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      Relationship of the Phytochemicals from Coffee and Cocoa By-Products with their Potential to Modulate Biomarkers of Metabolic Syndrome In Vitro

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          Abstract

          This study aimed to compare the phytochemicals from coffee and cocoa by-products and their relationship with the potential for reducing markers of inflammation, oxidative stress, adipogenesis, and insulin resistance in vitro. We characterized the phytochemical profile of extracts from coffee husk, coffee silverskin, and cocoa shell and evaluated their in vitro biological activity in RAW264.7 macrophages and 3T3-L1 adipocytes. Pearson correlations and principal component regressions were performed to find the contribution of phytochemicals and underlying mechanisms of action. Coffee husk and silverskin extracts were mainly composed of caffeine and chlorogenic acid. Major components in cocoa shell included theobromine and protocatechuic acid. Both coffee and cocoa by-product extracts effectively reduced inflammatory markers in macrophages and adipocytes (NO, PGE 2, TNF-α, MCP-1, and IL-6) and the production of reactive oxygen species (21.5–66.4%). Protocatechuic and chlorogenic acids, together with caffeine, were suggested as main contributors against inflammation and oxidative stress. Furthermore, extracts reduced lipid accumulation (4.1–49.1%) in adipocytes by regulating lipolysis and inducing adipocyte browning. Gallic and chlorogenic acids were associated with reduced adipogenesis, and caffeine with adipocyte browning. Extracts from coffee and cocoa by-products also modulated the phosphorylation of insulin receptor signaling pathway and stimulated GLUT-4 translocation (52.4–72.9%), increasing glucose uptake. The insulin-sensitizing potential of the extracts was mainly associated with protocatechuic acid. For the first time, we identified the phytochemicals from coffee and cocoa by-products and offered new insights into their associations with biomarkers of inflammation, oxidative stress, adipogenesis, and insulin resistance in vitro.

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          Most cited references55

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          Role of nitric oxide in inflammatory diseases.

          Nitric oxide (NO) is a signaling molecule that plays a key role in the pathogenesis of inflammation. It gives an anti-inflammatory effect under normal physiological conditions. On the other hand, NO is considered as a pro-inflammatory mediator that induces inflammation due to over production in abnormal situations. NO is synthesized and released into the endothelial cells by the help of NOSs that convert arginine into citrulline producing NO in the process. Oxygen and NADPH are necessary co-factors in such conversion. NO is believed to induce vasodilatation in cardiovascular system and furthermore, it involves in immune responses by cytokine-activated macrophages, which release NO in high concentrations. In addition, NO is a potent neurotransmitter at the neuron synapses and contributes to the regulation of apoptosis. NO is involved in the pathogenesis of inflammatory disorders of the joint, gut and lungs. Therefore, NO inhibitors represent important therapeutic advance in the management of inflammatory diseases. Selective NO biosynthesis inhibitors and synthetic arginine analogues are proved to be used for the treatment of NO-induced inflammation. Finally, the undesired effects of NO are due to its impaired production, including in short: vasoconstriction, inflammation and tissue damage.
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            The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta.

            NF-kappaB comprises a family of cellular transcription factors that are involved in the inducible expression of a variety of cellular genes that regulate the inflammatory response. NF-kappaB is sequestered in the cytoplasm by inhibitory proteins, I(kappa)B, which are phosphorylated by a cellular kinase complex known as IKK. IKK is made up of two kinases, IKK-alpha and IKK-beta, which phosphorylate I(kappa)B, leading to its degradation and translocation of NF-kappaB to the nucleus. IKK kinase activity is stimulated when cells are exposed to the cytokine TNF-alpha or by overexpression of the cellular kinases MEKK1 and NIK. Here we demonstrate that the anti-inflammatory agents aspirin and sodium salicylate specifically inhibit IKK-beta activity in vitro and in vivo. The mechanism of aspirin and sodium salicylate inhibition is due to binding of these agents to IKK-beta to reduce ATP binding. Our results indicate that the anti-inflammatory properties of aspirin and salicylate are mediated in part by their specific inhibition of IKK-beta, thereby preventing activation by NF-kappaB of genes involved in the pathogenesis of the inflammatory response.
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              Food based dietary patterns and chronic disease prevention

              Matthias B Schulze and colleagues discuss current knowledge on the associations between dietary patterns and cancer, coronary heart disease, stroke, and type 2 diabetes, focusing on areas of uncertainty and future research directions
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                Author and article information

                Journal
                Antioxidants (Basel)
                Antioxidants (Basel)
                antioxidants
                Antioxidants
                MDPI
                2076-3921
                05 August 2019
                August 2019
                : 8
                : 8
                : 279
                Affiliations
                [1 ]Institute of Food Science Research, CIAL (UAM-CSIC), 28049 Madrid, Spain
                [2 ]Department of Agricultural Chemistry and Food Science, Universidad Autónoma de Madrid, 28049 Madrid, Spain
                [3 ]Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
                [4 ]College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310000, China
                Author notes
                [* ]Correspondence: edemejia@ 123456illinois.edu ; Tel.: +1-217-244-3196
                Author information
                https://orcid.org/0000-0003-1034-1290
                Article
                antioxidants-08-00279
                10.3390/antiox8080279
                6721099
                31387271
                5487d414-b5e0-4812-801b-dc4f1bf64964
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 08 July 2019
                : 02 August 2019
                Categories
                Article

                phytochemicals,inflammation,oxidative stress,adipogenesis,insulin resistance,coffee by-products,cocoa by-products

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