CoChat
Sign Up
Cited by 347Medicinal Plants and Bioactive CompoundsPhytochemicals and Medicinal PlantsGinseng Biological Effects and Applications

Evolution of the adaptogenic concept from traditional use to medical systems: Pharmacology of stress and aging related diseases

Open access
Panossian, Alexander G., Efferth, Thomas, Shikov, Alexander N., Pozharitskaya, Olga N., Kuchta, Kenny, Mukherjee, Pulok K., Banerjee, Subhadip, Heinrich, Michael +3 more·2021·Medicinal Research Reviews
DOI 10.1002/med.21743PMC PMC7756641
Open this paper in CoChat — free accountOpen PDF

Abstract

Adaptogens comprise a category of herbal medicinal and nutritional products promoting adaptability, resilience, and survival of living organisms in stress. 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-induced and aging-related disorders. Adaptogens have pharmacologically pleiotropic effects on the neuroendocrine-immune system, which explain their traditional use for the treatment of a wide range of conditions. They exhibit a biphasic dose-effect response: at low doses they function as mild stress-mimetics, which activate the adaptive stress-response 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-related 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-induced and aging-related diseases.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1002/med.21743

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Plant adaptogens have a rich phytochemical composition, with important phytochemicals including triterpenoid saponins, phytosterols and ecdysone, lignans, alkaloids, flavonoids, and vitamins.

    “Plant adaptogens have very rich phytochemical composition. Some of the most important phytochemicals with adaptogenic properties are: triterpenoid saponins (in Panax ginseng—ginsenosides; in Eleutherococcus senticosus—eleutherosides); phytosterols and ecdysone (in Rhaponticum carthamoides); lignans (in Schisandra chinensis); alkaloids; flavonoids, vitamins, etc. [4,8,9].”

    From Plant Adaptogens—History and Future Perspectives (2021) · cites this paper as [4]

  • Current and potential uses of these medicinal plants are associated with mental diseases and behavioural disorders, cognitive function, and stress-induced diseases such as anxiety, cardiovascular diseases, and diabetes.

    “Current and potential uses of these medicinal plants are associated with mental diseases and behavioural disorders, cognitive function and stress-induced diseases (anxiety, cardiovascular diseases, diabetes) [4,9,15,16,17,18,19,20].”

    From Plant Adaptogens—History and Future Perspectives (2021) · cites this paper as [4]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 572 · Cited by 347

