scholarly journals 5-Aminoisoquinolinone, a PARP-1 Inhibitor, Ameliorates Immune Abnormalities through Upregulation of Anti-Inflammatory and Downregulation of Inflammatory Parameters in T Cells of BTBR Mouse Model of Autism

2021 ◽  
Vol 11 (2) ◽  
pp. 249
Author(s):  
Khaled Alhosaini ◽  
Mushtaq A. Ansari ◽  
Ahmed Nadeem ◽  
Saleh A. Bakheet ◽  
Sabry M. Attia ◽  
...  
Keyword(s):  
T Cells ◽  
Autism Spectrum ◽  
Therapeutic Effects ◽  
Inflammatory Parameters ◽  
Patterns Of Behavior ◽  
Mrna And Protein Expression ◽  
Reciprocal Social Interaction ◽  
Anti Inflammatory ◽  
The Brain ◽  
Parp 1

Autism spectrum disorder (ASD) covers a range of neurodevelopmental disorders involving impairments in communication and repetitive and stereotyped patterns of behavior and reciprocal social interaction. 5-Aminoisoquinolinone (5-AIQ), a PARP-1 inhibitor, has neuroprotective and anti-inflammatory effects. We investigated the influence of 5-AIQ-treatment in BTBR T+ Itpr3tf/J (BTBR) mice as an autism model and used flow cytometry to assess the effect of 5-AIQ on FOXP3, Helios, GATA3, IL-9, IL-10 and IL-17A production by CXCR6+ and CD4+ T cells in the spleen. We also confirmed the effect of 5-AIQ treatment on expression of FOXP3, Helios, GATA3, IL-17A, IL-10, and IL-9 mRNA and protein expression levels in the brain tissue by quantitative PCR and western blotting. Our results demonstrated that 5-AIQ-treated BTBR mice had significantly increased numbers of CXCR6+FOXP3+, CXCR6+IL-10+, and CXCR6+Helios+ cells and decreased numbers of CD4+GATA3+, CD4+IL-9+, and CD4+IL-17A+ cells as compared with those in untreated BTBR mice. Our results further demonstrated that treatment with 5-AIQ in BTBR mice increased expression for FOXP3, IL-10, and Helios, and decreased expression for GATA3, IL-17A, and IL-9 mRNA. Our findings support the hypotheses that 5-AIQ has promising novel therapeutic effects on neuroimmune dysfunction in autism and is associated with modulation of Treg and Th17 cells.

scholarly journals Bergamot Polyphenols Boost Therapeutic Effects of the Diet on Non-Alcoholic Steatohepatitis (NASH) Induced by “Junk Food”: Evidence for Anti-Inflammatory Activity

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1604 ◽  
Author(s):  
Maddalena Parafati ◽  
Antonella Lascala ◽  
Daniele La Russa ◽  
Chiara Mignogna ◽  
Francesca Trimboli ◽  
...  
Keyword(s):  
Weight Loss ◽  
Dietary Intervention ◽  
Inflammatory Activity ◽  
Lipid Lowering ◽  
Therapeutic Effects ◽  
Junk Food ◽  
Alcoholic Fatty Liver ◽  
Inflammatory Parameters ◽  
Hepatic Fat ◽  
Anti Inflammatory

Wrong alimentary behaviors and so-called “junk food” are a driving force for the rising incidence of non-alcoholic fatty liver disease (NAFLD) among children and adults. The “junk food” toxicity can be studied in “cafeteria” (CAF) diet animal model. Young rats exposed to CAF diet become obese and rapidly develop NAFLD. We have previously showed that bergamot (Citrus bergamia Risso et Poiteau) flavonoids, in the form of bergamot polyphenol fraction (BPF), effectively prevent CAF diet-induced NAFLD in rats. Here, we addressed if BPF can accelerate therapeutic effects of weight loss induced by a normocaloric standard chow (SC) diet. 21 rats fed with CAF diet for 16 weeks to induce NAFLD with inflammatory features (NASH) were divided into three groups. Two groups were switched to SC diet supplemented or not with BPF (CAF/SC±BPF), while one group continued with CAF diet (CAF/CAF) for 10 weeks. BPF had no effect on SC diet-induced weight loss, but it accelerated hepatic lipid droplets clearance and reduced blood triglycerides. Accordingly, BPF improved insulin sensitivity, but had little effect on leptin levels. Interestingly, the inflammatory parameters were still elevated in CAF/SC livers compared to CAF/CAF group after 10 weeks of dietary intervention, despite over 90% hepatic fat reduction. In contrast, BPF supplementation decreased hepatic inflammation by reducing interleukin 6 (Il6) mRNA expression and increasing anti-inflammatory Il10, which correlated with fewer Kupffer cells and lower inflammatory foci score in CAF/SC+BPF livers compared to CAF/SC group. These data indicate that BPF mediates a specific anti-inflammatory activity in livers recovering from NASH, while it boosts lipid-lowering and anti-diabetic effects of the dietary intervention.

