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      Dietary Phytochemicals: Natural Swords Combating Inflammation and Oxidation-Mediated Degenerative Diseases

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          Abstract

          Cumulatively, degenerative disease is one of the most fatal groups of diseases, and it contributes to the mortality and poor quality of life in the world while increasing the economic burden of the sufferers. Oxidative stress and inflammation are the major pathogenic causes of degenerative diseases such as rheumatoid arthritis (RA), diabetes mellitus (DM), and cardiovascular disease (CVD). Although a number of synthetic medications are used to treat these diseases, none of the current regimens are completely safe. Phytochemicals (polyphenols, carotenoids, anthocyanins, alkaloids, glycosides, saponins, and terpenes) from natural products such as dietary fruits, vegetables, and spices are potential sources of alternative medications to attenuate the oxidative stress and inflammation associated with degenerative diseases. Based on in vitro, in vivo, and clinical trials, some of these active compounds have shown good promise for development into novel agents for treating RA, DM, and CVD by targeting oxidative stress and inflammation. In this review, phytochemicals from natural products with the potential of ameliorating degenerative disease involving the bone, metabolism, and the heart are described.

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          Most cited references170

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          Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes.

          There is increasing evidence that an ongoing cytokine-induced acute-phase response (sometimes called low-grade inflammation, but part of a widespread activation of the innate immune system) is closely involved in the pathogenesis of type 2 diabetes and associated complications such as dyslipidemia and atherosclerosis. Elevated circulating inflammatory markers such as C-reactive protein and interleukin-6 predict the development of type 2 diabetes, and several drugs with anti-inflammatory properties lower both acute-phase reactants and glycemia (aspirin and thiazolidinediones) and possibly decrease the risk of developing type 2 diabetes (statins). Among the risk factors for type 2 diabetes, which are also known to be associated with activated innate immunity, are age, inactivity, certain dietary components, smoking, psychological stress, and low birth weight. Activated immunity may be the common antecedent of both type 2 diabetes and atherosclerosis, which probably develop in parallel. Other features of type 2 diabetes, such as fatigue, sleep disturbance, and depression, are likely to be at least partly due to hypercytokinemia and activated innate immunity. Further research is needed to confirm and clarify the role of innate immunity in type 2 diabetes, particularly the extent to which inflammation in type 2 diabetes is a primary abnormality or partly secondary to hyperglycemia, obesity, atherosclerosis, or other common features of the disease.
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            Matrix metalloproteinases: role in arthritis.

            The irreversible destruction of the cartilage, tendon, and bone that comprise synovial joints is the hallmark of both rheumatoid arthritis (RA) and osteoarthritis (OA). While cartilage is made up of proteoglycans and type II collagen, tendon and bone are composed primarily of type I collagen. RA is an autoimmune disease afflicting numerous joints throughout the body; in contrast, OA develops in a small number of joints, usually resulting from chronic overuse or injury. In both diseases, inflammatory cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) stimulate the production of matrix metalloproteinases (MMPs), enzymes that can degrade all components of the extracellular matrix. The collagenases, MMP-1 and MMP-13, have predominant roles in RA and OA because they are rate limiting in the process of collagen degradation. MMP-1 is produced primarily by the synovial cells that line the joints, and MMP-13 is a product of the chondrocytes that reside in the cartilage. In addition to collagen, MMP-13 also degrades the proteoglycan molecule, aggrecan, giving it a dual role in matrix destruction. Expression of other MMPs such as MMP-2, MMP-3 and MMP-9, is also elevated in arthritis and these enzymes degrade non-collagen matrix components of the joints. Significant effort has been expended in attempts to design effective inhibitors of MMP activity and/or synthesis with the goal of curbing connective tissues destruction within the joints. To date, however, no effective clinical inhibitors exist. Increasing our knowledge of the crystal structures of these enzymes and of the signal transduction pathways and molecular mechanisms that control MMP gene expression may provide new opportunities for the development of therapeutics to prevent the joint destruction seen in arthritis.
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              Targeting inflammation in the treatment of type 2 diabetes: time to start.

              The role of inflammation in the pathogenesis of type 2 diabetes and associated complications is now well established. Several conditions that are driven by inflammatory processes are also associated with diabetes, including rheumatoid arthritis, gout, psoriasis and Crohn's disease, and various anti-inflammatory drugs have been approved or are in late stages of development for the treatment of these conditions. This review discusses the rationale for the use of some of these anti-inflammatory treatments in patients with diabetes and what we could expect from their use. Future immunomodulatory treatments may not target a specific disease, but could instead act on a dysfunctional pathway that causes several conditions associated with the metabolic syndrome.
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                Author and article information

                Journal
                Oxid Med Cell Longev
                Oxid Med Cell Longev
                OMCL
                Oxidative Medicine and Cellular Longevity
                Hindawi Publishing Corporation
                1942-0900
                1942-0994
                2016
                19 September 2016
                : 2016
                : 5137431
                Affiliations
                1Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia
                2Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka 1342, Bangladesh
                3King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80216, Jeddah, Saudi Arabia
                4Enzymoics, 7 Peterlee Place, Hebersham, NSW 2770, Australia
                5Novel Global Community Educational Foundation, 7 Peterlee Place, Hebersham, NSW 2770, Australia
                Author notes
                *Md. Asiful Islam: ayoncx70@ 123456yahoo.com and
                *Siew Hua Gan: shgan@ 123456usm.my

                Academic Editor: Yolanda de Pablo

                Author information
                http://orcid.org/0000-0001-5937-6473
                http://orcid.org/0000-0002-2196-2044
                http://orcid.org/0000-0003-4316-5211
                http://orcid.org/0000-0002-8358-0252
                http://orcid.org/0000-0003-0088-0565
                http://orcid.org/0000-0001-6470-3651
                Article
                10.1155/2016/5137431
                5046019
                27721914
                5c1ddb26-5880-45af-b63e-0c7b0630b142
                Copyright © 2016 Md. Asiful Islam et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 May 2016
                : 8 July 2016
                : 22 August 2016
                Categories
                Review Article

                Molecular medicine
                Molecular medicine

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