Vol. 36 (2026): Volumen 36
Artículos de revisión

Adaptogens: nature, function, and main representatives

PDF (Spanish)
  • Jorge Alejandro Sosa Gutiérrez,
  • Cristo Omar Puente Valenzuela,
  • Rolando Adair Facio Campos,
  • Edgar Héctor Olivas Calderón
Jorge Alejandro Sosa Gutiérrez Universidad Juárez del Estado de Durango Facultad de Ciencias Químicas Gómez Palacio
Cristo Omar Puente Valenzuela Universidad Juárez del Estado de Durango Facultad de Ciencias Biológicas Gómez Palacio
Rolando Adair Facio Campos Universidad Juárez del Estado de Durango Facultad de Ciencias Químicas Gómez Palacio
Edgar Héctor Olivas Calderón Universidad Juárez del Estado de Durango Facultad de Ciencias Químicas Gómez Palacio

Published 2026-03-25

Copyright (c) 2026 Jorge Alejandro Sosa Gutiérrez, Cristo Omar Puente Valenzuela, Rolando Adair Facio Campos, Edgar Héctor Olivas Calderón

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

How to Cite

Sosa Gutiérrez, J. A., Puente Valenzuela, C. O., Facio Campos, R. A., & Olivas Calderón, E. H. (2026). Adaptogens: nature, function, and main representatives. Acta Universitaria, 36, 1-34. https://doi.org/10.15174/au.2026.4743

Abstract

Adaptogens are natural compounds, primarily of plant origin, that have attracted growing scientific interest due to their ability to enhance the body's nonspecific resistance to physical, mental, and environmental stress. They act by modulating the hypothalamic-pituitary-adrenal (HPA) axis and other neuroendocrine systems, promoting homeostasis without altering normal physiological functions. Recent research has documented beneficial effects of adaptogens such as Panax ginseng, Rhodiola rosea, and Withania somnifera in reducing stress, fatigue, and mood disorders, as well as in improving physical and cognitive performance. Despite empirical support from preclinical and clinical studies, challenges remain regarding the standardization of extracts, specific molecular mechanisms, and large-scale clinical validation. This paper reviews the most recent evidence on major adaptogens, their mechanisms of action, therapeutic applications, and future perspectives.

PDF (Spanish)

References

  1. Abdelwahed, M. T., Hegazy, M. A., & Mohamed, E. H. (2023). Major biochemical constituents of Withania somnifera (ashwagandha) extract: a review of chemical analysis. Reviews in Analytical Chemistry, 42(1). https://doi.org/10.1515/REVAC-2022-0055
  2. Afewerky, H. K., Ayodeji, A. E., Tiamiyu, B. B., Orege, J. I., Okeke, E. S., Oyejobi, A. O., Ndip, P., & Adeyemi, S. B. (2021). Critical review of the Withania somnifera (L.) Dunal: ethnobotany, pharmacological efficacy, and commercialization significance in Africa. Bulletin of the National Research Centre, 45(1), 1–16. https://doi.org/10.1186/S42269-021-00635-6
  3. Agapouda, A., Grimm, A., Lejri, I., & Eckert, A. (2022). Rhodiola rosea extract counteracts stress in an adaptogenic response curve manner via elimination of ROS and induction of neurite outgrowth. Oxidative Medicine and Cellular Longevity, 2022(1), 5647599. https://doi.org/10.1155/2022/5647599
  4. Alanazi, H. H., & Elfaki, E. (2023). The immunomodulatory role of withania somnifera (L.) dunal in inflammatory diseases. Frontiers in Pharmacology, 14, 1084757. https://doi.org/10.3389/FPHAR.2023.1084757
  5. Al-Eisa, R. A. (2025). A review on selected pharmacological and phytochemical activities of Ashwagandha (Withania somnifera). Egyptian Journal of Veterinary Sciences, 0(0), 1–23. https://doi.org/10.21608/EJVS.2025.311925.2328
  6. Aminifard, T., Razavi, B. M., & Hosseinzadeh, H. (2021). The effects of ginseng on the metabolic syndrome: an updated review. Food Science & Nutrition, 9(9), 5293-5311. https://doi.org/10.1002/FSN3.2475
  7. An, L., Yu, Y., He, L., Xiao, X., & Li, P. (2024). Ginsenoside Rb1 deters cell proliferation, induces apoptosis, alleviates oxidative stress, and antimetastasis in oral squamous carcinoma cells. Applied Biochemistry and Biotechnology, 196(11), 7642–7656. https://doi.org/10.1007/S12010-024-04880-Z
  8. Anghelescu, I. G., Edwards, D., Seifritz, E., & Kasper, S. (2018). Stress management and the role of Rhodiola rosea: a review. International Journal of Psychiatry in Clinical Practice, 22(4), 242–252. https://doi.org/10.1080/13651501.2017.1417442
  9. Arshad, M. T., Maqsood, S., Ikram, A., & Abdullahi, M. A. (2025). Functional, nutraceutical, and health-endorsing perspectives of Ashwagandha. EFood, 6(3), e70061. https://doi.org/10.1002/EFD2.70061
  10. Arumugam, V., Vijayakumar, V., Balakrishnan, A., Bhandari, R. B., Boopalan, D., Ponnurangam, R., Sankaralingam, V., & Kuppusamy, M. (2024). Effects of Ashwagandha (Withania Somnifera) on stress and anxiety: a systematic review and meta-analysis. EXPLORE, 20(6), 103062. https://doi.org/10.1016/J.EXPLORE.2024.103062
  11. Atteeq, M. (2022). Evaluating anticancer properties of Withaferin A—a potent phytochemical. Frontiers in Pharmacology, 13, 975320. https://doi.org/10.3389/FPHAR.2022.975320
  12. Awang, D., La, Z., Baima, K., Xie, H., Wang, L., Liu, X., Wang, Y., Shi, Y., Zhao, Y., & Gongga, L. (2025). Salidroside from Rhodiola Rosea L. attenuates high-altitude hypoxic myocardial injury via modulating oxidative stress and Akt/Gsk-3β signaling. https://doi.org/10.2139/SSRN.5384513
  13. Bai, R., Zhao, Z., Han, X., Shang, M., Liu, G., Xu, F., & Cai, S. (2025). Therapeutic potential of ginsenosides in anthracycline-induced cardiotoxicity. Molecules, 30(12), 2527. https://doi.org/10.3390/MOLECULES30122527
  14. Basarrate, S., Monzel, A. S., Smith, J. L. M., Marsland, A. L., Trumpff, C., & Picard, M. (2024). Glucocorticoid and adrenergic receptor distribution across human organs and tissues: a map for stress transduction. Psychosomatic Medicine, 86(2), 89–98. https://doi.org/10.1097/PSY.0000000000001275
  15. Bashir, A., Nabi, M., Tabassum, N., Afzal, S., & Ayoub, M. (2023). An updated review on phytochemistry and molecular targets of Withania somnifera (L.) Dunal (Ashwagandha). Frontiers in Pharmacology, 14, 1049334. https://doi.org/10.3389/FPHAR.2023.1049334
  16. Basudkar, V., Gujrati, G., Ajgaonkar, S., Gandhi, M., Mehta, D., & Nair, S. (2024). Emerging vistas for the nutraceutical Withania somnifera in inflammaging. Pharmaceuticals, 17(5), 597. https://doi.org/10.3390/PH17050597
  17. Bernatoniene, J., Jakstas, V., & Kopustinskiene, D. M. (2023). Phenolic compounds of Rhodiola rosea L. as the potential alternative therapy in the treatment of chronic diseases. International Journal of Molecular Sciences, 24(15), 12293. https://doi.org/10.3390/IJMS241512293
  18. Bian, S., Liu, M., Yang, S., Lu, S., Wang, S., Bai, X., Zhao, D., & Wang, J. (2021). 20(S)-Ginsenoside Rh2-induced apoptosis and protective autophagy in cervical cancer cells by inhibiting AMPK/mTOR pathway. Bioscience, Biotechnology, and Biochemistry, 86(1), 92–103. https://doi.org/10.1093/BBB/ZBAB189
  19. Bian, X. B., Yu, P. C., Yang, X. H., Han, L., Wang, Q. Y., Zhang, L., Zhang, L. X., & Sun, X. (2023). The effect of ginsenosides on liver injury in preclinical studies: a systematic review and meta-analysis. Frontiers in Pharmacology, 14, 1184774. https://doi.org/10.3389/FPHAR.2023.1184774
  20. Bilia, A. R., & Bergonzi, M. C. (2019). The G115 standardized ginseng extract: an example for safety, efficacy, and quality of an herbal medicine. Journal of Ginseng Research, 44(2), 179-193. https://doi.org/10.1016/J.JGR.2019.06.003
  21. Cai, J., Huang, K., Han, S., Chen, R., Li, Z., Chen, Y., Chen, B., Li, S., Xinhua, L., & Yao, H. (2022). A comprehensive system review of pharmacological effects and relative mechanisms of Ginsenoside Re: recent advances and future perspectives. Phytomedicine, 102, 154119. https://doi.org/10.1016/J.PHYMED.2022.154119