scholarly journals Preconditioning Enhances the Therapeutic Effects of Mesenchymal Stem Cells on Colitis Through PGE2-Mediated T-Cell Modulation

2018 ◽  
Vol 27 (9) ◽  
pp. 1352-1367 ◽  
Author(s):  
Fu Yuan Yang ◽  
Rui Chen ◽  
Xiaohu Zhang ◽  
Biao Huang ◽  
Lai Ling Tsang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Therapeutic Effect ◽  
T Cell Activation ◽  
Activity Index ◽  
Intraperitoneal Administration ◽  
The Body ◽  
Human Umbilical Cord ◽  
Therapeutic Effects ◽  
Anti Inflammatory

Mesenchymal stem cell (MSC)-based cell therapy has been demonstrated as a promising strategy in the treatment of inflammatory bowel disease (IBD), which is considered an immune disease. While the exact mechanisms underlying the therapeutic effect of MSCs are still unclear, MSCs display anti-inflammatory and immunomodulatory effects by interacting with various immunoregulatory cells. Our previous studies have shown that MSCs can be preconditioned and deconditioned with enhanced cell survival, differentiation and migration. In this study, we evaluated the effect of preconditioning on the immunoregulatory function of human umbilical cord-derived MSCs (hUCMSCs) and their therapeutic effect on treating IBD. Our results show that intraperitoneal administration of deconditioned hUCMSCs (De-hUCMSCs) reduces the disease activity index (DAI), histological colitis score and destruction of the epithelial barrier, and increases the body weight recovery more intensively than that of un-manipulated hUCMSCs. In addition, De-hUCMSCs but not hUCMSCs elicit anti-apoptotic effects via induction of the ERK pathway during the early stage of IBD development. In vitro co-culture studies indicate that De-hUCMSCs suppress T-cell proliferation and activation more markedly than hUCMSCs. Moreover, De-hUCMSCs block the induction of inflammatory cytokines such as tumor necrosis factor (TNF)α and interleukin (IL)-2, while promoting the secretion of the anti-inflammatory cytokine IL-10 in T-cells. Mechanically, we find that prostaglandin E2 (PGE2) secretion is significantly increased in De-hUCMSCs, the suppression of which dramatically abrogates the inhibitory effect of De-hUCMSCs on T-cell activation, implying that the crosstalk between De-hUCMSCs and T-cells is mediated by PGE2. Together, we have demonstrated that preconditioning enhances the immunosuppressive and therapeutic effects of hUCMSCs on treating IBD via increased secretion of PGE2.

scholarly journals (-)-Oleocanthal Nutraceuticals for Alzheimer’s Disease Amyloid Pathology: Novel Oral Formulations, Therapeutic, and Molecular Insights in 5xFAD Transgenic Mice Model

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1702
Author(s):  
Afsana Tajmim ◽  
Areli K. Cuevas-Ocampo ◽  
Abu Bakar Siddique ◽  
Mohammed H. Qusa ◽  
Judy Ann King ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Virgin Olive Oil ◽  
Therapeutic Effects ◽  
Dissolution Profile ◽  
Amyloid Pathology ◽  
Oral Formulations ◽  
Aβ Amyloid ◽  
Anti Inflammatory ◽  
The Brain

Alzheimer’s disease (AD) is a complex progressive neurodegenerative disorder affecting humans mainly through the deposition of Aβ-amyloid (Aβ) fibrils and accumulation of neurofibrillary tangles in the brain. Currently available AD treatments only exhibit symptomatic relief but do not generally intervene with the amyloid and tau pathologies. The extra-virgin olive oil (EVOO) monophenolic secoiridoid S-(–)-oleocanthal (OC) showed anti-inflammatory activity through COX system inhibition with potency comparable to the standard non-steroidal anti-inflammatory drug (NSAID) like ibuprofen. OC also showed positive in vitro, in vivo, and clinical therapeutic effects against cardiovascular diseases, many malignancies, and AD. Due to its pungent, astringent, and irritant taste, OC should be formulated in acceptable dosage form before its oral use as a potential nutraceutical. The objective of this study is to develop new OC oral formulations, assess whether they maintained OC activity on the attenuation of β-amyloid pathology in a 5xFAD mouse model upon 4-month oral dosing use. Exploration of potential OC formulations underlying molecular mechanism is also within this study scope. OC powder formulation (OC-PF) and OC-solid dispersion formulation with erythritol (OC-SD) were prepared and characterized using FT-IR spectroscopy, powder X-ray diffraction, and scanning electron microscopy (SEM) analyses. Both formulations showed an improved OC dissolution profile. OC-PF and OC-SD improved memory deficits of 5xFAD mice in behavioral studies. OC-PF and OC-SD exhibited significant attenuation of the accumulation of Aβ plaques and tau phosphorylation in the brain of 5xFAD female mice. Both formulations markedly suppressed C3AR1 (complement component 3a receptor 1) activity by targeting the downstream marker STAT3. Collectively, these results demonstrate the potential for the application of OC-PF as a prospective nutraceutical or dietary supplement to control the progression of amyloid pathogenesis associated with AD.

