In Vitro Digested Nut Oils Attenuate the Lipopolysaccharide-Induced Inflammatory Response in Macrophages

Nut consumption is known for its health benefits, in particular in inflammatory diseases. A possible mechanism for these effects could be their beneficial fatty acid composition. Nuts mainly contain mono- and polyunsaturated fatty acids, which have anti-inflammatory properties. However, studies investigating the effects of nut extracts on inflammatory processes on the molecular level are rare. We therefore prepared oily nut extracts after in vitro digestion and saponification of the fat-soluble constituents. Besides chromatographic analysis, cell culture experiments were performed using murine macrophages (RAW264.7) to study the capacity of different nut extracts (hazelnut, almond, walnut, macadamia, and pistachio) to modulate inflammatory processes. Oleic acid was the main fatty acid in hazelnut, almond, macadamia, and pistachio extracts. Both oily nut extracts and pure oleic acid significantly reduced the LPS-induced expression of iNos, Cox2, Tnfα, Il1β, and Il6 mRNAs. iNos protein expression was down-regulated followed by reduced nitric oxide formation. Thus, nut extracts at concentrations achievable in the digestive tract inhibit the expression and formation of inflammatory mediators in macrophages. Hence, a beneficial contribution of nut consumption to inflammatory diseases can be assumed. We are convinced that these results provide new insights on the molecular mechanisms involved in the health-beneficial effects of nuts.

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Assessment of In Vitro Bioaccessibility of Polyphenols from Annurca, Limoncella, Red Delicious, and Golden Delicious Apples Using a Sequential Enzymatic Digestion Model

Antioxidants ◽

10.3390/antiox10040541 ◽

2021 ◽

Vol 10 (4) ◽

pp. 541

Author(s):

Giulia Graziani ◽

Anna Gaspari ◽

Claudio Di Vaio ◽

Aurora Cirillo ◽

Carolina Liana Ronca ◽

...

Keyword(s):

Antioxidant Activity ◽

Antioxidant Activities ◽

In Vitro Digestion ◽

Enzymatic Digestion ◽

Beneficial Effects ◽

Golden Delicious ◽

In Vitro Bioaccessibility ◽

Inflammatory Processes ◽

Great Relevance

Four different varieties of apples have been considered (Limoncella, Annurca, Red Delicious, and Golden Delicious) to estimate the extent of colon polyphenolics release after in vitro sequential enzyme digestion. Since several studies report a positive effect of apple polyphenols in colonic damage, we found of interest to investigate the colon release of polyphenols in different varieties of apples in order to assess their prevention of colonic damage. UHPLC-HRMS analysis and antioxidant activity (ABTS, DPPH, and FRAP assays) were carried out on the apple extracts (peel, flesh, and whole fruit) obtained from not digested samples and on bioaccessible fractions (duodenal and colon bioaccessible fractions) after in vitro digestion. Polyphenolic content and antioxidant activities were found to vary significantly among the tested cultivars with Limoncella showing the highest polyphenol content accompanied by an excellent antioxidant activity in both flesh and whole fruit. The overall trend of soluble antioxidant capacity from the soluble duodenal phase (SDP) and soluble colonic phase (SCP) followed the concentrations of flavanols, procyandinis, and hydroxycinnamic acids under the same digestive steps. Our results highlighted that on average 64.2% of the total soluble antioxidant activity was released in the SCP with Limoncella exhibiting the highest values (82.31, 70.05, and 65.5%, respectively for whole fruit, flesh, and peel). This result suggested that enzymatic treatment with pronase E and viscozyme L, to reproduce biochemical conditions occurring in the colon, is effective for breaking the dietary fiber-polyphenols interactions and for the release of polyphenols which can exercise their beneficial effects in the colon. The beneficial effects related to the Limoncella consumption could thus be of potential great relevance to counteract the adverse effects of pro-oxidant and inflammatory processes on intestinal cells.

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Therapeutic Potential of Volatile Terpenes and Terpenoids from Forests for Inflammatory Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms21062187 ◽

2020 ◽

Vol 21 (6) ◽

pp. 2187 ◽

Cited By ~ 10

Author(s):

Taejoon Kim ◽

Bokyeong Song ◽

Kyoung Sang Cho ◽

Im-Soon Lee

Keyword(s):