  22. Che, W., Wojitas, L., Shan, C., & Lopchuk, J. M. (2024). Divergent synthesis of complex withanolides enabled by a scalable route and late-stage functionalization. Science Advances, 10(26), eadp9375. https://doi.org/10.1126/SCIADV.ADP9375
  23. Cheah, K. L., Norhayati, M. N., Yaacob, L. H., & Rahman, R. A. (2021). Effect of Ashwagandha (Withania somnifera) extract on sleep: a systematic review and meta-analysis. PLOS ONE, 16(9), e0257843. https://doi.org/10.1371/JOURNAL.PONE.0257843
  24. Chen, P., Liu, M., Xiao, H., Luo, T., Ling, H., Chen, X., Li, Z., Xu, S., Li, Z., & Deng, J. (2025). Ginsenoside Re ameliorates cardiac hypertrophy by regulating CaSR-mediated signaling pathway. International Journal of Drug Discovery and Pharmacology, 4(1), 2504000183. https://doi.org/10.53941/IJDDP.2025.100006
  25. Chen, Q., Yang, C., Wang, D., Luo, S., & Ma, S. (2025). Rhodiola rosea stimulates brain microcirculation in rats with hypoxic brain injury at high altitude. Pakistan Journal of Zoology, 57(4), 1883–1888. https://doi.org/10.17582/JOURNAL.PJZ/20240206130209
  26. Chen, W., Balan, P., & Popovich, D. G. (2020). Comparison of ginsenoside components of various tissues of New Zealand forest-grown Asian ginseng (Panax Ginseng) and American ginseng (Panax Quinquefolium L.). Biomolecules, 10(3), 372. https://doi.org/10.3390/BIOM10030372
  27. Chen, Y., Tang, M., Yuan, S., Fu, S., Li, Y., Li, Y., Wang, Q., Cao, Y., Liu, L., & Zhang, Q. (2022). Rhodiola rosea: a therapeutic candidate on cardiovascular diseases. Oxidative Medicine and Cellular Longevity, 2022(1), 1348795. https://doi.org/10.1155/2022/1348795
  28. Chopra, P., Chhillar, H., Kim, Y. J., Jo, I. H., Kim, S. T., & Gupta, R. (2023). Phytochemistry of ginsenosides: recent advancements and emerging roles. Critical Reviews in Food Science and Nutrition, 63(5), 613–640. https://doi.org/10.1080/10408398.2021.1952159
  29. Chu, L. L., Montecillo, J. A. V., & Bae, H. (2020). Recent advances in the metabolic engineering of yeasts for ginsenoside biosynthesis. Frontiers in Bioengineering and Biotechnology, 8, 515823. https://doi.org/10.3389/FBIOE.2020.00139
  30. Concerto, C., Infortuna, C., Muscatello, M. R. A., Bruno, A., Zoccali, R., Chusid, E., Aguglia, E., & Battaglia, F. (2018). Exploring the effect of adaptogenic Rhodiola Rosea extract on neuroplasticity in humans. Complementary Therapies in Medicine, 41, 141–146. https://doi.org/10.1016/j.ctim.2018.09.013
  31. Cong, L., Ma, J., Zhang, Y., Zhou, Y., Cong, X., & Hao, M. (2023). Effect of anti-skin disorders of ginsenosides- A systematic review. Journal of Ginseng Research, 47(5), 605–614. https://doi.org/10.1016/J.JGR.2023.04.005
  32. Cui, J., Shan, R., Cao, Y., Zhou, Y., Liu, C., & Fan, Y. (2021). Protective effects of ginsenoside Rg2 against memory impairment and neuronal death induced by Aβ25-35 in rats. Journal of Ethnopharmacology, 266, 113466. https://doi.org/10.1016/J.JEP.2020.113466
  33. Dai, Y. L., Qiao, M. D., Yu, P., Zheng, F., Yue, H., & Liu, S. Y. (2020). Comparing eight types of ginsenosides in ginseng of different plant ages and regions using RRLC-Q-TOF MS/MS. Journal of Ginseng Research, 44(2), 205–214. https://doi.org/10.1016/J.JGR.2017.11.001
  34. Dar, N. J., Bhat, J. A., Satti, N. K., Sharma, P. R., Hamid, A., & Ahmad, M. (2017). Withanone, an active constituent from Withania somnifera, affords protection against NMDA-induced excitotoxicity in neuron-like cells. Molecular Neurobiology, 54(7), 5061–5073. https://doi.org/10.1007/S12035-016-0044-7
  35. De Oliveira, B., de Oliveira, A. R., Miola, V. F. B., Gissoni, L. M., Spilla, C. S. G., & Barbalho, S. M. (2022). Panax ginseng and aging related disorders: a systematic review. Experimental Gerontology, 161, 111731. https://doi.org/10.1016/J.EXGER.2022.111731
  36. Della Porta, M., Maier, J. A., & Cazzola, R. (2023). Effects of Withania somnifera on cortisol levels in stressed human subjects: a systematic review. Nutrients, 15(24), 5015. https://doi.org/10.3390/NU15245015
  37. Deshpande, A., Irani, N., Balkrishnan, R., & Benny, I. R. (2020). A randomized, double blind, placebo controlled study to evaluate the effects of ashwagandha (Withania somnifera) extract on sleep quality in healthy adults. Sleep Medicine, 72, 28–36. https://doi.org/10.1016/J.SLEEP.2020.03.012
  38. Dimpfel, W., Schombert, L., & Panossian, A. G. (2018). Assessing the quality and potential efficacy of commercial extracts of Rhodiola rosea L. by analyzing the salidroside and rosavin content and the electrophysiological activity in hippocampal long-term potentiation, a synaptic model of memory. Frontiers in Pharmacology, 9, 425. https://doi.org/10.3389/FPHAR.2018.00425
  39. Dinel, A. L., Guinobert, I., Lucas, C., Blondeau, C., Bardot, V., Ripoche, I., Berthomier, L., Pallet, V., Layé, S., & Joffre, C. (2019). Reduction of acute mild stress corticosterone response and changes in stress-responsive gene expression in male Balb/c mice after repeated administration of a Rhodiola rosea L. root extract. Food Science & Nutrition, 7(11), 3827–3841. https://doi.org/10.1002/FSN3.1249
  40. Dipankar, S. P., Dani, M. M., Anirudhan, R., Tripathi, D., Mishra, C., & Devi, S. H. (2025). Pharmacological insights into Ashwagandha (Withania somnifera): a review of its immunomodulatory and neuroprotective properties. Cureus, 17(8), e89856. https://doi.org/10.7759/CUREUS.89856
  41. Dongre, S., Langade, D., & Bhattacharyya, S. (2015). Efficacy and safety of Ashwagandha (Withania somnifera) root extract in improving sexual function in women: a pilot study. BioMed Research International, 2015(1), 284154. https://doi.org/10.1155/2015/284154
  42. Dormal, V., Jonniaux, L., Buchet, M., Simar, L., Copine, S., & Deldicque, L. (2025). Effect of hydroponically grown red panax ginseng on perceived stress level, emotional processing, and cognitive functions in moderately stressed adults: a randomized, double-blind, placebo-controlled study. Nutrients, 17(6), 955. https://doi.org/10.3390/NU17060955
  43. Dutta, R., Khalil, R., Green, R., Mohapatra, S. S., & Mohapatra, S. (2019). Withania Somnifera (Ashwagandha) and Withaferin A: potential in integrative oncology. International Journal of Molecular Sciences, 20(21), 5310. https://doi.org/10.3390/IJMS20215310
  44. Edwards, D., Heufelder, A., & Zimmermann, A. (2012). Therapeutic effects and safety of Rhodiola rosea extract WS® 1375 in subjects with life-stress symptoms--results of an open-label study. Phytotherapy Research, 26(8), 1220–1225. https://doi.org/10.1002/PTR.3712
  45. Er, B., Ozmen, B., Sahin, E., Orhan, C., Sahin, N., Morde, A. A., Padigaru, M., & Sahin, K. (2025). A novel Ashwagandha (Withania somnifera) formulation mitigates sleep deprivation-induced cognitive impairment and oxidative stress in a rat model. Biomolecules, 15(5), 710. https://doi.org/10.3390/BIOM15050710
  46. Esmaealzadeh, N., Iranpanah, A., Sarris, J., & Rahimi, R. (2022). A literature review of the studies concerning selected plant-derived adaptogens and their general function in body with a focus on animal studies. Phytomedicine, 105, 154354. https://doi.org/10.1016/j.phymed.2022.154354
  47. Fan, S., Zhang, Z., Su, H., Xu, P., Qi, H., Zhao, D., & Li, X. (2020). Panax ginseng clinical trials: current status and future perspectives. Biomedicine & Pharmacotherapy, 132, 110832. https://doi.org/10.1016/J.BIOPHA.2020.110832
  48. Fan, W., Fan, L., Wang, Z., Mei, Y., Liu, L., Li, L., Yang, L., & Wang, Z. (2024). Rare ginsenosides: a unique perspective of ginseng research. Journal of Advanced Research, 66, 303-328. https://doi.org/10.1016/J.JARE.2024.01.003
  49. Fang, F., Chen, X., Huang, T., Lue, L. F., Luddy, J. S., & Yan, S. S. (2011). Multi-faced neuroprotective effects of Ginsenoside Rg1 in an Alzheimer mouse model. Biochimica et Biophysica Acta, 1822(2), 286.