scholarly journals Oxidative Stress and Neuroinflammation as a Pivot in Drug Abuse. A Focus on the Therapeutic Potential of Antioxidant and Anti-Inflammatory Agents and Biomolecules

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 830
Author(s):  
Pablo Berríos-Cárcamo ◽  
Mauricio Quezada ◽  
María Elena Quintanilla ◽  
Paola Morales ◽  
Marcelo Ezquer ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Drug Abuse ◽  
Drugs Of Abuse ◽  
Therapeutic Potential ◽  
Drug Consumption ◽  
Therapeutic Effects ◽  
Drug Craving ◽  
Brain Oxidative Stress ◽  
Anti Inflammatory ◽  
The Brain

Drug abuse is a major global health and economic problem. However, there are no pharmacological treatments to effectively reduce the compulsive use of most drugs of abuse. Despite exerting different mechanisms of action, all drugs of abuse promote the activation of the brain reward system, with lasting neurobiological consequences that potentiate subsequent consumption. Recent evidence shows that the brain displays marked oxidative stress and neuroinflammation following chronic drug consumption. Brain oxidative stress and neuroinflammation disrupt glutamate homeostasis by impairing synaptic and extra-synaptic glutamate transport, reducing GLT-1, and system Xc− activities respectively, which increases glutamatergic neurotransmission. This effect consolidates the relapse-promoting effect of drug-related cues, thus sustaining drug craving and subsequent drug consumption. Recently, promising results as experimental treatments to reduce drug consumption and relapse have been shown by (i) antioxidant and anti-inflammatory synthetic molecules whose effects reach the brain; (ii) natural biomolecules secreted by mesenchymal stem cells that excel in antioxidant and anti-inflammatory properties, delivered via non-invasive intranasal administration to animal models of drug abuse and (iii) potent anti-inflammatory microRNAs and anti-miRNAs which target the microglia and reduce neuroinflammation and drug craving. In this review, we address the neurobiological consequences of brain oxidative stress and neuroinflammation that follow the chronic consumption of most drugs of abuse, and the current and potential therapeutic effects of antioxidants and anti-inflammatory agents and biomolecules to reduce these drug-induced alterations and to prevent relapse.

scholarly journals Potential Therapeutic Effects of New Ruthenium (III) Complex with Quercetin: Characterization, Structure, Gene Regulation, and Antitumor and Anti-Inflammatory Studies (RuIII/Q Novel Complex Is a Potent Immunoprotective Agent)

Crystals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 367
Author(s):  
Moamen S. Refat ◽  
Reham Z. Hamza ◽  
Abdel Majid A. Adam ◽  
Hosam A. Saad ◽  
Adil A. Gobouri ◽  
...  
Keyword(s):  
Reproductive Toxicity ◽  
Average Diameter ◽  
Testicular Tissue ◽  
Male Rats ◽  
Flavonoid Compound ◽  
Therapeutic Effects ◽  
Ultrastructural Studies ◽  
Ameliorative Effect ◽  
Anti Inflammatory ◽  
The Brain

The aim of this study was to evaluate the antioxidant and anti-inflammatory effects of the new [Ru(Q)(Cl)2(H2O)2] complex (RuIII/Q). A new vital complex containing quercetin flavonoid compound (Q) with ruthenium (III) ions was synthesized. The molar conductivity of the RuIII/Q complex was measured in dimethylsulfoxide (DMSO) with value 12 (Ω−1 mol−1 cm−1, indicating their non-electrolytic nature. Infrared (FTIR) spectroscopic investigation of the RuIII/Q complex indicated that Q is coordinated as a bidentate with Ru metal ions through the oxygen of carbonyl C(4)=O group and oxygen of phenolic C(3)−O group based on the wavenumber shifts at 1654 and 1335 cm−1 respectively. The electronic (UV−Vis) spectra and the magnetic susceptibility value (1.85 B.M.) revealed that the Ru(III) complex has an octahedral geometry. The average diameter of the RuIII/Q nanoparticles was approximately 7–15 nm according to the transmission electron microscopy. The thermogravimetric study (TG/DTG) indicates that the RuIII/Q compound is quite stable until 300 °C. To assess biological activity, 60 male rats were allocated to six groups, namely control, DG (D-galactose), Q, RuIII/Q, DG plus Q, and DG plus RuIII/Q. Antioxidant enzymes (SOD, CAT, GPx, and GRx), markers of lipid peroxidation (such as MDA), expression of genes (namely Nrf2, Cu-ZnSOD, CAT, GPx, cyto c, P53, Bax, BCl2, caspase-3, and caspase-9 in testicular tissue), glutamate, 4-hydroxynonenal (HNE), GSH, HCY, amyloid beta, and GABA levels were evaluated in brain tissues. Cytokines, such as IL-6 and TNF-α, histological and ultrastructural studies were estimated in both the brain and testicular tissues, while the comet assay was performed in the brain tissue. RuIII/Q administration either alone or combined with DG reduced oxidative injury to normal levels and decreased apoptotic activities. Thus, RuIII/Q inhibited injury in both the testis and brain and reduced oxidative stress in male rats. The (RuIII/Q) complex has a potent ameliorative effect against aging neurotoxicity, reproductive toxicity, and antihepatic cancer activity induced by D-galactose (DG).