Research works printed but not linked: 68

  1. [6]Lazarev NV. General and specific in action of pharmacological agents. Farmacol Toxicol. 1958; 21: 81‐ 86.
  2. [7]Lazarev NV, Ljublina EI, Ljublina MA. State of nonspecific resistance. Patol Fiziol Exp Terapia. 1959; 3: 16‐ 21. 14414794
  3. [9]Farnsworth NR, Waller D, Strelkova LM. Use of Eleutherococcus senticosus in United States: problems, prospects and literature update. Proceedings of the Second International Symposium on Eleutherococcus Vladivostok: Far Eastern Scientific Center, USSR Academy of Sciences; 1986: 47‐ 51.
  4. [60]Wiegant FAC, Limandjaja G, de Poot SAH. Plant adaptogens activate cellular adaptive mechanisms by causing mild damage In: Lukyanova L, Takeda N, Singal PK, eds. Adaptation Biology and Medicine, vol. 5: Health Potentials. New Delhi: Narosa Publishing House; 2008: 319‐ 332.
  5. [64]Rossijskij DM. Schisandra chinensis as a stimulant and tonic agent. Naval doctor. 1944; 4: 18‐ 22.
  6. [65]Karo VI. The geographic study of Schizandra stimulating effect. Scientific Papers of 3rd Year Students of the Naval Medical School. 1945; 3: 30‐ 33.
  7. [66]Zhestyanikov VD. Some data on the effect of the Far East Schizandra on the CNS. Scientific Papers of 3rd Year Students of the Naval Medical School. 1945; 3: 24‐ 29.
  8. [68]Lebedev AA. Schizandrin—a new stimulant from Schizandra chinensis fruits. [dissertation]. Tashkent: Tashkent University; 1967.
  9. [70]Brekhman II. Ginseng. Leningrad: State Publishing House of Medical Literature MEDGIZ; 1957: 182.
  10. [71]Brekhman II. Eleutherococcus. Leningrad: Nauka; 1968: 188.
  11. [72]Saratikov AS, Krasnov EA. Rhodiola rosea (Golden root). Tomsk: Tomsk State University Publishing House; 2004: 292.
  12. [74]Bogatova RI, Shlykova LV, Salnitsky VP, Wikman G. Evaluation of the effect of a single dose of a phytoadaptogen on the working capacity of human subjects during prolonged isolation. Aerosp Environ Med. 1997; 31: 51‐ 54. 9424198
  13. [76]Hovhannisyan AS, Panossian AG. Wikman G. ADAPT‐232 and ADAPT‐S for stress‐induced fatigue and recovery of trained and elite athletes: a randomized, controlled trial. J Athl Enhancement. 2015; 4: 4.
  14. [83]Brekhman II. Valeology—The science of health. Moscow: Physical education and sport:; 1990: 208.
  15. [89]Pharmacopoeia of the People's Republic of China 2015. 1st ed., HM He, L Cui, (Eds). Beijing: China Medical Science Press. 2017.
  16. [90]Ginseng Radix. WHO monographs on selected medicinal plants. World Health Organization; 1999; 1: 168‐ 182.
  17. [92]Kuchta K. 3 Fachleute—3 Behandlungsstrategien: Lebensverlängerndes Phytotherapeutikum weiterhin gesucht! Zkm. 2015; 6: 40‐ 41.
  18. [110]Avicenna. Canon of Medical Science. Tashkent: Tashkent. Publ, Usb. Acad. Sci.; book 1, 1954; book 2, 1956; book 3, vol. 1, 1958, vol. 2, 1959, vol. 4, 1960 (russ.)
  19. [111]Amirdovlat Amasiatsi. Unnecessary for the Ignorant or a Dictionary of Medicinal Substances. Vienna: Mkhitaristov; 1926: 766.
  20. [112]Amirdovlat Amasiatsi. Unnecessary for the ignorant. Moscow: Science; 1990: 880.
  21. [113]Ganalanian AT. Armenian Legends. Yerevan: Acad. Sci. Arm. SSR; 1969: 530.
  22. [115]Jensen D. Uber zwei einheimische Giftpflanzen. Eine kritisch‐literarische und experimentelle Studie. Inaugural Dissertation zur Erlangung der Doktorwurde der hohen medi zinischen Fakulrat der Universitat zu Rostock, Rostock; 1914:57.
  23. [116]Wilson CO, Jones TE. American Drug Index. Philadelphia, PA and Montreal: J. B. Lippincott Company; 1959: 671.
  24. [117]The Extra Pharmacopoeia. (Martindale). v. 1. 24th ed. London: Pharmaceutical Press; 1958: 1362.
  25. [119]Hager H. Hagers Handbuch der pharmazeutischen Praxis für Apotheker, Arzneimittelhersteller, Ärzte und Medizinalbeamte. Chemikalien und Drogen (AM‐CH). Berlin: Springer; 1972: 911.
  26. [121]Daems WE. Ita Wegman und das erste Mistelpraparat Iscar zur Krebsbehandlung In: Leroi REd., Misteltherapie. Eine Antwort auf die Herausforderung Krebs. Die Pioniertat Rudolf Steiners und Ita Wegmans. Stuttgart: Verlag Freies Geistesleben; 1987: 35‐ 44.
