Recent Advances on the Anti-Inflammatory and Antioxidant Properties of Red Grape Polyphenols: In Vitro and In Vivo Studies

In this review, special emphasis will be placed on red grape polyphenols for their antioxidant and anti-inflammatory activities. Therefore, their capacity to inhibit major pathways responsible for activation of oxidative systems and expression and release of proinflammatory cytokines and chemokines will be discussed. Furthermore, regulation of immune cells by polyphenols will be illustrated with special reference to the activation of T regulatory cells which support a tolerogenic pathway at intestinal level. Additionally, the effects of red grape polyphenols will be analyzed in obesity, as a low-grade systemic inflammation. Also, possible modifications of inflammatory bowel disease biomarkers and clinical course have been studied upon polyphenol administration, either in animal models or in clinical trials. Moreover, the ability of polyphenols to cross the blood–brain barrier has been exploited to investigate their neuroprotective properties. In cancer, polyphenols seem to exert several beneficial effects, even if conflicting data are reported about their influence on T regulatory cells. Finally, the effects of polyphenols have been evaluated in experimental models of allergy and autoimmune diseases. Conclusively, red grape polyphenols are endowed with a great antioxidant and anti-inflammatory potential but some issues, such as polyphenol bioavailability, activity of metabolites, and interaction with microbiota, deserve deeper studies.

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Recent Advances on the Anti-inflammatory and Anti-oxidant properties of Red Grape Polyphenols: In Vitro and in Vivo Studies

10.20944/preprints201912.0030.v1 ◽

2019 ◽

Author(s):

Thea Magrone ◽

Manrico Magrone ◽

Matteo Antonio Russo ◽

Emilio Jirillo

Keyword(s):

T Regulatory Cells ◽

In Vivo Studies ◽

Low Grade ◽

Regulatory Cells ◽

Grape Polyphenols ◽

Anti Oxidant ◽

Anti Inflammatory ◽

Red Grape

In this review, special emphasis will be placed on red grape polyphenols for their anti-oxidant and anti-inflammatory activities. Therefore, their capacity to inhibit major pathways responsible for activation of oxidative systems and expression and release of pro-inflammatory cytokines and chemokines will be discussed. Furthermore, regulation of immune cells by polyphenols will be illustrated with special reference to the activation of T regulatory cells which support a tolerogenic pathway at intestinal level. Furthermore, the effects of red grape polyphenols will be analyzed in obesity, as a low grade systemic inflammation. Also, possible modifications of inflammatory bowel disease biomarkers and clinical course have been studied upon polyphenol administration, either in animal models or in clinical trials. Moreover, the ability of polyphenols to cross the blood-brain barrier has been exploited to investigate their neuroprotective properties. In cancer, polyphenols seem to exert several beneficial effects, even if conflicting data are reported about their influence on T regulatory cells. Finally, the effects of polyphenols have been evaluated in experimental models of allergy and autoimmune diseases. Conclusively, red grape polyphenols are endowed with a great anti-oxidant and anti-inflammatory potential but some issues, such as polyphenol bioavailability, activity of metabolites and interaction with microbiota, deserve deeper studies.

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The Role of Nutraceuticals in Osteoarthritis Prevention and Treatment: Focus on n-3 PUFAs

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/4878562 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Francesca Oppedisano ◽

Rosa Maria Bulotta ◽

Jessica Maiuolo ◽

Micaela Gliozzi ◽

Vincenzo Musolino ◽

...

Keyword(s):

Joint Destruction ◽

Antioxidant Properties ◽

Cartilage Destruction ◽

In Vivo Studies ◽

Ros Generation ◽

Pathophysiological Mechanisms ◽

Prevention And Treatment ◽

Anti Inflammatory

Osteoarthritis (OA) is a disease caused by joint degeneration with massive cartilage loss, and obesity is among the risk factors for its onset, though the pathophysiological mechanisms underlying the disease and better therapeutic approach still remain to be assessed. In recent years, several nutraceutical interventions have been investigated in order to define better solutions for preventing and treating OA. Among them, polyunsaturated fatty acids (n-3 PUFAs) appear to represent potential candidates in counteracting OA and its consequences, due to their anti-inflammatory, antioxidant, and chondroinductive effects. PUFAs have been found to counteract the onset and progression of OA by reducing bone and cartilage destruction, inhibiting proinflammatory cytokine release, reactive oxygen species (ROS) generation, and the NF-κB pathway’s activation. Moreover, a diet rich in n-3 PUFAs and their derivatives (maresins and resolvins) demonstrates beneficial effects on associated pain reduction. Finally, it has been shown that together with the anti-inflammatory and antioxidant properties of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, their antiapoptotic and antiangiogenic effects contribute in reducing OA development. The present review is aimed at assessing evidence suggesting the potential benefit of nutraceutical supplementation with PUFAs in OA management according to their efficacy in targeting relevant pathophysiological mechanisms responsible for inflammation and joint destruction processes, and this may represent a novel and potentially useful approach in OA prevention and treatment. For that purpose, a PubMed literature survey was conducted with a focus on some in vitro and in vivo studies and clinical trials from 2015 to 2020.

