhancing cell viability of 54.7–68.3% compared to untreated cells (P < 0.001 for all). The formulation reduced significantly the cardiotoxicity through peroxisome proliferator-activated receptor-α–related pathways and NLRP3 inflammasome but without the involvement of calcium homeostasis. Conclusion The present study demonstrates that palmitoylethanolamide and polydatin protects against vasculotoxicity of doxorubicin and trastuzumab by promoting an anti-inflammatory phenotype, representing a new therapeutic approach to resolve doxorubicin-induced vasculotoxicity and inflammation.

Download Full-text

Thykamine Extracts from Spinach Reduce Acute Inflammation In Vivo and Downregulate Phlogogenic Functions of Human Blood Neutrophils In Vitro

Biomedicines ◽

10.3390/biomedicines8070219 ◽

2020 ◽

Vol 8 (7) ◽

pp. 219

Author(s):

Vickie Beaupré ◽

Nathalie Boucher ◽

Isabel Desgagné-Penix

Keyword(s):

In Vitro Models ◽

No Production ◽

Chlorophyll Pigments ◽

Cellular Models ◽

Blood Neutrophils ◽

Anti Inflammatory ◽

Botanical Extract

The anti-inflammatory and antioxidant role of Thykamine, a botanical extract of thylakoides obtained from spinach leaves, has been investigated in animal and cellular models. The oxidative properties have been proven by inhibiting NO production (>98%) in J774A.1 cells and by protecting a linoelic acid emulsion subjected to lipid peroxidation caused by AAPH. Thykamine injected intraperitoneally to rats reduced the inflammatory process of (TNBS)-induced colitis and carrageenan-induced paw edema. As neutrophils are the first cells to migrate to inflammatory sites, the influence of Thykamine on the primary neutrophil functions were studied. Thykamine dose-dependent reduced neutrophil chemiotaxis, phagocytosis, and degranulation. No change in the release of LDH by neutrophils on Thykamine was recorded. Thykamine inhibited by 85% the neutrophil production of O2−. A superoxide recovery activity was observed on a zymography demonstrating a SOD-like enzyme on Thykamine extracts. Spontaneous fluorescence provided by carotenoid and chlorophyll pigments (488/675 nm) detected Thykamine on the surface, in the cytoplasm (mainly central where Golgi are present) and weakly in the nucleus of neutrophils. The results argue that SOD and pigments found in Thykamine are part of its antioxidant and anti-inflammatory properties shown in in vivo and in vitro models of inflammation.

Download Full-text

Anti-Inflammatory and Protein Tyrosine Phosphatase 1B Inhibitory Metabolites from the Antarctic Marine-Derived Fungal Strain Penicillium glabrum SF-7123

Marine Drugs ◽

10.3390/md18050247 ◽

2020 ◽

Vol 18 (5) ◽

pp. 247

Author(s):

Tran Minh Ha ◽

Dong-Cheol Kim ◽

Jae Hak Sohn ◽

Joung Han Yim ◽

Hyuncheol Oh

Keyword(s):

Nitric Oxide ◽

Tyrosine Phosphatase ◽

Suppressive Effect ◽

Fungal Strain ◽

Mitogen Activated Protein Kinase ◽

Protein Tyrosine ◽

Cellular Models ◽

Ic50 Value ◽

Ic50 Values ◽

Anti Inflammatory

A chemical investigation of the marine-derived fungal strain Penicillium glabrum (SF-7123) revealed a new citromycetin (polyketide) derivative (1) and four known secondary fungal metabolites, i.e, neuchromenin (2), asterric acid (3), myxotrichin C (4), and deoxyfunicone (5). The structures of these metabolites were identified primarily by extensive analysis of their spectroscopic data, including NMR and MS data. Results from the initial screening of anti-inflammatory effects showed that 2, 4, and 5 possessed inhibitory activity against the excessive production of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated BV2 microglial cells, with IC50 values of 2.7 µM, 28.1 µM, and 10.6 µM, respectively. Compounds 2, 4, and 5 also inhibited the excessive production of NO, with IC50 values of 4.7 µM, 41.5 µM, and 40.1 µM, respectively, in LPS-stimulated RAW264.7 macrophage cells. In addition, these compounds inhibited LPS-induced overproduction of prostaglandin E2 in both cellular models. Further investigation of the most active compound (2) revealed that these anti-inflammatory effects were associated with a suppressive effect on the over-expression of inducible nitric oxide synthase and cyclooxygenase-2. Finally, we showed that the anti-inflammatory effects of compound 2 were mediated via the downregulation of inflammation-related pathways such as those dependent on nuclear factor kappa B and p38 mitogen-activated protein kinase in LPS-stimulated BV2 and RAW264.7 cells. In the evaluation of the inhibitory effects of the isolated compounds on protein tyrosine phosphate 1B (PTP1B) activity, compound 4 was identified as a noncompetitive inhibitor of PTP1B, with an IC50 value of 19.2 µM, and compound 5 was shown to inhibit the activity of PTP1B, with an IC50 value of 24.3 µM, by binding to the active site of the enzyme. Taken together, this study demonstrates the potential value of marine-derived fungal isolates as a bioresource for bioactive compounds.

Download Full-text

Anti-inflammatory properties of a proprietary bromelain extract (Bromeyal™) after in vitro simulated gastrointestinal digestion

International Journal of Immunopathology and Pharmacology ◽

10.1177/20587384211034686 ◽

2021 ◽

Vol 35 ◽

pp. 205873842110346

Author(s):

Roberta Bottega ◽

Ilaria Persico ◽

Francesco De Seta ◽

Federico Romano ◽

Giovanni Di Lorenzo

Keyword(s):

Complex Mixture ◽

In Vivo Studies ◽

Published Data ◽

Gastrointestinal Digestion ◽

Efficient Treatment ◽

Cellular Models ◽

Bowel Diseases ◽

Anti Inflammatory

Introduction Bromelain is a complex mixture of thiol proteases and other non-proteolytic constituents, commercially extracted primarily from the pineapple stem. Evidence from several in vitro and in vivo studies highlights its excellent bioavailability, lack of side effects, and broad spectrum of medical efficacies, of which the antiphlogistic properties are among the most valuable ones. Bromelain has indeed been employed for the efficient treatment of many inflammatory disorders, ranging from osteoarthritis and inflammatory bowel diseases to cancer-related inflammation. Methods The aim of the current study was to assess the anti-inflammatory effects of bromelain after gastrointestinal digestion simulated in vitro using stomach, intestinal, and chondrocyte human cellular models (AGS, Caco-2, and SW1353, respectively). Results We successfully demonstrated the capability of bromelain to reduce an inflammatory stimulus by reproducing its exposure to the gastro-enteric environment in vitro and assaying its effect in human cell lines derived from stomach, intestinal, and chondrocytes. Conclusion Consistently with the previously published data, our work underpins the relevance of bromelain in the development of safer and more effective anti-inflammatory therapies.

Download Full-text