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      Natural Drugs as a Treatment Strategy for Cardiovascular Disease through the Regulation of Oxidative Stress

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          Abstract

          Oxidative stress (OS) refers to the physiological imbalance between oxidative and antioxidative processes leading to increased oxidation, which then results in the inflammatory infiltration of neutrophils, increased protease secretion, and the production of a large number of oxidative intermediates. Oxidative stress is considered an important factor in the pathogenesis of cardiovascular disease (CVD). At present, active components of Chinese herbal medicines (CHMs) have been widely used for the treatment of CVD, including coronary heart disease and hypertension. Since the discovery of artemisinin for the treatment of malaria by Nobel laureate Youyou Tu, the therapeutic effects of active components of CHM on various diseases have been widely investigated by the medical community. It has been found that various active CHM components can regulate oxidative stress and the circulatory system, including ginsenoside, astragaloside, and resveratrol. This paper reviews advances in the use of active CHM components that modulate oxidative stress, suggesting potential drugs for the treatment of various CVDs.

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          ROS and redox signaling in myocardial ischemia-reperfusion injury and cardioprotection.

          Ischemia-reperfusion (IR) injury is central to the pathology of major cardiovascular diseases, such as stroke and myocardial infarction. IR injury is mediated by several factors including the elevated production of reactive oxygen species (ROS), which occurs particularly at reperfusion. The mitochondrial respiratory chain and NADPH oxidases of the NOX family are major sources of ROS in cardiomyocytes. The first part of this review discusses recent findings and controversies on the mechanisms of superoxide production by the mitochondrial electron transport chain during IR injury, as well as the contribution of the NOX isoforms expressed in cardiomyocytes, NOX1, NOX2 and NOX4, to this damage. It then focuses on the effects of ROS on the opening of the mitochondrial permeability transition pore (mPTP), an inner membrane non-selective pore that causes irreversible damage to the heart. The second part analyzes the redox mechanisms of cardiomyocyte mitochondrial protection; specifically, the activation of the hypoxia-inducible factor (HIF) pathway and the antioxidant transcription factor Nrf2, which are both regulated by the cellular redox state. Redox mechanisms involved in ischemic preconditioning, one of the most effective ways of protecting the heart against IR injury, are also reviewed. Interestingly, several of these protective pathways converge on the inhibition of mPTP opening during reperfusion. Finally, the clinical and translational implications of these cardioprotective mechanisms are discussed.
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            Inflammasome activation of cardiac fibroblasts is essential for myocardial ischemia/reperfusion injury.

            Background- Inflammation plays a key role in the pathophysiology of myocardial ischemia/reperfusion (I/R) injury; however, the mechanism by which myocardial I/R induces inflammation remains unclear. Recent evidence indicates that a sterile inflammatory response triggered by tissue damage is mediated through a multiple-protein complex called the inflammasome. Therefore, we hypothesized that the inflammasome is an initial sensor for danger signal(s) in myocardial I/R injury. Methods and Results- We demonstrate that inflammasome activation in cardiac fibroblasts, but not in cardiomyocytes, is crucially involved in the initial inflammatory response after myocardial I/R injury. We found that inflammasomes are formed by I/R and that its subsequent activation of inflammasomes leads to interleukin-1β production, resulting in inflammatory responses such as inflammatory cell infiltration and cytokine expression in the heart. In mice deficient for apoptosis-associated speck-like adaptor protein and caspase-1, these inflammatory responses and subsequent injuries, including infarct development and myocardial fibrosis and dysfunction, were markedly diminished. Bone marrow transplantation experiments with apoptosis-associated speck-like adaptor protein-deficient mice revealed that inflammasome activation in bone marrow cells and myocardial resident cells such as cardiomyocytes or cardiac fibroblasts plays an important role in myocardial I/R injury. In vitro experiments revealed that hypoxia/reoxygenation stimulated inflammasome activation in cardiac fibroblasts, but not in cardiomyocytes, and that hypoxia/reoxygenation-induced activation was mediated through reactive oxygen species production and potassium efflux. Conclusions- Our results demonstrate the molecular basis for the initial inflammatory response after I/R and suggest that the inflammasome is a potential novel therapeutic target for preventing myocardial I/R injury.
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              The role of natural products in modern drug discovery.

              Abstract: The global medicine market is about 1.1 trillion US dollars. About 35 percent of medicines have originated from natural products. Brazil presents the largest biodiversity in the world, with more than 50,000 species of higher plants. However, few innovative products have been developed in Brazil from active constituents derived from the Brazilian biodiversity. Scientific evidences on plants and venoms have been internationally published by Brazilian scientists over the last 4 decades; but few examples of innovative products are commercially available. Few examples include the anti-hypertensive drug captopril first identified in the venom of the Brazilian viper Bothrops jararaca by Professor Sergio Ferreira; and some phytotherapeutic agents such as Acheflan®, Syntocalmy® and Melagrião® produced by standardized plant extracts with scientific proof of safety, efficacy and quality. Still, only Acheflan® and Melagrião® are obtained from native Brazilian plants. Several issues contribute to the lack of innovative products from the Brazilian biodiversity, but in my opinion, the most challenging ones are i) the lack of specific regulations to allow researchers and companies to access biodiversity for the purposes of scientific and technological innovation; and ii) the absence of a long-term government program to support research and innovation in this field.
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                Author and article information

                Contributors
                Journal
                Oxid Med Cell Longev
                Oxid Med Cell Longev
                OMCL
                Oxidative Medicine and Cellular Longevity
                Hindawi
                1942-0900
                1942-0994
                2020
                27 September 2020
                : 2020
                : 5430407
                Affiliations
                1National Resource Center for Chinese Materia Medica, State Key Laboratory Breeding Base of Dao-di Herbs, China Academy of Chinese Medical Sciences, Beijing 100700, China
                2Guang'anmen Hospital, Chinese Academy of Traditional Chinese Medicine, Beijing 100053, China
                3Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, China
                Author notes

                Academic Editor: Yaozu Xiang

                Author information
                https://orcid.org/0000-0002-7301-0440
                https://orcid.org/0000-0002-4561-5258
                Article
                10.1155/2020/5430407
                7537704
                33062142
                b4b02488-2706-43b6-8934-124c51f5877a
                Copyright © 2020 Xing Chang 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
                : 4 June 2020
                : 2 September 2020
                : 9 September 2020
                Funding
                Funded by: Key Project at Central Government Level: The Ability Establishment of Sustainable Use for Valuable Chinese Medicine Resources
                Award ID: 2060302
                Categories
                Review Article

                Molecular medicine
                Molecular medicine

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