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      Matrine Exerts Pharmacological Effects Through Multiple Signaling Pathways: A Comprehensive Review

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          Abstract

          As The main effective monomer of the traditional Chinese medicine Sophora flavescens Ait, matrine has a broad scope of pharmacological activities such as anti-tumor, anti-inflammatory, analgesic, anti-fibrotic, anti-viral, anti-arrhythmia, and improving immune function. These actions explain its therapeutic effects in various types of tumors, cardiopathy, encephalomyelitis, allergic asthma, rheumatoid arthritis (RA), osteoporosis, and central nervous system (CNS) inflammation. Evidence has shown that the mechanism responsible for the pharmacological actions of matrine may be via the activation or inhibition of certain key molecules in several cellular signaling pathways including the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR), transforming growth factor-β/mothers against decapentaplegic homolog (TGF-β/Smad), nuclear factor kappa B (NF-κB), Wnt (wingless/ integration 1)/β-catenin, mitogen-activated protein kinases (MAPKs), and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathways. This review comprehensively summarizes recent studies on the pharmacological mechanisms of matrine to provide a theoretical basis for molecular targeted therapies and further development and utilization of matrine.

          Most cited references150

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          mTOR at the nexus of nutrition, growth, ageing and disease

          The mTOR pathway integrates a diverse set of environmental cues, such as growth factor signals and nutritional status, to direct eukaryotic cell growth. Over the past two and a half decades, mapping of the mTOR signalling landscape has revealed that mTOR controls biomass accumulation and metabolism by modulating key cellular processes, including protein synthesis and autophagy. Given the pathway’s central role in maintaining cellular and physiological homeostasis, dysregulation of mTOR signalling has been implicated in metabolic disorders, neurodegeneration, cancer and ageing. In this Review, we highlight recent advances in our understanding of the complex regulation of the mTOR pathway and discuss its function in the context of physiology, human disease and pharmacological intervention.
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            The PI3K Pathway in Human Disease.

            Phosphoinositide 3-kinase (PI3K) activity is stimulated by diverse oncogenes and growth factor receptors, and elevated PI3K signaling is considered a hallmark of cancer. Many PI3K pathway-targeted therapies have been tested in oncology trials, resulting in regulatory approval of one isoform-selective inhibitor (idelalisib) for treatment of certain blood cancers and a variety of other agents at different stages of development. In parallel to PI3K research by cancer biologists, investigations in other fields have uncovered exciting and often unpredicted roles for PI3K catalytic and regulatory subunits in normal cell function and in disease. Many of these functions impinge upon oncology by influencing the efficacy and toxicity of PI3K-targeted therapies. Here we provide a perspective on the roles of class I PI3Ks in the regulation of cellular metabolism and in immune system functions, two topics closely intertwined with cancer biology. We also discuss recent progress developing PI3K-targeted therapies for treatment of cancer and other diseases.
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              AKT/PKB signaling: navigating downstream.

              The serine/threonine kinase Akt, also known as protein kinase B (PKB), is a central node in cell signaling downstream of growth factors, cytokines, and other cellular stimuli. Aberrant loss or gain of Akt activation underlies the pathophysiological properties of a variety of complex diseases, including type-2 diabetes and cancer. Here, we review the molecular properties of Akt and the approaches used to characterize its true cellular targets. In addition, we discuss those Akt substrates that are most likely to contribute to the diverse cellular roles of Akt, which include cell survival, growth, proliferation, angiogenesis, metabolism, and migration.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                dddt
                Drug Design, Development and Therapy
                Dove
                1177-8881
                01 March 2022
                2022
                : 16
                : 533-569
                Affiliations
                [1 ]Department of Pharmacy, the Affiliated Hospital of Yangzhou University, Yangzhou University , Yangzhou, 225012, People’s Republic of China
                [2 ]Medical College, Yangzhou University , Yangzhou, 225001, People’s Republic of China
                [3 ]Department of Neurosurgery, the Affiliated Hospital of Yangzhou University, Yangzhou University , Yangzhou, 225012, People’s Republic of China
                [4 ]Department of Central Laboratory, the Affiliated Hospital of Yangzhou University, Yangzhou University , Yangzhou, 225012, People’s Republic of China
                Author notes
                Correspondence: Qiu Du, Department of Neurosurgery, the Affiliated Hospital of Yangzhou University, Yangzhou University , 368 Hanjiang Middle Road, Yangzhou, 225012, People’s Republic of China, Email 092102@yzu.edu.cn
                Yuan Xu, Department of pharmacy, the Affiliated Hospital of Yangzhou University, Yangzhou University , 368 Hanjiang Middle Road, Yangzhou, 225012, People’s Republic of China, Email feebyxuyuan@163.com
                [*]

                These authors contributed equally to this work

                Author information
                https://orcid.org/http://orcid.org/0000-0002-4882-221X
                Article
                349678
                10.2147/DDDT.S349678
                8898013
                35256842
                7caf08cd-8192-4fa9-9e21-ac9b74257cfd
                © 2022 Lin et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 23 November 2021
                : 03 February 2022
                Page count
                Figures: 0, Tables: 8, References: 150, Pages: 37
                Funding
                Funded by: the Natural Science Foundation of Jiangsu Province;
                Funded by: the Natural Science Research Project of the Higher Educational Institutions of Jiangsu Province;
                Funded by: the Yangzhou Science and Technology Planning Project;
                This work was supported by the Natural Science Foundation of Jiangsu Province (BK20200936), the Natural Science Research Project of the Higher Educational Institutions of Jiangsu Province (20KJB320007), and the Yangzhou Science and Technology Planning Project (YZ2021082).
                Categories
                Review

                Pharmacology & Pharmaceutical medicine
                matrine,pharmacological effects,signaling pathways,review

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