  27. [137]Canguilhem G. Essai sur quelques problèmes concernant le normal et le pathologique. 1943. In: Fawcett CR, Cohen RS, trans. The Normal and the Pathological. New York: Zone Books; 1991.
  28. [153]Duraisami R, Mohite VA, Kasbe AJ. Anti stress, adaptogenic activity of standardized dried fruit extract of Aegle marmelos against diverse stressors. Asian J Pharm Clin Res. 2010; 3: 1‐ 3.
  29. [163]Padma P, Chansauria JPN, Khosa RL, Ray AK. Effect of Annona muricata and Polyalthia cerasoides on brain neurotransmitters and enzyme monoamine oxidase following cold immobilization stress. J Nat Remedies. 2001; 1: 144‐ 146.
  30. [166]Mamedov N. Adaptogenic, geriatric, stimulant and antidepressant plants of Russian Far East. J Cell Mol Biology. 2005; 4: 71‐ 75.
  31. [169]Garg R, Gupta VB. Adaptogenic activity of milk and aqueous decoction of Asparagus racemosus Willd. in acute and chronic stress paradigms in mice. J Cell Tissue Res. 2010; 10: 2281‐ 2286.
  32. [182]Pal P, Bose S. Phytopharmacological and phytochemical review of Butea monosperma. Int J Res Pharm Biomed Sci. 2011; 2: 1374‐ 1388.
  33. [188]Koppula S, Kopalli SR, Sreemantula S. Adaptogenic and nootropic activities of aqueous extracts of Carum Carvi L. (Caraway) fruit: an experimental study in Wistar rats. Aust J Medical Herbal. 2009; 21: 72‐ 78.
  34. [191]Gopalkrishna B, Akki KS, Patil SH, Hukkeri VI. Preliminary phytochemical investigation and in vivo antistress activity of Safed musli (Chlorophytum Borivillianum L.). Indian Drugs. 2006; 43: 878‐ 880.
  35. [197]Shilova IV, Suslov NI, Krasnov EA. Adaptogenic and nootropic properties of the thick extract from the aerial part of Atragene sibirica L. Plant Resources. 2001; 37: 78‐ 88.
  36. [214]Pareek S, Shikov AN, Pozharitskaya ON, et al. Indian Gooseberry (Emblica officinalis Gaertn) In: Yahia EM, ed. Fruit and Vegetable Phytochemicals: Chemistry and Human Health. Wiley‐Blackwell; 2017: 1077‐ 1105.
  37. [220]Singh A. Review of ethnomedicinal uses and pharmacology of Evolvulus alsinoides L. Ethnobot Leaflets. 2010; 12: 734‐ 740.
  38. [221]Kothiyal P, Ratan P. Antistress effect of Fagopyrum esculentum in rats subjected to forced swimming endurance test. Pharmacologyonline. 2011; 3: 290‐ 296.
  39. [231]Natraj GR, Nanjappaiah HM, Hugar S. Evaluation of adaptogenic potential of Hibiscus cannabinus in acute stress induced mice. Pharmacologyonline. 2011; 2: 508‐ 513.
  40. [245]Saraf MN, Sanaye MM, Mengi SA. Antifatigue effect of Murraya koenigii. Pharmacologyonline. 2011; 2: 1025‐ 1037.
  41. [246]Koul S, Chaudhary A. Radical scavenging and antistress activity of Mussaenda frondosa roots (Rubiaceae). Pharmacologyonline. 2011; 1: 1091‐ 1097.
  42. [249]Roshan S, Khan A, Taznee B, Ali S. To study the effect of Nigella sativa on various biochemical parameters on stress induced in albino rats. Int J Pharm Pharm Sci. 2010; 2: 185‐ 189.
  43. [252]Anju L. Adaptogenic and anti‐stress activity of Ocimum sanctum in mice. Res J Pharm Biol Chem Sci. 2011; 2: 670‐ 678.
  44. [265]Giri M, Rao PM, Jayaveera KN. Evaluation of adaptogenic activity of Prunella vulgaris. Int J Pharm Sci Res. 2011; 8: 62‐ 65.
  45. [273]Yunuskhodjaev AN, Iskandarova SF, Kurmukov A, Saidov SA. Study of adaptogenic properties and chronic toxicity of extract of Rhodiola heterodonta. Eur J Natural History. 2014; 2: 35‐ 38.
  46. [304]Pawar VS, Hugar S. A current status of adaptogens: natural remedy to stress. Asian Pacific J Tropical Disease. 2012; 2: S480‐ S490.
  47. [306]Pawar VS, Shivakumar H. Antistress activity of Trigonella foenum graecum L. seeds using swimming endurance and cold stress in rodents. Indian Drugs. 2011a; 48: 56‐ 61.
  48. [311]Singh N, Nath R, Lata A, Singh SP, Kohli RP, Bhargava KP. Withania somnifera (Ashwagandha), a rejuvenating herbal drug which enhances survival during stress (an adaptogen). Pharm Biol. 1982; 20: 29‐ 35.
  49. [352]Panossian A, Wagner H. Adaptogens. A review of their history, biological activity, and clinical benefits. HerbalGram. 2011; 90: 52‐ 63.