Molecular Mechanisms ◽

Therapeutic Potential ◽

Inflammatory Diseases ◽

Biological Activities ◽

Beneficial Effects ◽

Forested Areas ◽

Inflammatory Processes ◽

Respiratory Inflammation ◽

Volatile Terpenes ◽

Anti Inflammatory

Forest trees are a major source of biogenic volatile organic compounds (BVOCs). Terpenes and terpenoids are known as the main BVOCs of forest aerosols. These compounds have been shown to display a broad range of biological activities in various human disease models, thus implying that forest aerosols containing these compounds may be related to beneficial effects of forest bathing. In this review, we surveyed studies analyzing BVOCs and selected the most abundant 23 terpenes and terpenoids emitted in forested areas of the Northern Hemisphere, which were reported to display anti-inflammatory activities. We categorized anti-inflammatory processes related to the functions of these compounds into six groups and summarized their molecular mechanisms of action. Finally, among the major 23 compounds, we examined the therapeutic potentials of 12 compounds known to be effective against respiratory inflammation, atopic dermatitis, arthritis, and neuroinflammation among various inflammatory diseases. In conclusion, the updated studies support the beneficial effects of forest aerosols and propose their potential use as chemopreventive and therapeutic agents for treating various inflammatory diseases.

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Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control

Mediators of Inflammation ◽

10.1155/2016/3094642 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 93

Author(s):

Young-Sun Lee ◽

Hee-Sook Jun

Keyword(s):

Pancreatic Beta Cells ◽

Molecular Mechanisms ◽

Inflammatory Diseases ◽

Glucose Disposal ◽

Dipeptidyl Peptidase 4 ◽

Beneficial Effects ◽

Anti Inflammatory ◽

Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1) is an incretin hormone mainly secreted from intestinal L cells in response to nutrient ingestion. GLP-1 has beneficial effects for glucose homeostasis by stimulating insulin secretion from pancreatic beta-cells, delaying gastric emptying, decreasing plasma glucagon, reducing food intake, and stimulating glucose disposal. Therefore, GLP-1-based therapies such as GLP-1 receptor agonists and inhibitors of dipeptidyl peptidase-4, which is a GLP-1 inactivating enzyme, have been developed for treatment of type 2 diabetes. In addition to glucose-lowering effects, emerging data suggests that GLP-1-based therapies also show anti-inflammatory effects in chronic inflammatory diseases including type 1 and 2 diabetes, atherosclerosis, neurodegenerative disorders, nonalcoholic steatohepatitis, diabetic nephropathy, asthma, and psoriasis. This review outlines the anti-inflammatory actions of GLP-1-based therapies on diseases associated with chronic inflammationin vivoandin vitro, and their molecular mechanisms of anti-inflammatory action.

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Molecular Mechanisms of ZC3H12C/Reg-3 Biological Activity and Its Involvement in Psoriasis Pathology

International Journal of Molecular Sciences ◽

10.3390/ijms22147311 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7311

Author(s):

Mateusz Wawro ◽

Jakub Kochan ◽

Weronika Sowinska ◽

Aleksandra Solecka ◽

Karolina Wawro ◽

...

Keyword(s):

Family Member ◽

Cellular Localization ◽

Molecular Mechanisms ◽

Inflammatory Diseases ◽

Association Studies ◽

Psoriasis Patient ◽

Genome Wide Association Studies ◽

Mrna Levels ◽

Transcript Levels

The members of the ZC3H12/MCPIP/Regnase family of RNases have emerged as important regulators of inflammation. In contrast to Regnase-1, -2 and -4, a thorough characterization of Regnase-3 (Reg-3) has not yet been explored. Here we demonstrate that Reg-3 differs from other family members in terms of NYN/PIN domain features, cellular localization pattern and substrate specificity. Together with Reg-1, the most comprehensively characterized family member, Reg-3 shared IL-6, IER-3 and Reg-1 mRNAs, but not IL-1β mRNA, as substrates. In addition, Reg-3 was found to be the only family member which regulates transcript levels of TNF, a cytokine implicated in chronic inflammatory diseases including psoriasis. Previous meta-analysis of genome-wide association studies revealed Reg-3 to be among new psoriasis susceptibility loci. Here we demonstrate that Reg-3 transcript levels are increased in psoriasis patient skin tissue and in an experimental model of psoriasis, supporting the immunomodulatory role of Reg-3 in psoriasis, possibly through degradation of mRNA for TNF and other factors such as Reg-1. On the other hand, Reg-1 was found to destabilize Reg-3 transcripts, suggesting reciprocal regulation between Reg-3 and Reg-1 in the skin. We found that either Reg-1 or Reg-3 were expressed in human keratinocytes in vitro. However, in contrast to robustly upregulated Reg-1 mRNA levels, Reg-3 expression was not affected in the epidermis of psoriasis patients. Taken together, these data suggest that epidermal levels of Reg-3 are negatively regulated by Reg-1 in psoriasis, and that Reg-1 and Reg-3 are both involved in psoriasis pathophysiology through controlling, at least in part different transcripts.

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Selective Targeting of Epigenetic Readers and Histone Deacetylases in Autoimmune and Inflammatory Diseases: Recent Advances and Future Perspectives

Journal of Personalized Medicine ◽

10.3390/jpm11050336 ◽

2021 ◽

Vol 11 (5) ◽

pp. 336

Author(s):

Mohammed Ghiboub ◽

Ahmed M. I. Elfiky ◽

Menno P. J. de Winther ◽

Nicola R. Harker ◽

David F. Tough ◽

...