  50. https://doi.org/10.1016/J.BBADIS.2011.10.004
  51. Fang, X., Zhou, X., Wang, Y., Zhang, W., Wu, H., Xu, L., Sun, M., & Xiao, H. (2024). Determining the genetic basis of ginsenosides variation during ginseng domestication by evolutionary transcriptomics. Industrial Crops and Products, 212, 118369. https://doi.org/10.1016/J.INDCROP.2024.118369
  52. Fanibunda, S. E., Kukkemane, K., Ghai, U., Kolthur-Seetharam, U., Hingorani, L., Vaidya, A. D. B., & Vaidya, V. A. (2025). Withania somnifera regulates mitochondrial biogenesis and energetics in rat cortical neurons: role of BDNF and SIRT1. Molecular Neurobiology, 62(8), 10277–10295. https://doi.org/10.1007/S12035-025-04920-7
  53. Feng, H., Xue, M., Deng, H., Cheng, S., Hu, Y., & Zhou, C. (2022). Ginsenoside and its therapeutic potential for cognitive impairment. Biomolecules, 12(9), 1310. https://doi.org/10.3390/BIOM12091310
  54. Ferreira, J. F., Ferreira, R. M., Maia, F., Fernandes, L. G., Leão, C., & Pimenta, N. (2025). Biopsychological effects of Ashwagandha (Withania somnifera) in athletes and healthy individuals: a systematic review. Muscles, 4(3), 24. https://doi.org/10.3390/MUSCLES4030024
  55. Fu, H., Zhang, Y., An, Q., Wang, D., You, S., Zhao, D., Zhang, J., Wang, C., & Li, M. (2022). Anti-photoaging effect of Rhodiola rosea fermented by Lactobacillus plantarum on UVA-damaged fibroblasts. Nutrients, 14(11), 2324. https://doi.org/10.3390/NU14112324
  56. Gao, L., Wu, C., Liao, Y., Zhang, S., & Zhao, J. (2021). Herba Rhodiolae alleviates depression via the BDNF/TrkB-GSK-3β signaling pathway. Annals of Translational Medicine, 9(24), 1758–1758. https://doi.org/10.21037/ATM-21-5849
  57. Gaurav, H., Yadav, D., Maurya, A., Yadav, H., Yadav, R., Shukla, A. C., Sharma, M., Gupta, V. K., & Palazon, J. (2023). Biodiversity, biochemical profiling, and pharmaco-commercial applications of Withania somnifera: a review. Molecules, 28(3), 1208. https://doi.org/10.3390/MOLECULES28031208
  58. Gębalski, J., Małkowska, M., Graczyk, F., Słomka, A., Piskorska, E., Gawenda-Kempczyńska, D., Kondrzycka-Dąda, A., Bogucka-Kocka, A., Strzemski, M., Sowa, I., Wójciak, M., Grzyb, S., Krolik, K., Ptaszyńska, A. A., & Załuski, D. (2023). Phenolic compounds and antioxidant and anti-enzymatic activities of selected adaptogenic plants from South America, Asia, and Africa. Molecules, 28(16), 6004. https://doi.org/10.3390/MOLECULES28166004
  59. Geng, B., Zhao, M., Wang, J., Zhong, T., Kang, C., Wang, Z., Ma, X., & Xia, T. (2024). Ginsenoside Rh2 promotes cell apoptosis in T-cell acute lymphocytic leukaemia by MAPK and PI3K/AKT signalling pathways. Natural Product Research. https://doi.org/10.1080/14786419.2024.2440537
  60. Gerontakos, S. E., Wardle, J., & Casteleijn, D. (2020). A critical review to identify the domains used to measure the effect and outcome of adaptogenic herbal medicines. Advances in Integrative Medicine, 6(1), 133-134. https://doi.org/10.1016/j.aimed.2019.03.389
  61. Girme, A., Saste, G., Pawar, S., Balasubramaniam, A. K., Musande, K., Darji, B., Satti, N. K., Verma, M. K., Anand, R., Singh, R., Vishwakarma, R. A., & Hingorani, L. (2020). Investigating 11 withanosides and withanolides by UHPLC–PDA and mass fragmentation studies from Ashwagandha (Withania somnifera). ACS Omega, 5(43), 27933–27943. https://doi.org/10.1021/ACSOMEGA.0C03266
  62. Gokdemir, G. S., Seker, U., Baksi, N., Baylan, M., Demirtaş, B., & Gokdemir, M. T. (2026). Antidepressant-like effects of Ashwagandha (Withania Somnifera) on chronic unpredictable mild stress-induced depression in adolescent rats. Psychopharmacology, 243, 117–132. https://doi.org/10.1007/S00213-025-06844-5
  63. Gómez, A., Fernandez-Lazaro, D., Adams, D. P., Monserdà-Vilaró, A., & Fernandez-Lazaro, C. I. (2023). Effects of Withania somnifera (Ashwagandha) on hematological and biochemical markers, hormonal behavior, and oxidant response in healthy adults: a systematic review. Current Nutrition Reports, 12(3), 465–477. https://doi.org/10.1007/S13668-023-00481-0
  64. Gong, L., Yin, J., Zhang, Y., Huang, R., Lou, Y., Jiang, H., Sun, L., Jia, J., & Zeng, X. (2022). Neuroprotective mechanisms of ginsenoside Rb1 in central nervous system diseases. Frontiers in Pharmacology, 13, 914352. https://doi.org/10.3389/FPHAR.2022.914352
  65. Gopukumar, K., Thanawala, S., Somepalli, V., Rao, T. S. S., Thamatam, V. B., & Chauhan, S. (2021). Efficacy and safety of Ashwagandha root extract on cognitive functions in healthy, stressed adults: a randomized, double-blind, placebo-controlled study. Evidence-Based Complementary and Alternative Medicine, 2021(1), 8254344. https://doi.org/10.1155/2021/8254344
  66. Guo, S., & Rezaei, M. J. (2024). The benefits of ashwagandha (Withania somnifera) supplements on brain function and sports performance. Sports and Exercise Nutrition, 11. https://doi.org/10.3389/FNUT.2024.1439294
  67. Gupta, M., & Kaur, G. (2016). Aqueous extract from the Withania somnifera leaves as a potential anti-neuroinflammatory agent: a mechanistic study. Journal of Neuroinflammation, 13(193). https://doi.org/10.1186/S12974-016-0650-3
  68. Gurav, S., Wanjari, M., Bhole, R., Raut, N., Prasad, S., Saoji, S., Chikhale, R., Khanal, P., Pant, A., Ayyanar, M., & Gurav, N. (2023). Ethnological validation of Ashwagandha (Withania somnifera L. Dunal) ghrita as ‘Vajikarana Rasayana’: In-silico, in-vitro and in-vivo approach. Journal of Ethnopharmacology, 304, 116064. https://doi.org/10.1016/J.JEP.2022.116064
  69. Haber, M., Czachor, A., Kula, P., Juśkiewicz, A., Grelewicz, O., Kucy, N., Servaas, E., Kotula, A., & Siemiątkowski, R. (2024). Ashwagandha as an adaptogen: its influence on sleep patterns, stress response, and anxiety in modern life. Journal of Education, Health and Sport, 68, 55327. https://doi.org/10.12775/JEHS.2024.68.55327
  70. Han, D., Zhao, Z., Mao, T., Gao, M., Yang, X., & Gao, Y. (2024). Ginsenoside Rg1: a neuroprotective natural dammarane‐type triterpenoid saponin with anti‐depressive properties. CNS Neuroscience & Therapeutics, 30(12), e70150. https://doi.org/10.1111/CNS.70150
  71. Han, J. Y., Kim, H. J., Kwon, Y. S., & Choi, Y. E. (2011). The Cyt P450 enzyme CYP716A47 catalyzes the formation of protopanaxadiol from dammarenediol-II during ginsenoside biosynthesis in Panax ginseng. Plant and Cell Physiology, 52(12), 2062–2073. https://doi.org/10.1093/PCP/PCR150
  72. Hasanyn, R. F., Batawi, A. H., Al-Thepyani, M. A., Tash, R., Almuhammadi, A., Alsabban, A. H., & Alghamdi, B. S. (2025). Ashwagandha root extract mitigates fibromyalgia-like symptoms via neurochemical and histological modulation in mice. Cells, 14(18), 1478. https://doi.org/10.3390/CELLS14181478
  73. Hernández-Santana, A., Pérez-López, V., Zubeldia, J. M., & Jiménez-Del-Rio, M. (2014). A Rhodiola rosea root extract protects skeletal muscle cells against chemically induced oxidative stress by modulating heat shock protein 70 (HSP70) expression. Phytotherapy Research, 28(4), 623–628. https://doi.org/10.1002/PTR.5046
  74. Hou, J., Cui, C., Kim, S., Sung, C., & Choi, C. (2018). Ginsenoside F1 suppresses astrocytic senescence-associated secretory phenotype. Chemico-Biological Interactions, 283, 75–83.
  75. https://doi.org/10.1016/J.CBI.2018.02.002
  76. Hou, J., Yun, Y., Jeon, B., Baek, J., & Kim, S. (2023). Ginsenoside F1-mediated telomere preservation delays cellular senescence. International Journal of Molecular Sciences, 24(18), 14241.