  50. [369]Panossian A, Wikman G. Evidence based efficacy and effectiveness of Rhodiola SHR‐5 extract in treating stress‐ and age‐associated disorders In: Cuerrier A, Ampong‐Nyarko K, eds. Rhodiola rosea, Series: Traditional Herbal Medicines for Modern Times. Boca‐Raton London New‐York: CRC Press, Taylor & Francis Group; 2014: 203‐ 221.
  51. [412]Kupin VI, Polevaya ES, Sorokin AM. Increased immunologic reactivity of lymphocytes in oncologic patients treated with Eleutherococcus extract. In: New Data on Eleutherococcus: Proceedings of the 2nd International Symposium on Eleutherococcus, Moscow 1984, Vladivostok; 1986: 216‐ 220.
  52. [413]Zykov MP, Protasova SF. Prospects of immunostimulating vaccination against influenza including the use of Eleutherococcus and other preparations of plant origin. In: Proceedings of New Data on Eleutherococcus, Moscow: 118‐122.
  53. [414]Wacker, A, Eichler, A, Lodemann, E The molecular mechanism of virus inhibition by Eleutherococcus. In: New Data on Eleutherococcus: Proceedings of the 2nd International Symposium on Eleutherococcusow 1984, Vladivostok, 1986: 13‐ 15.
  54. [415]Wacker A, Eilmes HG. Virushemmung mit Eleutherokokk Fluid‐Extrakt. Erfahrungsheilkunde. 1978; 27: 346‐ 351.
  55. [416]Wacker A. Über die Interferon induzierende und immunstimulierende Wirkung von Eleutherococcus. Erfahrungsheilkunde. 1983; 32: 339‐ 343.
  56. [420]ESCOP Monographs, 2nd ed. Supplement 2009. Eleutherococci radix—Eleutheroccus. European Scientific Cooperative on Phytotherapy, editor. Thieme, Stuttgart; 2009; 110‐ 120.
  57. [474]Brekhman II. On antitoxic action of Eleutherococcus. Moscow: Meditsina; 1982: 37.
  58. [477]Sakharova TA, Revazova YA, Barenboim GM. The effect of Eleutherococcus extract on the induction of recessive lethal mutations by cyclophosphane and N‐nitrosomorpholine in Drosophila. Khim Farm Zh. 1985; 19: 539‐ 540.
  59. [484]Stukov AN. Combined action of Eleutherococcus senticosus and sarcolysin on lymphosarcoma LIO‐I in mice. Vopr Oncol. 1966; 12: 57‐ 60.
  60. [581]EMEA/HMPC/102655/2007. Reflection paper on the adaptogenic concept. Committee on Herbal Medicinal Products; 2008: 1‐ 6.
  61. [584]Barenboim GM, Sterlina AG, Bebyakova NV, Ribokas AA, Fuks BB. Investigation of the pharmacokinetics and mechanism of action of Eleutherococcus glycosides. VIII. Investigation of natural killer activation by Eleutherococcus extract. Khim Farm Zh. 1986; 20: 914‐ 917.
  62. [585]Bezdetko GN, German AV, Shevchenko VP, et al. Study of the pharmacokinetics and action mechanism of Eleutherococcus glycosides. I. Incorporation of tritium into eleutherosides B, Kinetics of its accumulation and excretion from the body of animal. Khim Farm Z. 1981; 15: 28‐ 33.
  63. [586]German AV, Bezdetko GN, Mitrokhin YI, Chivkov GN, Shevchenko VP, Barenboim GM. Dardymov. Study of the pharmacokinetics and mechanism of Eleutherococcus glycosides. II. Distribution of eleutheroside in organs and subcellular fraction. Khim Farm Zh. 1982; 16: 26‐ 30.
  64. [597]Panossian A, Hovhannisyan A, Abrahamyan H, Wikman G. Pharmacokinetics of active constituents of Rhodiola rosea SHR‐5 extract In: Gupta VK, ed. Comprehensive Bioactive Natural Products. Vol. 2: Efficacy, Safety & Clinical Evaluation I. Houston: Studium Press; 2010: 307‐ 329.
  65. [606]Kosman VM, Karlina MV, Pozharitskaya ON, et al. Pharmacokinetics of lignans from Schisandra chinensis. Rev Clin Pharmacol Drug Ther. 2015; 13: 3‐ 21.
  66. [608]Wang Z, Wu Q, Meng Y, et al. Determination and pharmacokinetic study of two triterpenoid saponins in rat plasma after oral administration of the extract of Aralia elata leaves by UHPLC‐ESI‐MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2015; 985: 164‐ 171. 25687802
  67. [609]Lin W, Ma J, Yu S. Pharmacokinetics of araloside X in rats and tissue distribution in mice by UPLC‐MS/MS. Latin American J Pharmacy. 2019; 38: 1505‐ 1509.
  68. [621]Kim DH. Gut microbiota‐mediated pharmacokinetics of ginseng saponins. J Ginseng Res. 2018; 42: 255‐ 263. 29983606 PMC6026358