Keyword(s):

Histone Deacetylases ◽

Inflammatory Diseases ◽

Selective Inhibition ◽

In Vivo Studies ◽

Beneficial Effects ◽

Domain Specific ◽

Recent Advances ◽

Autoimmune And Inflammatory Diseases

Histone deacetylases (HDACs) and bromodomain-containing proteins (BCPs) play a key role in chromatin remodeling. Based on their ability to regulate inducible gene expression in the context of inflammation and cancer, HDACs and BCPs have been the focus of drug discovery efforts, and numerous small-molecule inhibitors have been developed. However, dose-limiting toxicities of the first generation of inhibitors, which typically target multiple HDACs or BCPs, have limited translation to the clinic. Over the last decade, an increasing effort has been dedicated to designing class-, isoform-, or domain-specific HDAC or BCP inhibitors, as well as developing strategies for cell-specific targeted drug delivery. Selective inhibition of the epigenetic modulators is helping to elucidate the functions of individual epigenetic proteins and has the potential to yield better and safer therapeutic strategies. In accordance with this idea, several in vitro and in vivo studies have reported the ability of more selective HDAC/BCP inhibitors to recapitulate the beneficial effects of pan-inhibitors with less unwanted adverse events. In this review, we summarize the most recent advances with these strategies, discussing advantages and limitations of these approaches as well as some therapeutic perspectives, focusing on autoimmune and inflammatory diseases.

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Strawberry and Achenes Hydroalcoholic Extracts and Their Digested Fractions Efficiently Counteract the AAPH-Induced Oxidative Damage in HepG2 Cells

International Journal of Molecular Sciences ◽

10.3390/ijms19082180 ◽

2018 ◽

Vol 19 (8) ◽

pp. 2180 ◽

Cited By ~ 5

Author(s):

María Ariza ◽

Tamara Forbes-Hernández ◽

Patricia Reboredo-Rodríguez ◽

Sadia Afrin ◽

Massimiliano Gasparrini ◽

...

Keyword(s):

Biological Activity ◽

Oxidative Damage ◽

Hepg2 Cells ◽

In Vitro Digestion ◽

Protective Effects ◽

Beneficial Effects ◽

Positive Effects ◽

Digestion Process ◽

Phytochemical Compounds

Strawberry fruits are highly appreciated by consumers worldwide due to their bright red color, typical aroma, and juicy texture. While the biological activity of the complete fruit has been widely studied, the potential beneficial effects of the achenes (commonly named seeds) remain unknown. In addition, when raw fruit and achenes are consumed, the digestion process could alter the release and absorption of their phytochemical compounds, compromising their bioactivity. In the present work, we evaluated the protective effects against oxidative damage of nondigested and digested extracts from strawberry fruit and achenes in human hepatocellular carcinoma (HepG2) cells. For that purpose, cells were treated with different concentration of the extracts prior to incubation with the stressor agent, AAPH (2,2′-azobis(2-amidinopropane) dihydrochloride). Subsequently, intracellular accumulation of reactive oxygen species (ROS) and the percentage of live, dead, and apoptotic cells were determined. Our results demonstrated that all the evaluated fractions were able to counteract the AAPH-induced damage, suggesting that the achenes also present biological activity. The positive effects of both the raw fruit and achenes were maintained after the in vitro digestion process.

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Fatty acid is a potential agent for bone tissue induction: In vitro and in vivo approach

Experimental Biology and Medicine ◽

10.1177/1535370217731104 ◽

2017 ◽

Vol 242 (18) ◽

pp. 1765-1771 ◽

Cited By ~ 6

Author(s):

Guinea BC Cardoso ◽

Erivelto Chacon ◽

Priscila GL Chacon ◽

Pedro Bordeaux-Rego ◽

Adriana SS Duarte ◽

...

Keyword(s):