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A bispecific antibody agonist of the IL-2 heterodimeric receptor preferentially promotes in vivo expansion of CD8 and NK cells

Scientific Reports ◽

10.1038/s41598-021-90096-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Katherine E. Harris ◽

Kyle J. Lorentsen ◽

Harbani K. Malik-Chaudhry ◽

Kaitlyn Loughlin ◽

Harish Medlari Basappa ◽

...

Keyword(s):

T Cells ◽

Nk Cells ◽

Bispecific Antibody ◽

T Regulatory Cells ◽

Tumor Regression ◽

Interleukin 2 ◽

In Vivo Studies ◽

Preferential Binding

AbstractThe use of recombinant interleukin-2 (IL-2) as a therapeutic protein has been limited by significant toxicities despite its demonstrated ability to induce durable tumor-regression in cancer patients. The adverse events and limited efficacy of IL-2 treatment are due to the preferential binding of IL-2 to cells that express the high-affinity, trimeric receptor, IL-2Rαβγ such as endothelial cells and T-regulatory cells, respectively. Here, we describe a novel bispecific heavy-chain only antibody which binds to and activates signaling through the heterodimeric IL-2Rβγ receptor complex that is expressed on resting T-cells and NK cells. By avoiding binding to IL-2Rα, this molecule circumvents the preferential T-reg activation of native IL-2, while maintaining the robust stimulatory effects on T-cells and NK-cells in vitro. In vivo studies in both mice and cynomolgus monkeys confirm the molecule’s in vivo biological activity, extended pharmacodynamics due to the Fc portion of the molecule, and enhanced safety profile. Together, these results demonstrate that the bispecific antibody is a safe and effective IL-2R agonist that harnesses the benefits of the IL-2 signaling pathway as a potential anti-cancer therapy.

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The Immunomodulatory Effects of Honey and Associated Flavonoids in Cancer

Nutrients ◽

10.3390/nu13041269 ◽

2021 ◽

Vol 13 (4) ◽

pp. 1269

Author(s):

Razan J. Masad ◽

Shoja M. Haneefa ◽

Yassir A. Mohamed ◽

Ashraf Al-Sbiei ◽

Ghada Bashir ◽

...

Keyword(s):

Immune Responses ◽

Antioxidant Properties ◽

In Vivo Studies ◽

Immunomodulatory Effects ◽

Bioactive Constituents ◽

Cancer Cell Growth ◽

Cancer Types ◽

Immunomodulatory Properties

Honey has exerted a high impact in the field of alternative medicine over many centuries. In addition to its wound healing, anti-microbial and antioxidant properties, several lines of evidence have highlighted the efficiency of honey and associated bioactive constituents as anti-tumor agents against a range of cancer types. Mechanistically, honey was shown to inhibit cancer cell growth through its pro-apoptotic, anti-proliferative and anti-metastatic effects. However, the potential of honey to regulate anti-tumor immune responses is relatively unexplored. A small number of in vitro and in vivo studies have demonstrated the ability of honey to modulate the immune system by inducing immunostimulatory as well as anti-inflammatory effects. In the present review, we summarize the findings from different studies that aimed to investigate the immunomodulatory properties of honey and its flavonoid components in relation to cancer. While these studies provide promising data, additional research is needed to further elucidate the immunomodulatory properties of honey, and to enable its utilization as an adjuvant therapy in cancer.

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Efficacy of Posidonia oceanica Extract against Inflammatory Pain: In Vivo Studies in Mice

Marine Drugs ◽

10.3390/md19020048 ◽

2021 ◽

Vol 19 (2) ◽

pp. 48

Author(s):

Laura Micheli ◽

Marzia Vasarri ◽

Emanuela Barletta ◽

Elena Lucarini ◽

Carla Ghelardini ◽

...