Anti-Inflammatory Properties of Plant Derived Natural Products – A Systematic Review

2019 ◽  
Vol 26 (24) ◽  
pp. 4506-4536 ◽  
Author(s):  
Iris E. Allijn ◽  
René P. Brinkhuis ◽  
Gert Storm ◽  
Raymond M. Schiffelers
Keyword(s):  
Systematic Review ◽  
Natural Products ◽  
Positive Control ◽  
Therapeutic Effects ◽  
Reference Compound ◽  
Individual Molecular Species ◽  
The Past ◽  
Anti Inflammatory ◽  
The Individual ◽  
Natural Medicines

Traditionally, natural medicines have been administered as plant extracts, which are composed of a mixture of molecules. The individual molecular species in this mixture may or may not contribute to the overall medicinal effects and some may even oppose the beneficial activity of others. To better control therapeutic effects, studies that characterized specific molecules and describe their individual activity that have been performed over the past decades. These studies appear to underline that natural products are particularly effective as antioxidants and anti-inflammatory agents. In this systematic review we aimed to identify potent anti-inflammatory natural products and relate their efficacy to their chemical structure and physicochemical properties. To identify these compounds, we performed a comprehensive literature search to find those studies, in which a dose-response description and a positive control reference compound was used to benchmark the observed activity. Of the analyzed papers, 7% of initially selected studies met these requirements and were subjected to further analysis. This analysis revealed that most selected natural products indeed appeared to possess anti-inflammatory activities, in particular anti-oxidative properties. In addition, 14% of the natural products outperformed the remaining natural products in all tested assays and are attractive candidates as new anti-inflammatory agents.

Role of Resveratrol in Modulating microRNAs in Human Diseases: From Cancer to Inflammatory Disorder

2020 ◽  
Vol 28 (2) ◽  
pp. 360-376 ◽  
Author(s):  
Atefeh Amiri ◽  
Maryam Mahjoubin-Tehran ◽  
Zatollah Asemi ◽  
Alimohammad Shafiee ◽  
Sarah Hajighadimi ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Antioxidant Activities ◽  
Natural Compounds ◽  
Therapeutic Effects ◽  
Inflammatory Disorder ◽  
Inflammatory Disorders ◽  
Therapeutic Modalities ◽  
Anti Cancer ◽  
Current Therapies ◽  
Anti Inflammatory

: Cancer and inflammatory disorders are two important public health issues worldwide with significant socio.economic impacts. Despite several efforts, the current therapeutic platforms are associated with severe limitations. Therefore, developing new therapeutic strategies for the treatment of these diseases is a top priority. Besides current therapies, the utilization of natural compounds has emerged as a new horizon for the treatment of cancer and inflammatory disorders as well. Such natural compounds could be used either alone or in combination with the standard cancer therapeutic modalities such as chemotherapy, radiotherapy, and immunotherapy. Resveratrol is a polyphenolic compound that is found in grapes as well as other foods. It has been found that this medicinal agent displays a wide pharmacological spectrum, including anti-cancer, anti-inflammatory, anti-microbial, and antioxidant activities. Recently, clinical and pre-clinical studies have highlighted the anti-cancer and anti-inflammatory effects of resveratrol. Increasing evidence revealed that resveratrol exerts its therapeutic effects by targeting various cellular and molecular mechanisms. Among cellular and molecular targets that are modulated by resveratrol, microRNAs (miRNAs) have appeared as key targets. MiRNAs are short non-coding RNAs that act as epigenetic regulators. These molecules are involved in many processes that are involved in the initiation and progression of cancer and inflammatory disorders. Herein, we summarized various miRNAs that are directly/indirectly influenced by resveratrol in cancer and inflammatory disorders.

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