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      Hormesis and Ginseng: Ginseng Mixtures and Individual Constituents Commonly Display Hormesis Dose Responses, Especially for Neuroprotective Effects

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          Abstract

          This paper demonstrates that ginseng mixtures and individual ginseng chemical constituents commonly induce hormetic dose responses in numerous biological models for endpoints of biomedical and clinical relevance, typically providing a mechanistic framework. The principal focus of ginseng hormesis-related research has been directed toward enhancing neuroprotection against conditions such as Alzheimer’s and Parkinson’s Diseases, stroke damage, as well as enhancing spinal cord and peripheral neuronal damage repair and reducing pain. Ginseng was also shown to reduce symptoms of diabetes, prevent cardiovascular system damage, protect the kidney from toxicities due to immune suppressant drugs, and prevent corneal damage, amongst other examples. These findings complement similar hormetic-based chemoprotective reports for other widely used dietary-type supplements such as curcumin, ginkgo biloba, and green tea. These findings, which provide further support for the generality of the hormetic dose response in the biomedical literature, have potentially important public health and clinical implications.

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          Most cited references157

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          Ginseng pharmacology: multiple constituents and multiple actions.

          Ginseng is a highly valued herb in the Far East and has gained popularity in the West during the last decade. There is extensive literature on the beneficial effects of ginseng and its constituents. The major active components of ginseng are ginsenosides, a diverse group of steroidal saponins, which demonstrate the ability to target a myriad of tissues, producing an array of pharmacological responses. However, many mechanisms of ginsenoside activity still remain unknown. Since ginsenosides and other constituents of ginseng produce effects that are different from one another, and a single ginsenoside initiates multiple actions in the same tissue, the overall pharmacology of ginseng is complex. The ability of ginsenosides to independently target multireceptor systems at the plasma membrane, as well as to activate intracellular steroid receptors, may explain some pharmacological effects. This commentary aims to review selected effects of ginseng and ginsenosides and describe their possible modes of action. Structural variability of ginsenosides, structural and functional relationship to steroids, and potential targets of action are discussed.
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            How does hormesis impact biology, toxicology, and medicine?

            Hormesis refers to adaptive responses of biological systems to moderate environmental or self-imposed challenges through which the system improves its functionality and/or tolerance to more severe challenges. The past two decades have witnessed an expanding recognition of the concept of hormesis, elucidation of its evolutionary foundations, and underlying cellular and molecular mechanisms, and practical applications to improve quality of life. To better inform future basic and applied research, we organized and re-evaluated recent hormesis-related findings with the intent of incorporating new knowledge of biological mechanisms, and providing fundamental insights into the biological, biomedical and risk assessment implications of hormesis. As the literature on hormesis is expanding rapidly into new areas of basic and applied research, it is important to provide refined conceptualization of hormesis to aid in designing and interpreting future studies. Here, we establish a working compartmentalization of hormesis into ten categories that provide an integrated understanding of the biological meaning and applications of hormesis.
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              Hormetic mechanisms.

              This article provides the first extensive documentation of mechanisms of hormetic dose/concentration responses. The mechanisms selected were principally those mediated via receptor and/or cell signaling pathways. Mechanisms are reported for greater than 100 agents affecting nearly 400 dose/concentration responses from a wide range of chemical classes, affecting a broad range of cell types and endpoints. Regardless of the model (i.e. in vitro or in vivo), inducing agent, endpoint, or receptor/cell signaling pathway mediated mechanism, the quantitative features of the hormetic dose/concentration responses are similar, suggesting that the magnitude of the response is a measure of biological plasticity, within a broad range of biological contexts. These findings represent an important advance in the understanding of the hormetic dose/concentration response, its generalizability and potential biomedical applications, including drug discovery/efficacy assessment and the risk assessment process.
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                11 June 2020
                June 2020
                : 25
                : 11
                : 2719
                Affiliations
                Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA 01003, USA; edwardc@ 123456schoolph.umass.edu ; Tel.: +1-413-545-3164
                Article
                molecules-25-02719
                10.3390/molecules25112719
                7321326
                32545419
                8abb2273-b1fd-4f32-a241-a925cd9bf233
                © 2020 by the author.

                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
                : 14 May 2020
                : 08 June 2020
                Categories
                Review

                hormesis,hormetic,ginseng,biphasic,neuroprotection,aging,alzheimer’s disease,parkinson’s disease,wound healing,preconditioning

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