  77. https://doi.org/10.3390/IJMS241814241
  78. Hou, M., Wang, R., Zhao, S., & Wang, Z. (2021). Ginsenosides in Panax genus and their biosynthesis. Acta Pharmaceutica Sinica B, 11(7), 1813–1834. https://doi.org/10.1016/J.APSB.2020.12.017
  79. Hou, W., Wang, Y., Zheng, P., & Cui, R. (2020). Effects of ginseng on neurological disorders. Frontiers in Cellular Neuroscience, 14, 510085. https://doi.org/10.3389/FNCEL.2020.00055
  80. Hu, Y., Cho, J. Y., & Kim, M. Y. (2025). Pharmacokinetics and pharmacological activities of protopanaxatriol. Journal of Ginseng Research, 49(6), 613-621. https://doi.org/10.1016/J.JGR.2025.07.004
  81. Huang, C., Li, P., Yang, X., Niu, T., Zhao, S., Yang, L., Wang, R., & Wang, Z. (2023). Integrated transcriptome and proteome analyses reveal candidate genes for ginsenoside biosynthesis in Panax japonicus C. A. Meyer. Frontiers in Plant Science, 13, 1106145. https://doi.org/10.3389/FPLS.2022.1106145
  82. Huang, X., Daneshi, M., Falahatzadeh, M., & Rounagh, M. (2025). The effect of ginseng supplementation and health outcomes: a GRADE-assessed systematic review and meta-analysis of randomized controlled trials. Journal of Functional Foods, 129, 106879. https://doi.org/10.1016/J.JFF.2025.106879
  83. Hung, S. K., Perry, R., & Ernst, E. (2011). The effectiveness and efficacy of Rhodiola rosea L.: a systematic review of randomized clinical trials. Phytomedicine, 18(4), 235–244. https://doi.org/10.1016/j.phymed.2010.08.014
  84. Hyun, S. H., Bhilare, K. D., In, G., Park, C. K., & Kim, J. H. (2021). Effects of Panax ginseng and ginsenosides on oxidative stress and cardiovascular diseases: pharmacological and therapeutic roles. Journal of Ginseng Research, 46(1), 33-38. https://doi.org/10.1016/J.JGR.2021.07.007
  85. Irfan, M., Kwak, Y. S., Han, C. K., Hyun, S. H., & Rhee, M. H. (2020). Adaptogenic effects of Panax ginseng on modulation of cardiovascular functions. Journal of Ginseng Research, 44(4), 538–543. https://doi.org/10.1016/J.JGR.2020.03.001
  86. Jang, W. Y., Hwang, J. Y., & Cho, J. Y. (2023). Ginsenosides from Panax ginseng as key modulators of NF-κB signaling are powerful anti-inflammatory and anticancer agents. International Journal of Molecular Sciences, 24(7), 6119. https://doi.org/10.3390/IJMS24076119
  87. Jayawardena, R., Weerasinghe, K., & Sooriyaarachchi, P. (2025). The effect of Ashwagandha (Withania somnifera) on sports performance: a systematic review and meta-analysis. Spor Hekimliği Dergisi, 60(2), 064–073. https://doi.org/10.47447/TJSM.0862
  88. Jeong, J. S., Kim, J. W., Kim, J. H., Kim, C. Y., Chung, E. H., Boo, S. Y., Giorgi, M., Ko, J. W., & Kim, T. W. (2025). Pharmacokinetic variability of 20(S)-protopanaxadiol-type ginsenosides Rb1, rd, and compound K from Korean red ginseng in experimental rodents. Scientific Reports, 15(1), 28072. https://doi.org/10.1038/S41598-025-13873-9
  89. Jo, H., Jang, D., Park, S. K., Lee, M. G., Cha, B., Park, C., Shin, Y. S., Park, H., Baek, J., Heo, H., Brito, S., Hwan, H. G., Chae, S., Yan, S., Lee, C., Min, C. K., & Bin, B. H. (2021). Ginsenoside 20(S)-protopanaxadiol induces cell death in human endometrial cancer cells via apoptosis. Journal of Ginseng Research, 45(1), 126–133. https://doi.org/10.1016/j.jgr.2020.02.002
  90. Jówko, E., Sadowski, J., Długołęcka, B., Gierczuk, D., Opaszowski, B., & Cieśliński, I. (2018). Effects of Rhodiola rosea supplementation on mental performance, physical capacity, and oxidative stress biomarkers in healthy men. Journal of Sport and Health Science, 7(4), 473–480. https://doi.org/10.1016/J.JSHS.2016.05.005
  91. Jurcău, R., Lambinet, M., Jurcău, I., & Rusu, L. D. (2019). A PubMed evaluation of the Rhodiola rosea adaptogen. Health, Sports & Rehabilitation Medicine, 20(4), 174–178. https://doi.org/10.26659/PM3.2019.20.4.174
  92. Jurcău, R. N., Jurcău, I. M., Lambinet, M., Colceriu, N. A., Trif, F. G., & Kwak, D. H. (2025). Modulatory role of Rhodiola Rosea in anxiety and stress: a PubMed approach. BULETIN ŞTIINŢIFIC SERIA A Fascicula Pedagogie-Psihologie-Metodică, 25, 211–218. https://doi.org/10.37193/BS-PPM.25.19
  93. Kang, O. J., & Kim, J. S. (2016). Comparison of ginsenoside contents in different parts of Korean ginseng (Panax ginseng C.A. Meyer). Preventive Nutrition and Food Science, 21(4), 389–392. https://doi.org/10.3746/PNF.2016.21.4.389
  94. Kang, S., & Min, H. (2012). Ginseng, the “Immunity Boost”: the effects of Panax ginseng on immune system. Journal of Ginseng Research, 36(4), 354-368. https://doi.org/10.5142/JGR.2012.36.4.354
  95. Kanyaiya, M., Digambar, S. P., Arora, S., Kapila, S., & Singh, R. R. B. (2014). In vivo, effect of herb (Withania somnifera) on immunomodulatory and antioxidative potential of milk in mice. Food and Agricultural Immunology, 25(3), 443–452. https://doi.org/10.1080/09540105.2013.837032
  96. Karimi, M., Barjasteh, A. H., Shariatzadeh, M., Taha, S. R., Fazlollahpour-naghibi, A., Rezaei, P., Aghaei, M., Ghanbari, M., & Pourhanifeh, M. H. (2025). Ginsenosides and gastrointestinal cancers: a novel therapeutic strategy in cancer therapy. Pathology - Research and Practice, 272, 156078. https://doi.org/10.1016/J.PRP.2025.156078
  97. Kasprzyk, P. G., Tremaine, L., Fahmi, O. A., & Weng, J. K. (2023). In Vitro evaluation of the potential for drug interactions by salidroside. Nutrients, 15(17), 3723. https://doi.org/10.3390/NU15173723
  98. Kaur, J., Seshadri, S., Golla, K. H., & Sampara, P. (2022). Efficacy and safety of standardized Ashwagandha (Withania somnifera) root extract on reducing stress and anxiety in domestic dogs: a randomized controlled trial. Journal of Veterinary Behavior, 51, 8–15. https://doi.org/10.1016/J.JVEB.2022.03.002
  99. Khalil, H. M. A., Eliwa, H. A., El-Shiekh, R. A., Al-Mokaddem, A. K., Hassan, M., Tawfek, A. M., & El-Maadawy, W. H. (2021). Ashwagandha (Withania somnifera) root extract attenuates hepatic and cognitive deficits in thioacetamide-induced rat model of hepatic encephalopathy via induction of Nrf2/HO-1 and mitigation of NF-κB/MAPK signaling pathways. Journal of Ethnopharmacology, 277, 114141. https://doi.org/10.1016/J.JEP.2021.114141
  100. Khan, M. A., Ahmed, R. S., Chandra, N., Arora, V. K., & Ali, A. (2019). In vivo, extract from Withania somnifera root ameliorates arthritis via regulation of key immune mediators of inflammation in experimental model of arthritis. Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, 18(1), 55. https://doi.org/10.2174/1871523017666181116092934
  101. Kim, D., Kim, M., Raña, G. S., & Han, J. (2018). Seasonal variation and possible biosynthetic pathway of ginsenosides in Korean ginseng Panax ginseng Meyer. Molecules, 23(7), 1824. https://doi.org/10.3390/MOLECULES23071824
  102. Kim, H., Choi, H. S., Han, K., Sim, W., Suh, H. J., & Ahn, Y. (2025). Ashwagandha (Withania somnifera (L.) dunal) root extract containing withanolide a alleviates depression-like behavior in mice by enhancing the brain-derived neurotrophic factor pathway under unexpected chronic mild stress. Journal of Ethnopharmacology, 340, 119224. https://doi.org/10.1016/J.JEP.2024.119224
  103. Kim, H. W., Kim, D. H., Ryu, B., Chung, Y. J., Lee, K., Kim, Y. C., Lee, J. W., Kim, D. H., Jang, W., Cho, W., Shim, H., Sung, S. H., Yang, T. J., & Kang, K. B. (2024). Mass spectrometry-based ginsenoside profiling: recent applications, limitations, and perspectives. Journal of Ginseng Research, 48(2), 149-162. https://doi.org/10.1016/J.JGR.2024.01.004
