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The aim of this review was to summarize the growing knowledge about common adaptogenic plants used in various traditional medical systems (TMS) and conventional medicine and to provide a modern rationale for their use in the treatment of stress\u2010induced and aging\u2010related disorders. Adaptogens have pharmacologically pleiotropic effects on the neuroendocrine\u2010immune system, which explain their traditional use for the treatment of a wide range of conditions. They exhibit a biphasic dose\u2010effect response: at low doses they function as mild stress\u2010mimetics, which activate the adaptive stress\u2010response signaling pathways to cope with severe stress. That is in line with their traditional use for preventing premature aging and to maintain good health and vitality. However, the potential of adaptogens remains poorly explored. Treatment of stress and aging\u2010related diseases require novel approaches. Some combinations of adaptogenic plants provide unique effects due to their synergistic interactions in organisms not obtainable by any ingredient independently. Further progress in this field needs to focus on discovering new combinations of adaptogens based on traditional medical concepts. Robust and rigorous approaches including network pharmacology and systems pharmacology could help in analyzing potential synergistic effects and, more broadly, future uses of adaptogens. In conclusion, the evolution of the adaptogenic concept has led back to basics of TMS and a new level of understanding of holistic approach. It provides a rationale for their use in stress\u2010induced and aging\u2010related diseases.<\/jats:p>","DOI":"10.1002\/med.21743","type":"journal-article","created":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T05:25:34Z","timestamp":1603689934000},"page":"630-703","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":295,"title":["Evolution of the adaptogenic concept from traditional use to medical systems: Pharmacology of stress\u2010 and aging\u2010related diseases"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8467-4525","authenticated-orcid":false,"given":"Alexander G.","family":"Panossian","sequence":"first","affiliation":[{"name":"Phytomed AB Vaxtorp Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2637-1681","authenticated-orcid":false,"given":"Thomas","family":"Efferth","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry Johannes Gutenberg University Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander N.","family":"Shikov","sequence":"additional","affiliation":[{"name":"Department of technology of dosage forms Saint\u2010Petersburg State Chemical\u2010Pharmaceutical University St. Petersburg Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga N.","family":"Pozharitskaya","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Murmansk Marine Biological Institute of the Kola Science Center of the Russian Academy of Sciences (MMBI KSC RAS) Murmansk Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenny","family":"Kuchta","sequence":"additional","affiliation":[{"name":"Department of Far Eastern Medicine, Clinic for Gastroenterology and Gastrointestinal Oncology University Medical Center G\u00f6ttingen G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pulok K.","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, School of Natural Product Studies Jadavpur University Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhadip","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, School of Natural Product Studies Jadavpur University Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Heinrich","sequence":"additional","affiliation":[{"name":"Research Cluster Biodiversity and Medicines, UCL School of Pharmacy, Centre for Pharmacognosy and Phytotherapy University of London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanying","family":"Wu","sequence":"additional","affiliation":[{"name":"Shanghai Research Center for TCM Modernization, Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De\u2010an","family":"Guo","sequence":"additional","affiliation":[{"name":"Shanghai Research Center for TCM Modernization, Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hildebert","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Center for Pharma Research Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10,25]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"EMA\/HMPC\/232100\/2011. 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