Authors
Panossian, A. G., Efferth, T., Shikov, A. N., Pozharitskaya, O. N., Kuchta, K., Mukherjee, P. K., Banerjee, S., Heinrich, M., Wu, W., Guo, D., & Wagner, H.
Affiliations
  • Phytomed AB Vaxtorp Sweden
  • Johannes Gutenberg University Mainz (DE)
  • Saint - Petersburg State Chemical Pharmaceutical Academy (RU)
  • Russian Academy of Sciences (RU)
  • Universitätsmedizin Göttingen (DE)
  • Jadavpur University (IN)
  • University of London (GB)
  • Chinese Academy of Sciences (CN)
  • Ludwig-Maximilians-Universität München (DE)
Corresponding author
Panossian, Alexander G.
ORCID
Venue
Medicinal Research Reviews
Publisher
Wiley
Published
2020-10-25
Volume
41
Issue
1
Pages
630-703
ISSN
  • 0198-6325 (ISSN-L)
  • 1098-1128
DOI
10.1002/med.21743
PMC
PMC7756641
OpenAlex
W3093753665
Cited by
347
References
572
Citations by year
2026: 50 · 2025: 58 · 2024: 54 · 2023: 79 · 2022: 62 · 2021: 37 · 2020: 6
FWCI
4.40
Type
journal article
Language
en
Open access
Licence
Locations
  • Medicinal Research Reviews (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Medicinal Plants and Bioactive Compounds
  • Health Sciences › Medicine › Complementary and alternative medicine › Phytochemicals and Medicinal Plants
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ginseng Biological Effects and Applications
Keywords
adaptogens, adaptogenic herbs, stress response, age-related diseases, neuroendocrine-immune network, biphasic dose-response, network pharmacology, systems pharmacology, herbal medicine
MeSH terms
Aging, Humans, Plant Extracts, Signal Transduction

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review