  104. Kim, J. H., Yi, Y. S., Kim, M. Y., & Cho, J. Y. (2017). Role of ginsenosides, the main active components of Panax ginseng, in inflammatory responses and diseases. Journal of Ginseng Research, 41(4), 435–443. https://doi.org/10.1016/J.JGR.2016.08.004
  105. Kim, J. K., Choi, M. S., Park, H. S., Kee, K. H., Kim, D. H., & Yoo, H. H. (2023). Pharmacokinetic profiling of ginsenosides, Rb1, Rd, and Rg3, in mice with antibiotic-induced gut microbiota alterations: implications for variability in the therapeutic efficacy of red ginseng extracts. Foods, 12(23), 43-42. https://doi.org/10.3390/FOODS12234342
  106. Kim, Y. J., Zhang, D., & Yang, D. C. (2015). Biosynthesis and biotechnological production of ginsenosides. Biotechnology Advances, 33(6), 717–735. https://doi.org/10.1016/J.BIOTECHADV.2015.03.001
  107. Kim, Y. S., Woo, J. Y., Han, C. K., & Chang, I. M. (2015). Safety analysis of Panax Ginseng in randomized clinical trials: a systematic review. Medicines, 2(2), 106-126. https://doi.org/10.3390/MEDICINES2020106
  108. Krishnaraju, A. V., Somepalli, V., Thanawala, S., & Shah, R. (2023). Efficacy and anti-inflammatory activity of ashwagandha sustained-release formulation on depression and anxiety induced by chronic unpredictable stress: in vivo and in vitro studies. Journal of Experimental Pharmacology, 15, 291. https://doi.org/10.2147/JEP.S407906
  109. Kumar, P., Sharma, R., & Garg, N. (2022). Withania somnifera - a magic plant targeting multiple pathways in cancer related inflammation. Phytomedicine, 101, 154137. https://doi.org/10.1016/j.phymed.2022.154137
  110. Kumar, S., Mathew, S. O., Aharwal, R. P., Tulli, H. S., Mohan, C. D., Sethi, G., Ahn, K. S., Webber, K., Sandhu, S. S., & Bishayee, A. (2023). Withaferin A: a pleiotropic anticancer agent from the Indian medicinal plant Withania somnifera (L.) Dunal. Pharmaceuticals, 16(2), 160. https://doi.org/10.3390/PH16020160
  111. Langade, D., Kanchi, S., Salve, J., Debnath, K., & Ambegaokar, D. (2019). Efficacy and safety of Ashwagandha (Withania somnifera) root extract in insomnia and anxiety: a double-blind, randomized, placebo-controlled study. Cureus, 11(9). https://doi.org/10.7759/CUREUS.5797
  112. Le, M. H., Ahn, Y. H., Lee, H. J., & Kim, Y. J. (2024). Stem-and-leaf of new hydroponically-cultured ginseng cultivar K-1: a sustainable and innovative resource of ginsenosides for anti-inflammatory agents. Journal of Ginseng Research, 48(6), 616–626. https://doi.org/10.1016/J.JGR.2024.07.001
  113. Lee, D. H., Ahn, J., Jang, Y. J., Seo, H. D., Ha, T. Y., Kim, M. J., Huh, Y. H., & Jung, C. H. (2020). Withania somnifera extract enhances energy expenditure via improving mitochondrial function in adipose tissue and skeletal muscle. Nutrients, 12(2), 431. https://doi.org/10.3390/NU12020431
  114. Lee, K., Lee, D., Kim, J. Y., Shim, J. J., Bae, J. W., & Lee, J. H. (2025). Attenuation effect of Withania somnifera extract on restraint stress-induced anxiety-like behavior and hippocampal alterations in mice. International Journal of Molecular Sciences, 26(15), 7317. https://doi.org/10.3390/IJMS26157317
  115. Lee, N. H., Yoo, S. R., Kim, H. G., Cho, J. H., & Son, C. G. (2012). Safety and tolerability of panax ginseng root extract: a randomized, placebo-controlled, clinical trial in healthy Korean volunteers. Journal of Alternative and Complementary Medicine, 18(11), 1061. https://doi.org/10.1089/ACM.2011.0591
  116. Lee, R., Kim, J. H., Kim, W. W., Hwang, S. H., Choi, S. H., Kim, J. H., Cho, I. H., Kim, M., & Nah, S. Y. (2024). Emerging evidence that ginseng components improve cognition in subjective memory impairment, mild cognitive impairment, and early Alzheimer’s disease dementia. Journal of Ginseng Research, 48(3), 245–252. https://doi.org/10.1016/J.JGR.2024.02.002
  117. Lee, S., & Rhee, D. K. (2017). Effects of ginseng on stress-related depression, anxiety, and the hypothalamic–pituitary–adrenal axis. Journal of Ginseng Research, 41(4), 589–594. https://doi.org/10.1016/J.JGR.2017.01.010
  118. Lee, Y. M., Yoon, H., Park, H. M., Song, B. C., & Yeum, K. J. (2017). Implications of red Panax ginseng in oxidative stress associated chronic diseases. Journal of Ginseng Research, 41(2), 113–119. https://doi.org/10.1016/J.JGR.2016.03.003
  119. Leonard, M., Dickerson, B., Estes, L., Gonzalez, D. E., Jenkins, V., Johnson, S., Xing, D., Yoo, C., Ko, J., Purpura, M., Jäger, R., Faries, M., Kephart, W., Sowinski, R., Rasmussen, C. J., & Kreider, R. B. (2024). Acute and repeated ashwagandha supplementation improves markers of cognitive function and mood. Nutrients, 16(12), 1813. https://doi.org/10.3390/NU16121813
  120. Lerose, V., Ponticelli, M., Benedetto, N., Carlucci, V., Lela, L., Tzvetkov, N. T., & Milella, L. (2024). Withania somnifera (L.) Dunal, a potential source of phytochemicals for treating neurodegenerative diseases: a systematic review. Plants, 13(6), 771. https://doi.org/10.3390/PLANTS13060771
  121. Li, F., Lv, C., Li, Q., Wang, J., Song, D., Liu, P., Zhang, D., & Lu, J. (2017). Chemical and bioactive comparison of flowers of Panax ginseng Meyer, Panax quinquefolius L., and Panax notoginseng Burk. Journal of Ginseng Research, 41(4), 487–495. https://doi.org/10.1016/J.JGR.2016.08.008
  122. Li, J., Huang, Q., Yao, Y., Ji, P., Mingyao, E., Chen, J., Zhang, Z., Qi, H., Liu, J., Chen, Z., Zhao, D., Zhou, L., & Li, X. (2022). Biotransformation, pharmacokinetics, and pharmacological activities of ginsenoside Rd against multiple diseases. Frontiers in Pharmacology, 13, 909363. https://doi.org/10.3389/FPHAR.2022.909363
  123. Li, X., Cheng, X., Liao, B., Xu, J., Han, X., Zhang, J., Lin, Z., & Hu, L. (2021). Spatial protein expression of Panax ginseng by in-depth proteomic analysis for ginsenoside biosynthesis and transportation. Journal of Ginseng Research, 45(1), 58–65. https://doi.org/10.1016/J.JGR.2020.01.009
  124. Li, Y., Pham, V., Bui, M., Song, L., Wu, C., Walia, A., Uchio, E., Smith-Liu, F., & Zi, X. (2017). Rhodiola rosea L.: an herb with anti-stress, anti-aging, and immunostimulating properties for cancer chemoprevention. Current Pharmacology Reports, 3(6), 384. https://doi.org/10.1007/S40495-017-0106-1
  125. Liang, C. J. W., Woerdenbag, H. J., Ekhart, C., Vitalone, A., & van Hunsel, F. P. A. M. (2025). Safety considerations for natural products with adaptogenic and immunomodulating activities. Pharmaceuticals, 18(8), 1208. https://doi.org/10.3390/PH18081208
  126. Liang, J., Tang, X., Wan, S., Guo, J., Zhao, P., & Lu, L. (2023). Structure modification of ginsenoside Rh2 and cytostatic activity on cancer cells. ACS Omega, 8(19), 17245–17253. https://doi.org/10.1021/ACSOMEGA.3C01665
  127. Liao, L. Y., He, Y. F., Li, L., Meng, H., Dong, Y. M., Yi, F., & Xiao, P. G. (2018). A preliminary review of studies on adaptogens: comparison of their bioactivity in TCM with that of ginseng-like herbs used worldwide. Chinese Medicine, 13(57). https://doi.org/10.1186/S13020-018-0214-9
  128. Limanaqi, F., Biagioni, F., Busceti, C. L., Polzella, M., Fabrizi, C., & Fornai, F. (2020). Potential antidepressant effects of Scutellaria baicalensis, Hericium erinaceus and Rhodiola rosea. Antioxidants, 9(3), 234. https://doi.org/10.3390/ANTIOX9030234
  129. Liu, S., Chen, W., Zhao, Y., Zong, Y., Li, J., & He, Z. (2023). Research progress on effects of ginsenoside Rg2 and Rh1 on nervous system and related mechanisms. Molecules, 28(23) 7935.
