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      Protective Effects of Caesalpinia sappan Linn. and Its Bioactive Compounds on Cardiovascular Organs

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          Abstract

          Cardiovascular diseases are the leading cause of death worldwide. The long-term aim of cardiovascular disease therapy is to reduce the mortality rate and decelerate the progression of cardiovascular organ damage. Current therapies focus on recovering heart function and reducing risk factors such as hyperglycemia and dyslipidemia. However, oxidative stress and inflammation are important causes of further damage to cardiovascular organs. Caesalpinia sappan Linn. (Fabaceae), a flowering tree native to tropical Asia, has antioxidant and anti-inflammatory properties. It is used as a natural dye to color food and beverages and as a traditional treatment for diarrhea, diabetes, and blood stasis. The phytochemical compounds in C. sappan, mainly the homoisoflavonoids brazilin, sappanone A, protosappanin, and hematoxylin, can potentially be used to protect cardiovascular organs. This review aims to provide updates on recent developments in research on C. sappan in relation to treatment of cardiovascular diseases. Many studies have reported protective effects of the plant’s bioactive compounds that reduce cardiac damage and enhance vasorelaxation. For example, brazilin and sappanone A have an impact on molecular and cellular changes in cardiovascular disease pathogenesis, mainly by modulating oxidative, inflammatory, and apoptotic signaling pathways. Therefore, bioactive compounds of C. sappan have the potential to be developed as therapeutic agents to combat cardiovascular diseases like myocardial infarction and vascular disease. This review could help further the understanding of the possible modulatory role of the compounds in cardiovascular diseases, thereby facilitating future studies.

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          Most cited references102

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          Nrf2 signaling pathway: Pivotal roles in inflammation.

          Inflammation is the most common feature of many chronic diseases and complications, while playing critical roles in carcinogenesis. Several studies have demonstrated that Nrf2 contributes to the anti-inflammatory process by orchestrating the recruitment of inflammatory cells and regulating gene expression through the antioxidant response element (ARE). The Keap1 (Kelch-like ECH-associated protein)/Nrf2 (NF-E2 p45-related factor 2)/ARE signaling pathway mainly regulates anti-inflammatory gene expression and inhibits the progression of inflammation. Therefore, the identification of new Nrf2-dependent anti-inflammatory phytochemicals has become a key point in drug discovery. In this review, we discuss the members of the Keap1/Nrf2/ARE signal pathway and its downstream genes, the effects of this pathway on animal models of inflammatory diseases, and crosstalk with the NF-κB pathway. In addition we also discuss about the regulation of NLRP3 inflammasome by Nrf2. Besides this, we summarize the current scenario of the development of anti-inflammatory phytochemicals and others that mediate the Nrf2/ARE signaling pathway.
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            ROS and ROS-Mediated Cellular Signaling

            It has long been recognized that an increase of reactive oxygen species (ROS) can modify the cell-signaling proteins and have functional consequences, which successively mediate pathological processes such as atherosclerosis, diabetes, unchecked growth, neurodegeneration, inflammation, and aging. While numerous articles have demonstrated the impacts of ROS on various signaling pathways and clarify the mechanism of action of cell-signaling proteins, their influence on the level of intracellular ROS, and their complex interactions among multiple ROS associated signaling pathways, the systemic summary is necessary. In this review paper, we particularly focus on the pattern of the generation and homeostasis of intracellular ROS, the mechanisms and targets of ROS impacting on cell-signaling proteins (NF-κB, MAPKs, Keap1-Nrf2-ARE, and PI3K-Akt), ion channels and transporters (Ca2+ and mPTP), and modifying protein kinase and Ubiquitination/Proteasome System.
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              Perforin and granzymes: function, dysfunction and human pathology.

              A defining property of cytotoxic lymphocytes is their expression and regulated secretion of potent toxins, including the pore-forming protein perforin and serine protease granzymes. Until recently, mechanisms of pore formation and granzyme transfer into the target cell were poorly understood, but advances in structural and cellular biology have now begun to unravel how synergy between perforin and granzymes brings about target cell death. These and other advances are demonstrating the surprisingly broad pathophysiological roles of the perforin–granzyme pathway, and this has important implications for understanding immune homeostasis and for developing immunotherapies for cancer and other diseases. In particular, we are beginning to define and understand a range of human diseases that are associated with a failure to deliver active perforin to target cells. In this Review, we discuss the current understanding of the structural, cellular and clinical aspects of perforin and granzyme biology.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                15 September 2021
                2021
                : 12
                : 725745
                Affiliations
                [ 1 ]Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Jatinangor, Indonesia
                [ 2 ]Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jatinangor, Indonesia
                [ 3 ]Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
                Author notes

                Edited by: Andrés Navarrete, Universidad Nacional Autónoma de México, Mexico

                Reviewed by: Elizabeth Arlen Pineda Peña, National Autonomous University of Mexico, Mexico

                Priyia Pusparajah, Monash University Malaysia, Malaysia

                *Correspondence: Yusof Kamisah, kamisah_y@ 123456yahoo.com

                This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology

                Article
                725745
                10.3389/fphar.2021.725745
                8479160
                34603037
                c36220ff-00ca-4cdd-9679-25de6a661b9c
                Copyright © 2021 Syamsunarno, Safitri and Kamisah.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 15 June 2021
                : 31 August 2021
                Funding
                Funded by: Universiti Kebangsaan Malaysia , doi 10.13039/501100004515;
                Award ID: FF-2019-480 FF-2019-480/1
                Funded by: Kementerian Riset, Teknologi dan Pendidikan Tinggi , doi 10.13039/501100010447;
                Award ID: 1827/UN6.3.1/LT/2020
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                caesalpinia sappan,brazilin,sappanone a,brazilein,ischemia/reperfusion injury,vasorelaxation,heart,vascular

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