Keyword(s):

Inflammatory Pain ◽

Ex Vivo ◽

Antioxidant Properties ◽

Posidonia Oceanica ◽

In Vivo Studies ◽

Myeloperoxidase Activity ◽

Intraplantar Injection ◽

Hot Plate Test ◽

Anti Inflammatory

Posidonia oceanica (L.) Delile is traditionally used for its beneficial properties. Recently, promising antioxidant and anti-inflammatory biological properties emerged through studying the in vitro activity of the ethanolic leaves extract (POE). The present study aims to investigate the anti-inflammatory and analgesic role of POE in mice. Inflammatory pain was modeled in CD-1 mice by the intraplantar injection of carrageenan, interleukin IL-1β and formalin. Pain threshold was measured by von Frey and paw pressure tests. Nociceptive pain was studied by the hot-plate test. POE (10–100 mg kg−1) was administered per os. The paw soft tissue of carrageenan-treated animals was analyzed to measure anti-inflammatory and antioxidant effects. POE exerted a dose-dependent, acute anti-inflammatory effect able to counteract carrageenan-induced pain and paw oedema. Similar anti-hyperalgesic and anti-allodynic results were obtained when inflammation was induced by IL-1β. In the formalin test, the pre-treatment with POE significantly reduced the nocifensive behavior. Moreover, POE was able to evoke an analgesic effect in naïve animals. Ex vivo, POE reduced the myeloperoxidase activity as well as TNF-α and IL-1β levels; further antioxidant properties were highlighted as a reduction in NO concentration. POE is the candidate for a new valid strategy against inflammation and pain.

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In Vitro Evaluation of the Anti-Inflammatory Effect of KMUP-1 and in Vivo Analysis of Its Therapeutic Potential in Osteoarthritis

Biomedicines ◽

10.3390/biomedicines9060615 ◽

2021 ◽

Vol 9 (6) ◽

pp. 615

Author(s):

Shang-En Huang ◽

Erna Sulistyowati ◽

Yu-Ying Chao ◽

Bin-Nan Wu ◽

Zen-Kong Dai ◽

...

Keyword(s):

Articular Cartilage ◽

Inflammatory Responses ◽

Therapeutic Potential ◽

Antioxidant Properties ◽

Serum Levels ◽

Gene Expressions ◽

Tnf Α ◽

Anti Inflammatory

Osteoarthritis is a degenerative arthropathy that is mainly characterized by dysregulation of inflammatory responses. KMUP-1, a derived chemical synthetic of xanthine, has been shown to have anti-inflammatory and antioxidant properties. Here, we aimed to investigate the in vitro anti-inflammatory and in vivo anti-osteoarthritis effects of KMUP-1. Protein and gene expressions of inflammation markers were determined by ELISA, Western blotting and microarray, respectively. RAW264.7 mouse macrophages were cultured and pretreated with KMUP-1 (1, 5, 10 μM). The productions of TNF-α, IL-6, MMP-2 and MMP- 9 were reduced by KMUP-1 pretreatment in LPS-induced inflammation of RAW264.7 cells. The expressions of iNOS, TNF-α, COX-2, MMP-2 and MMP-9 were also inhibited by KMUP-1 pretreatment. The gene expression levels of TNF and COX families were also downregulated. In addition, KMUP-1 suppressed the activations of ERK, JNK and p38 as well as phosphorylation of IκBα/NF-κB signaling pathways. Furthermore, SIRT1 inhibitor attenuated the inhibitory effect of KMUP-1 in LPS-induced NF-κB activation. In vivo study showed that KMUP-1 reduced mechanical hyperalgesia in monoiodoacetic acid (MIA)-induced rats OA. Additionally, KMUP-1 pretreatment reduced the serum levels of TNF-α and IL-6 in MIA-injected rats. Moreover, macroscopic and histological observation showed that KMUP-1 reduced articular cartilage erosion in rats. Our results demonstrated that KMUP-1 inhibited the inflammatory responses and restored SIRT1 in vitro, alleviated joint-related pain and cartilage destruction in vivo. Taken together, KMUP-1 has the potential to improve MIA-induced articular cartilage degradation by inhibiting the levels and expression of inflammatory mediators suggesting that KMUP-1 might be a potential therapeutic agent for OA.

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Histone/protein deacetylases and T-cell immune responses

Blood ◽

10.1182/blood-2011-10-292003 ◽

2012 ◽

Vol 119 (11) ◽

pp. 2443-2451 ◽

Cited By ~ 85

Author(s):

Tatiana Akimova ◽

Ulf H. Beier ◽

Yujie Liu ◽

Liqing Wang ◽

Wayne W. Hancock

Keyword(s):