  130. https://doi.org/10.3390/MOLECULES28237935
  131. Liu, W., Zhang, S. X., Ai, B., Pan, H. F., Zhang, D., Jiang, Y., Hu, L. H., Sun, L. L., Chen, Z. S., & Lin, L. Z. (2021). Ginsenoside Rg3 promotes cell growth through activation of mTORC1. Frontiers in Cell and Developmental Biology, 9, 730309. https://doi.org/10.3389/FCELL.2021.730309
  132. Liu, Y., Ju, Y., Wang, Y., Cui, X., Sun, Y., Hu, P., & Chen, Y. (2025). Ginsenoside in the treatment of type 2 diabetes and its complications: a promising traditional Chinese medicine. Frontiers in Pharmacology, 16, 1593780. https://doi.org/10.3389/FPHAR.2025.1593780
  133. Liu, Y., Zong, X., Huang, J., Guan, Y., Li, Y., Du, T., Liu, K., Kang, X., Dou, C., Sun, X., Wu, R., Wen, L., & Zhang, Y. (2019). Ginsenoside Rb1 regulates prefrontal cortical GABAergic transmission in MPTP-treated mice. Aging, 11(14), 5008–5034. https://doi.org/10.18632/AGING.102095
  134. Lopresti, A. L., Smith, S. J., & Drummond, P. D. (2022). Modulation of the hypothalamic-pituitary-adrenal (HPA) axis by plants and phytonutrients: a systematic review of human trials. Nutritional Neuroscience, 25(8), 1704–1730. https://doi.org/10.1080/1028415X.2021.1892253
  135. Lopresti, A. L., Smith, S. J., Malvi, H., & Kodgule, R. (2019). An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: a randomized, double-blind, placebo-controlled study. Medicine, 98(37), e17186. https://doi.org/10.1097/MD.0000000000017186
  136. Lu, Y., Deng, B., Xu, L., Liu, H., Song, Y., & Lin, F. (2022). Effects of Rhodiola Rosea supplementation on exercise and sport: a systematic review. Frontiers in Nutrition, 9. https://doi.org/10.3389/FNUT.2022.856287
  137. Lu, Z., Mao, T., Chen, K., Chai, L., Dai, Y., & Liu, K. (2023). Ginsenoside Rc: a potential intervention agent for metabolic syndrome. Journal of Pharmaceutical Analysis, 13(12), 1375–1387. https://doi.org/10.1016/J.JPHA.2023.08.013
  138. Ma, G. P., Zheng, Q., Xu, M. B., Zhou, X. L., Lu, L., Li, Z. X., & Zheng, G. Q. (2018). Rhodiola rosea L. improves learning and memory function: preclinical evidence and possible mechanisms. Frontiers in Pharmacology, 9, 1415. https://doi.org/10.3389/FPHAR.2018.01415
  139. Maccioni, R., Cottiglia, F., Maccioni, E., Talani, G., Sanna, E., Bassareo, V., Kasture, S. B., & Acquas, E. (2021). The biologically active compound of Withania somnifera (L.) Dunal, docosanyl ferulate, is endowed with potent anxiolytic properties but devoid of typical benzodiazepine-like side effects. Journal of Psychopharmacology (Oxford, England), 35(10), 1277–1284. https://doi.org/10.1177/02698811211008588
  140. Maher, S., Choudhary, M. I., Saleem, F., Rasheed, S., Waheed, I., Halim, S. A., Azeem, M., Abdullah, I. Bin, Froeyen, M., Mirza, M. U., & Ahmad, S. (2020). Isolation of antidiabetic Withanolides from Withania coagulans Dunal and their in vitro and in silico validation. Biology, 9(8), 197. https://doi.org/10.3390/BIOLOGY9080197
  141. Marciniak, A., Nemeczek, S., Walczak, K., Walczak, P., Merkisz, K., Grzybowski, J., Grzywna, N., Jaskuła, K., & Orłowski, W. (2023). Adaptogens-use, history and future. Quality in Sport, 9(1), 19–28. https://doi.org/10.12775/QS.2023.09.01.002
  142. Mariage, P. A., Hovhannisyan, A., & Panossian, A. G. (2020). Efficacy of panax ginseng meyer herbal preparation hrg80 in preventing and mitigating stress-induced failure of cognitive functions in healthy subjects: a pilot, randomized, double-blind, placebo-controlled crossover trial. Pharmaceuticals, 13(4) 57. https://doi.org/10.3390/PH13040057
  143. Masi, F., Chianese, G., Hofstetter, R. K., Cavallaro, A. L., Riva, A., Werz, O., & Taglialatela-Scafati, O. (2023). Phytochemical profile and anti-inflammatory activity of a commercially available Rhodiola rosea root extract. Fitoterapia, 166, 105439. https://doi.org/10.1016/J.FITOTE.2023.105439
  144. McEwen, B. S. (2017). Neurobiological and systemic effects of chronic stress. Chronic Stress (Thousand Oaks, Calif.), 1. https://doi.org/10.1177/2470547017692328
  145. Mehta, J. P., Kagal, U. A., & Biradar, P. R. (2025). Effect of Withania somnifera on expression of selected genes in hippocampus of male wistar rats subjected to chronic unpredictable mild stress. International Journal of Applied and Basic Medical Research, 15(1), 25-31. https://doi.org/10.4103/IJABMR.IJABMR_330_24
  146. Michels, B., Franke, K., Weiglein, A., Sultani, H., Gerber, B., & Wessjohann, L. A. (2020). Rewarding compounds identified from the medicinal plant Rhodiola rosea. The Journal of Experimental Biology, 223(16), jeb223982. https://doi.org/10.1242/JEB.223982
  147. Mikulska, P., Malinowska, M., Ignacyk, M., Szustowski, P., Nowak, J., Pesta, K., Szeląg, M., Szklanny, D., Judasz, E., Kaczmarek, G., Ejiohuo, O. P., Paczkowska-Walendowska, M., Gościniak, A., & Cielecka-Piontek, J. (2023). Ashwagandha (Withania somnifera)—Current research on the health-promoting activities: a narrative review. Pharmaceutics, 15(4), 1057. https://doi.org/10.3390/PHARMACEUTICS15041057
  148. Mishra, D. N., & Kumar, M. (2024). Shoden promotes relief from stress and anxiety: a randomized, double-blind, placebo-controlled study on healthy subjects with high stress levels. Heliyon, 10(17), e36885. https://doi.org/10.1016/J.HELIYON.2024.E36885
  149. Mishra, S. K., Venkatachalapathy, B. A., & Khanli, H. M. (2017). Safety and efficacy of Ashwagandha (Withania somnifera). En G. Brahmachari (ed.), Neuroprotective natural products: clinical aspects and mode of action
  150. (pp. 313–319). Wiley. https://doi.org/10.1002/9783527803781
  151. Mohanan, P., Subramaniyam, S., Mathiyalagan, R., & Yang, D. C. (2018). Molecular signaling of ginsenosides Rb1, Rg1, and Rg3 and their mode of actions. Journal of Ginseng Research, 42(2), 123–132.
  152. https://doi.org/10.1016/J.JGR.2017.01.008
  153. Mohanan, P., Yang, T. J., & Song, Y. H. (2023). Genes and regulatory mechanisms for ginsenoside biosynthesis. Journal of Plant Biology, 66(1), 87–97. https://doi.org/10.1007/S12374-023-09384-7
  154. Mohsin, M. M., Hanif, M. A., Ayub, M. A., & Dharmadasa, R. M. (2023). Ginseng. En Medicinal Plants of South Asia: Novel Sources for Drug Discovery (pp. 331–340). Elseviere. https://doi.org/10.1016/B978-0-08-102659-5.00025-2
  155. Morshed, M. N., Ahn, J. C., Mathiyalagan, R., Rupa, E. J., Akter, R., Karim, M. R., Jung, D. H., Yang, D. U., Yang, D. C., & Jung, S. K. (2023). Antioxidant activity of panax ginseng to regulate ROS in various chronic diseases. Applied Sciences (Switzerland), 13(5), 2893. https://doi.org/10.3390/APP13052893
  156. Mukherjee, P. K., Banerjee, S., Biswas, S., Das, B., Kar, A., & Katiyar, C. K. (2021). Withania somnifera (L.) Dunal - Modern perspectives of an ancient Rasayana from Ayurveda. Journal of Ethnopharmacology, 264, 113157. https://doi.org/10.1016/j.jep.2020.113157
  157. Murthy, S. V., Fathima, S. N., & Mote, R. (2022). Hydroalcoholic extract of Ashwagandha improves sleep by modulating GABA/Histamine receptors and EEG slow-wave pattern in in vitro - in vivo experimental models. Preventive Nutrition and Food Science, 27(1), 108-120. https://doi.org/10.3746/PNF.2022.27.1.108
  158. Nan, F., Sun, G., Xie, W., Ye, T., Sun, X., Zhou, P., Dong, X., Sun, J., Sun, X., & Zhang, M. (2019). Ginsenoside Rb1 mitigates oxidative stress and apoptosis induced by methylglyoxal in SH-SY5Y cells via the PI3K/Akt pathway. Molecular and Cellular Probes, 48, 101469. https://doi.org/10.1016/J.MCP.2019.101469
  159. Narayanan, A. K., & Nagegowda, D. A. (2024). Biosynthesis of the triterpenoid withanolides in Withania somnifera. Current Opinion in Plant Biology, 81, 102576. https://doi.org/10.1016/J.PBI.2024.102576
  160. Noushad, S., Ahmed, S., Ansari, B., Mustafa, U. H., Saleem, Y., & Hazrat, H. (2021). Physiological biomarkers of chronic stress: a systematic review. International Journal of Health Sciences, 15(5), 46. https://pmc.ncbi.nlm.nih.gov/articles/PMC8434839/