Stem Cells ◽

Oleic Acid ◽

Fatty Acid ◽

Bone Tissue ◽

In Vivo Studies ◽

Surrounding Tissue ◽

Bone Induction ◽

Acid Addition

Our hypothesis was to investigate the fatty acid potential as a bone induction factor. In vitro and in vivo studies were performed to evaluate this approach. Oleic acid was used in a 0.5 wt.% concentration. Polycaprolactone was used as the polymeric matrix by combining solvent-casting and particulate-leaching techniques, with a final porosity of 70 wt.%, investigated by SEM images. Contact angle measurements were produced to investigate the influence of oleic acid on polycaprolactone chains. Cell culture was performed using adipocyte-derived stem cells to evaluate biocompatibility and bioactivity properties. In addition, in vivo studies were performed to evaluate the induction potential of oleic acid addition. Adipocyte-derived stem cells were used to provide differentiation after 21 days of culture. Likewise, information were obtained with in vivo data and cellular invagination was observed on both scaffolds (polycaprolactone and polycaprolactone /oleic acid); interestingly, the scaffold with oleic acid addition demonstrated that cellular migrations are not related to the surrounding tissue, indicating bioactive potential. Our hypothesis is that fatty acid may be used as a potential induction factor for bone tissue engineering. The study’s findings indicate oleic acid as a possible agent for bone induction, according to data on cell differentiation, proliferation, and migration. Impact statement The biomaterial combined in this study on bone regeneration is innovative and shows promising results in the treatment of bone lesions. Polycaprolactone (PCL) and oleic acid have been studied separately. In this research, we combined biomaterials to assess the stimulus and the speed of bone healing.

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Curcumin: Could This Compound Be Useful in Pregnancy and Pregnancy-Related Complications?

Nutrients ◽

10.3390/nu12103179 ◽

2020 ◽

Vol 12 (10) ◽

pp. 3179 ◽

Cited By ~ 1

Author(s):

Tiziana Filardi ◽

Rosaria Varì ◽

Elisabetta Ferretti ◽

Alessandra Zicari ◽

Susanna Morano ◽

...

Keyword(s):

Molecular Mechanisms ◽

Curcuma Longa ◽

Growth Disorders ◽

Beneficial Effects ◽

Toxic Agents ◽

Health Promoting ◽

Short And Long Term ◽

The Impact ◽

In Pregnancy

Curcumin, the main polyphenol contained in turmeric root (Curcuma longa), has played a significant role in medicine for centuries. The growing interest in plant-derived substances has led to increased consumption of them also in pregnancy. The pleiotropic and multi-targeting actions of curcumin have made it very attractive as a health-promoting compound. In spite of the beneficial effects observed in various chronic diseases in humans, limited and fragmentary information is currently available about curcumin’s effects on pregnancy and pregnancy-related complications. It is known that immune-metabolic alterations occurring during pregnancy have consequences on both maternal and fetal tissues, leading to short- and long-term complications. The reported anti-inflammatory, antioxidant, antitoxicant, neuroprotective, immunomodulatory, antiapoptotic, antiangiogenic, anti-hypertensive, and antidiabetic properties of curcumin appear to be encouraging, not only for the management of pregnancy-related disorders, including gestational diabetes mellitus (GDM), preeclampsia (PE), depression, preterm birth, and fetal growth disorders but also to contrast damage induced by natural and chemical toxic agents. The current review summarizes the latest data, mostly obtained from animal models and in vitro studies, on the impact of curcumin on the molecular mechanisms involved in pregnancy pathophysiology, with the aim to shed light on the possible beneficial and/or adverse effects of curcumin on pregnancy outcomes.

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Mesenchymal Stromal Cell Secretome for the Treatment of Immune-Mediated Inflammatory Diseases: Latest Trends in Isolation, Content Optimization and Delivery Avenues

Pharmaceutics ◽

10.3390/pharmaceutics13111802 ◽

2021 ◽

Vol 13 (11) ◽

pp. 1802

Author(s):

Elena Munoz-Perez ◽

Ainhoa Gonzalez-Pujana ◽

Manoli Igartua ◽

Edorta Santos-Vizcaino ◽

Rosa Maria Hernandez

Keyword(s):

Stromal Cells ◽

State Of The Art ◽

Inflammatory Diseases ◽

Therapeutic Approaches ◽

Pharmacological Management ◽

Beneficial Effects ◽

New Therapeutic Approaches ◽

Immune Mediated ◽

High Prevalence ◽

Inflammatory Processes

Considering the high prevalence and the complex pharmacological management of immune-mediated inflammatory diseases (IMIDs), the search for new therapeutic approaches for their treatment is vital. Although the immunomodulatory and anti-inflammatory effects of mesenchymal stromal cells (MSCs) have been extensively studied as a potential therapy in this field, direct MSC implantation presents some limitations that could slow down the clinical translation. Since the beneficial effects of MSCs have been mainly attributed to their ability to secrete a plethora of bioactive factors, their secretome has been proposed as a new and promising pathway for the treatment of IMIDs. Formed from soluble factors and extracellular vesicles (EVs), the MSC-derived secretome has been proven to elicit immunomodulatory effects that control the inflammatory processes that occur in IMIDs. This article aims to review the available knowledge on the MSC secretome, evaluating the advances in this field in terms of its composition, production and application, as well as analyzing the pending challenges in the field. Moreover, the latest research involving secretome administration in IMIDs is discussed to provide an updated state-of-the-art for this field. Finally, novel secretome delivery alternatives are reviewed, paying special attention to hydrogel encapsulation as one of the most convenient and promising strategies.

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