T Cell ◽

Cell Biology ◽

T Regulatory Cells ◽

Hdac Inhibitors ◽

Experimental Studies ◽

Cell Subset ◽

Histone Protein ◽

Anti Inflammatory

Abstract Clinical and experimental studies show that inhibition of histone/protein deacetylases (HDAC) can have important anti-neoplastic effects through cytotoxic and proapoptotic mechanisms. There are also increasing data from nononcologic settings that HDAC inhibitors (HDACi) can exhibit useful anti-inflammatory effects in vitro and in vivo, unrelated to cytotoxicity or apoptosis. These effects can be cell-, tissue-, or context-dependent and can involve modulation of specific inflammatory signaling pathways as well as epigenetic mechanisms. We review recent advances in the understanding of how HDACi alter immune and inflammatory processes, with a particular focus on the effects of HDACi on T-cell biology, including the activation and functions of conventional T cells and the unique T-cell subset, composed of Foxp3+ T-regulatory cells. Although studies are still needed to tease out details of the various biologic roles of individual HDAC isoforms and their corresponding selective inhibitors, the anti-inflammatory effects of HDACi are already promising and may lead to new therapeutic avenues in transplantation and autoimmune diseases.

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Mitoprotective Effects of Centella asiatica (L.) Urb.: Anti-Inflammatory and Neuroprotective Opportunities in Neurodegenerative Disease

Frontiers in Pharmacology ◽

10.3389/fphar.2021.687935 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jia Hui Wong ◽

Anna M. Barron ◽

Jafri Malin Abdullah

Keyword(s):

Neurodegenerative Disease ◽

Healthy Aging ◽

Brain Aging ◽

Antioxidant Properties ◽

Centella Asiatica ◽

Asiatic Acid ◽

Wide Range ◽

Anti Inflammatory

Natural products remain a crucial source of drug discovery for accessible and affordable solutions for healthy aging. Centella asiatica (L.) Urb. (CA) is an important medicinal plant with a wide range of ethnomedicinal uses. Past in vivo and in vitro studies have shown that the plant extract and its key components, such as asiatic acid, asiaticoside, madecassic acid and madecassoside, exhibit a range of anti-inflammatory, neuroprotective, and cognitive benefits mechanistically linked to mitoprotective and antioxidant properties of the plant. Mitochondrial dysfunction and oxidative stress are key drivers of aging and neurodegenerative disease, including Alzheimer’s disease and Parkinson’s disease. Here we appraise the growing body of evidence that the mitoprotective and antioxidative effects of CA may potentially be harnessed for the treatment of brain aging and neurodegenerative disease.

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Anti-Inflammatory Potential of Daturaolone from Datura innoxia Mill.: In Silico, In Vitro and In Vivo Studies

Pharmaceuticals ◽

10.3390/ph14121248 ◽

2021 ◽

Vol 14 (12) ◽

pp. 1248

Author(s):

Muhammad Waleed Baig ◽

Humaira Fatima ◽

Nosheen Akhtar ◽

Hidayat Hussain ◽

Mohammad K. Okla ◽

...

Keyword(s):

In Silico ◽

Therapeutic Potential ◽

In Vivo Studies ◽

Metabolic Reaction ◽

Datura Innoxia ◽

In Vivo Models ◽

Immobility Time ◽

Anti Inflammatory

Exploration of leads with therapeutic potential in inflammatory disorders is worth pursuing. In line with this, the isolated natural compound daturaolone from Datura innoxia Mill. was evaluated for its anti-inflammatory potential using in silico, in vitro and in vivo models. Daturaolone follows Lipinski’s drug-likeliness rule with a score of 0.33. Absorption, distribution, metabolism, excretion and toxicity prediction show strong plasma protein binding; gastrointestinal absorption (Caco-2 cells permeability = 34.6 nm/s); no blood–brain barrier penetration; CYP1A2, CYP2C19 and CYP3A4 metabolism; a major metabolic reaction, being aliphatic hydroxylation; no hERG inhibition; and non-carcinogenicity. Predicted molecular targets were mainly inflammatory mediators. Molecular docking depicted H-bonding interaction with nuclear factor kappa beta subunit (NF-κB), cyclooxygenase-2, 5-lipoxygenase, phospholipase A2, serotonin transporter, dopamine receptor D1 and 5-hydroxy tryptamine. Its cytotoxicity (IC50) value in normal lymphocytes was >20 µg/mL as compared to cancer cells (Huh7.5; 17.32 ± 1.43 µg/mL). Daturaolone significantly inhibited NF-κB and nitric oxide production with IC50 values of 1.2 ± 0.8 and 4.51 ± 0.92 µg/mL, respectively. It significantly reduced inflammatory paw edema (81.73 ± 3.16%), heat-induced pain (89.47 ± 9.01% antinociception) and stress-induced depression (68 ± 9.22 s immobility time in tail suspension test). This work suggests a possible anti-inflammatory role of daturaolone; however, detailed mechanistic studies are still necessary to corroborate and extrapolate the findings.

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