  161. Obulesu, M. (2022). Effect of plant extracts against Alzheimer’s disease. Plant Extracts in Neurodegenerative Diseases, 1–15. https://doi.org/10.1016/B978-0-323-95762-5.00001-1
  162. Ozeer, F. Z., Nagandran, S., Wu, Y. S., Wong, L. S., Stephen, A., Lee, M. F., Kijsomporn, J., Guad, R. Mac, Batumalaie, K., Oyewusi, H. A., Verma, A., Yadav, E., Afzal, S., Sekar, M., Subramaniyan, V., Fuloria, N. K., Fuloria, S., & Sarker, M. M. R. (2024). A comprehensive review of phytochemicals of Withania somnifera (L.) Dunal (Solanaceae) as antiviral therapeutics. Discover Applied Sciences, 6(187), 1–20. https://doi.org/10.1007/S42452-024-05845-X
  163. Paik, D. J., & Lee, C. H. (2015). Review of cases of patient risk associated with ginseng abuse and misuse. Journal of Ginseng Research, 39(2), 89-93. https://doi.org/10.1016/J.JGR.2014.11.005
  164. Paik, S., Song, G. Y., & Jo, E. K. (2023). Ginsenosides for therapeutically targeting inflammation through modulation of oxidative stress. International Immunopharmacology, 121, 110461. https://doi.org/10.1016/J.INTIMP.2023.110461
  165. Panossian, A., & Brendler, T. (2020). The role of adaptogens in prophylaxis and treatment of viral respiratory infections. Pharmaceuticals, 13(9), 236. https://doi.org/10.3390/PH13090236
  166. Panossian, A., & Efferth, T. (2022). Network pharmacology of adaptogens in the assessment of their pleiotropic therapeutic activity. Pharmaceuticals, 15(9), 1051. https://doi.org/10.3390/PH15091051
  167. Panossian, A. G. (2013). Adaptogens in mental and behavioral disorders. Psychiatric Clinics of North America, 36(1), 49–64. https://doi.org/10.1016/J.PSC.2012.12.005
  168. Panossian, A., & Lemerond, T. (2025). Two sides of the same coin for health: adaptogenic botanicals as nutraceuticals for nutrition and pharmaceuticals in medicine. Pharmaceuticals, 18(9). https://doi.org/10.3390/PH18091346
  169. Park, K. C., Jin, H., Zheng, R., Kim, S., Lee, S. E., Kim, B. H., & Yim, S. V. (2019). Cognition enhancing effect of panax ginseng in Korean volunteers with mild cognitive impairment: a randomized, double-blind, placebo-controlled clinical trial. Translational and Clinical Pharmacology, 27(3), 92. https://doi.org/10.12793/TCP.2019.27.3.92
  170. Park, S. H., Chung, S., Chung, M. Y., Choi, H. K., Hwang, J. T., & Park, J. H. (2022). Effects of Panax ginseng on hyperglycemia, hypertension, and hyperlipidemia: a systematic review and meta-analysis. Journal of Ginseng Research, 46(2), 188–205. https://doi.org/10.1016/J.JGR.2021.10.002
  171. Park, S. K., Hyun, S. H., In, G., Park, C. K., Kwak, Y. S., Jang, Y. J., Kim, B., Kim, J. H., & Han, C. K. (2021). The antioxidant activities of Korean Red Ginseng (Panax ginseng) and ginsenosides: a systemic review through in vivo and clinical trials. Journal of Ginseng Research, 45(1), 41–47. https://doi.org/10.1016/J.JGR.2020.09.006
  172. Patnaik, N., & Patnaik, N. (2015). Role of Brahmi and Ashwagandha in anti-ageing. Journal of Biosciences and Medicines, 3(10), 102–104. https://doi.org/10.4236/JBM.2015.310014
  173. Peng, Z., Wu, W. W., & Yi, P. (2021). The efficacy of ginsenoside Rg3 combined with first-line chemotherapy in the treatment of advanced non-small cell lung cancer in China: a systematic review and meta-analysis of randomized clinical trials. Frontiers in Pharmacology, 11, 630825. https://doi.org/10.3389/FPHAR.2020.630825
  174. Piecuch, D., Sobota, W., Zwoliński, M., Piskorz, P., Hańczyk, E., Zemsta, K., & Kulesza, B. (2024). Ashwagandha (Withania somnifera) en la terapia del cáncer: actividades anticancerígenas y sus mecanismos. Calidad en el Deporte, 32, 56016. https://doi.org/10.12775/QS.2024.32.56016
  175. Pratte, M. A., Nanavati, K. B., Young, V., & Morley, C. P. (2014). An alternative treatment for anxiety: a systematic review of human trial results reported for the Ayurvedic Herb Ashwagandha (Withania somnifera). Journal of Alternative and Complementary Medicine, 20(12), 901–908. https://doi.org/10.1089/acm.2014.0177
  176. Priyanka, G., Anil Kumar, B., Lakshman, M., Manvitha, V., & Kala Kumar, B. (2020). Adaptogenic and immunomodulatory activity of Ashwagandha root extract: an experimental study in an equine model. Frontiers in Veterinary Science, 7, 541112. https://doi.org/10.3389/FVETS.2020.541112
  177. Pu, J., Yang, J., Xu, B., Zhang, Y., Zhang, W., Yang, D., Sun-Waterhouse, D., & Li, D. (2025). Targeting cancer epigenetics with PPD-type ginsenosides: a systematic review of mechanisms and therapeutic potential. Phytomedicine, 148, 157352. https://doi.org/10.1016/J.PHYMED.2025.157352
  178. Pushpakaran, A. M. K., Singh, J., Rasane, P., Kaur, S., Kaur, J., Kaur, J., Kumar, M., & Assouguem, A. (2025). Immunomodulatory effect of ashwagandha (Withania somnifera L. Dunal) and its impact on COVID-19. Foods and Raw Materials, 13(1), 46–57. https://doi.org/10.21603/2308-4057-2025-1-622
  179. Radad, K., Moldzio, R., & Rausch, W. D. (2010). Ginsenosides and their CNS targets. CNS Neuroscience & Therapeutics, 17(6), 761-768. https://doi.org/10.1111/J.1755-5949.2010.00208.X
  180. Rakha, A., Ramzan, Z., Umar, N., Rasheed, H., Fatima, A., Ahmed, Z., Kieliszek, M., & Aadil, R. M. (2023). The role of Ashwagandha in metabolic syndrome: a review of traditional knowledge and recent research findings. Journal of Biological Regulators and Homeostatic Agents, 37(10), 5091–5103. https://doi.org/10.23812/J.BIOL.REGUL.HOMEOST.AGENTS.20233710.494
  181. Ramapalaniappan, A., Loganathan, V., Morde, A., Padigaru, M., Patni, P., Joshua, L., & Thomas, J. V. (2025). Superior bioavailability of a novel 1.5% ashwagandha formulation (ZenrootTM): a randomized, double-blind, single-dose, comparative, oral bioavailability study in healthy adults. Advances in Therapy, 42(10), 4964-4976. https://doi.org/10.1007/S12325-025-03292-7
  182. Ramona, J., Ioana, J., Nicolae-Alexandru, C., Ovidiu, M., & Răzvan-Titus, P. (2024). Relationship between Ginseng, hypothalamic pituitary adrenal axis and Cortisol: a PubMed approach. Health, Sports & Rehabilitation Medicine, 25(1), 37–40. https://doi.org/10.26659/PM3.2024.25.1.37
  183. Ran, X., Dou, D., Chen, H., & Ren, G. (2022). The correlations of adverse effect and tonifying effect of ginseng medicines. Journal of Ethnopharmacology, 291, 115113. https://doi.org/10.1016/j.jep.2022.115113
  184. Ratan, Z. A., Haidere, M. F., Hong, Y. H., Park, S. H., Lee, J. O., Lee, J., & Cho, J. Y. (2020). Pharmacological potential of ginseng and its major component ginsenosides. Journal of Ginseng Research, 45(2), 199-210. https://doi.org/10.1016/J.JGR.2020.02.004
  185. Ratan, Z. A., Youn, S. H., Kwak, Y. S., Han, C. K., Haidere, M. F., Kim, J. K., Min, H., Jung, Y. J., Hosseinzadeh, H., Hyun, S. H., & Cho, J. Y. (2020). Adaptogenic effects of Panax ginseng on modulation of immune functions. Journal of Ginseng Research, 45(1), 32-40. https://doi.org/10.1016/J.JGR.2020.09.004
  186. Razgonova, M. P., Veselov, V. V., Zakharenko, A. M., Golokhvast, K. S., Nosyrev, A. E., Cravotto, G., Tsatsakis, A., & Spandidos, D. A. (2019). Panax ginseng components and the pathogenesis of Alzheimer’s disease. Molecular Medicine Reports, 19(4), 2975-2998. https://doi.org/10.3892/MMR.2019.9972
  187. Rodthongdee, K., Watanapa, W. B., Ruamyod, K., Semprasert, N., Nambundit, P., Kooptiwut, S., & Boontaveekul, L. (2025). Ginsenoside Re increases human coronary artery endothelial SKCa current and nitric oxide release via glucocorticoid receptor-PI3K-Akt/PKB pathway. Journal of Ginseng Research. https://doi.org/10.1016/J.JGR.2025.04.008
  188. Ross, S. M. (2014). Rhodiola rosea (SHR-5), Part I: a proprietary root extract of Rhodiola rosea is found to be effective in the treatment of stress-related fatigue. Holistic Nursing Practice, 28(2), 149–154.
  189. https://doi.org/10.1097/HNP.0000000000000014
  190. Ross, S. M. (2023). The clinical efficacy of Rhodiola rosea L. in managing stress-induced conditions. Holistic Nursing Practice, 37(4), 233–235. https://doi.org/10.1097/HNP.0000000000000597
  191. Ryu, H. J., Jung, C. J., & Beik, G. Y. (2020). Antioxidant activities of flower, berry and leaf of Panax ginseng C. A. Meyer. Korean Journal of Food Science and Technology, 52(4), 342–349. https://www.dbpia.co.kr/Journal/articleDetail?nodeId=NODE09871453
  192. Sadeghian, M., Rahmani, S., Zendehdel, M., Hosseini, S. A., & Zare Javid, A. (2020). Ginseng and cancer-related fatigue: a systematic review of clinical trials. Nutrition and Cancer, 73(8), 1270–1281. https://doi.org/10.1080/01635581.2020.1795691
  193. Sala, F., Mulet, J., Choi, S., Jung, S. Y., Nah, S. Y., Rhim, H., Valor, L. M., Criado, M., & Sala, S. (2002). Effects of ginsenoside Rg2 on human neuronal nicotinic acetylcholine receptors. Journal of Pharmacology and Experimental Therapeutics, 301(3), 1052–1059. https://doi.org/10.1124/jpet.301.3.1052
  194. Saleem, S., Muhammad, G., Hussain, M. A., Altaf, M., & Abbas Bukhari, S. N. (2020). Withania somnifera L.: insights into the phytochemical profile, therapeutic potential, clinical trials, and future prospective. Iranian Journal of Basic Medical Sciences, 23(12), 1501-1526. https://doi.org/10.22038/IJBMS.2020.44254.10378
  195. Salve, J., Kale, S., Prajapati, B. L., Sparavigna, A., Savant, M., Ademola, J., & Langade, D. (2025). Safety of 12-Months administration of Ashwagandha (Withania somnifera) standardized root extract in healthy adults: a prospective, observational study. Phytotherapy Research, 1–11. https://doi.org/10.1002/PTR.70096
  196. Salve, J., Pate, S., Debnath, K., & Langade, D. (2019). Adaptogenic and anxiolytic effects of ashwagandha root extract in healthy adults: a double-blind, randomized, placebo-controlled clinical study. Cureus, 11(12), e6466. https://doi.org/10.7759/cureus.6466
  197. Sánchez, I. A., Cuchimba, J. A., Pineda, M. C., Argüello, Y. P., Kočí, J., Kreider, R. B., Petro, J. L., & Bonilla, D. A. (2023). Adaptogens on depression-related outcomes: a systematic integrative review and rationale of synergism with physical activity. International Journal of Environmental Research and Public Health, 20(7), 5298. https://doi.org/10.3390/IJERPH20075298
  198. Sangiovanni, E., Brivio, P., Dell’Agli, M., & Calabrese, F. (2017). Botanicals as modulators of neuroplasticity: focus on BDNF. Neural Plasticity, 2017(1), 5965371. https://doi.org/10.1155/2017/5965371
  199. Searels, J. M., Keen, K. D., Horton, J. L., Clarke, H. D., & Ward, J. R. (2013). Comparing ginsenoside production in leaves and roots of wild American ginseng (Panax quinquefolius). American Journal of Plant Sciences, 4(6), 1252–1259. https://doi.org/10.4236/AJPS.2013.46154
  200. Seki, H., Tamura, K., & Muranaka, T. (2015). P450s and UGTs: key players in the structural diversity of triterpenoid saponins. Plant and Cell Physiology, 56(8), 1463–1471. https://doi.org/10.1093/PCP/PCV062
  201. Sengupta, P., Agarwal, A., Pogrebetskaya, M., Roychoudhury, S., Durairajanayagam, D., & Henkel, R. (2018). Role of Withania somnifera (Ashwagandha) in the management of male infertility. Reproductive BioMedicine Online, 36(3), 311–326. https://doi.org/10.1016/J.RBMO.2017.11.007
  202. Shao, J. W., Jiang, J. L., Zou, J. J., Yang, M. Y., Chen, F. M., Zhang, Y. J., & Jia, L. (2020). Therapeutic potential of ginsenosides on diabetes: from hypoglycemic mechanism to clinical trials. Journal of Functional Foods, 64, 103630. https://doi.org/10.1016/J.JFF.2019.103630
  203. Sharan, P., & Vellapandian, C. (2024). Hypothalamic-Pituitary-Adrenal (HPA) Axis: unveiling the potential mechanisms involved in stress-induced Alzheimer’s disease and depression. Cureus, 16(8), e67595. https://doi.org/10.7759/CUREUS.67595
  204. Shim, Y., Lee, Y. S., Kim, Y., Lee, S. E., Suh, C., Ha, E., Joo, Y., Lee, H., Lee, S., Shin, W. C., Yoon, S., Lyoo, I. K., & Lee, D. Y. (2025). Effects of white ginseng on reducing stress and tension by enhancing default mode network connectivity: a randomized, double-blinded placebo-controlled clinical trial. Journal of Ginseng Research, 49(6), 725-733. https://doi.org/10.1016/J.JGR.2025.08.004
  205. Shin, M. S., Lee, Y. J., Cho, I. H., & Yang, H. J. (2024). Brain plasticity and ginseng. Journal of Ginseng Research, 48(3), 286-297. https://doi.org/10.1016/J.JGR.2024.03.007
  206. Shin, M. S., Song, J. H., Choi, P., Lee, J. H., Kim, S. Y., Shin, K. S., Ham, J., & Kang, K. S. (2018). Stimulation of innate immune function by panax ginseng after heat processing. Journal of Agricultural and Food Chemistry, 66(18), 4652–4659. https://doi.org/10.1021/ACS.JAFC.8B00152
  207. Singh, A. A., Katiyar, S., & Song, M. (2025). Phytochemicals targeting BDNF signaling for treating neurological disorders. Brain Sciences, 15(3), 252. https://doi.org/10.3390/BRAINSCI15030252
  208. Singh, M., Bhutani, S., Dinkar, N., Mishra, A., Perveen, K., Alfagham, A. T., Khanam, M. N., Bhatt, S. C., & Suyal, D. C. (2023). Estimating the production of withaferin A and withanolide A in Withania somnifera (L.) dunal using aquaponics for sustainable development in hill agriculture. Frontiers in Plant Science, 14, 1215592. https://doi.org/10.3389/FPLS.2023.1215592
  209. Singh, M., Kuldeep, Chaudhary, P., Bhasin, S., Mehra, A., & Bhutani, S. (2024). Phytochemicals of Withania somnifera and their perspective on plant defense against stress. En R. Lone, S. Khan, & A. Mohamed Al-Sadi (eds.), Plant phenolics in biotic stress management (pp. 275–304). https://doi.org/10.1007/978-981-99-3334-1_11
  210. Singh, N., Bhalla, M., de Jager, P., & Gilca, M. (2011). An overview on ashwagandha: a rasayana (rejuvenator) of ayurveda. African Journal of Traditional, Complementary, and Alternative Medicines, 8(5), 208-213. https://doi.org/10.4314/AJTCAM.V8I5S.9
  211. Smith, S. J., Lopresti, A. L., & Fairchild, T. J. (2023). Exploring the efficacy and safety of a novel standardized ashwagandha (Withania somnifera) root extract (Witholytin®) in adults experiencing high stress and fatigue in a randomized, double-blind, placebo-controlled trial. Journal of Psychopharmacology, 37(11), 1091–1104. https://doi.org/10.1177/02698811231200023
  212. Song, Y., Chen, C., & Li, W. (2024). Ginsenoside Rb1 in cardiovascular and cerebrovascular diseases: a review of therapeutic potentials and molecular mechanisms. Chinese Herbal Medicines, 16(4), 489–504. https://doi.org/10.1016/J.CHMED.2024.09.006
  213. Speers, A. B., Cabey, K. A., Soumyanath, A., & Wright, K. M. (2021). Effects of Withania somnifera (Ashwagandha) on stress and the stress-related neuropsychiatric disorders anxiety, depression, and insomnia. Current Neuropharmacology, 19(9), 1468–1495. https://doi.org/10.2174/1570159X19666210712151556
  214. Speers, A. B., Lozano-Ortiz, A., & Soumyanath, A. (2024). Quantifying withanolides in plasma: pharmacokinetic studies and analytical methods. Nutrients, 16(22), 3836. https://doi.org/10.3390/NU16223836
  215. Sprengel, M., Laskowski, R., & Jost, Z. (2025). Withania somnifera (Ashwagandha) supplementation: a review of its mechanisms, health benefits, and role in sports performance. Nutrition & Metabolism, 22(9), 1–8. https://doi.org/10.1186/S12986-025-00902-7
  216. Stephen, A., Tune, B. X. J., Wu, Y. S., Batumalaie, K., Sekar, M., Sarker, Md. M. R., Subramaniyan, V., Fuloria, N. K., Fuloria, S., & Gopinath, S. C. B. (2025). Withanone as an emerging anticancer agent and understanding its molecular mechanisms: experimental and computational evidence. Current Cancer Drug Targets, 25(6), 574–585. https://doi.org/10.2174/0115680096290673240223043650
  217. Stojcheva, E. I., & Quintela, J. C. (2022). The effectiveness of Rhodiola rosea L. preparations in alleviating various aspects of life-stress symptoms and stress-induced conditions—encouraging clinical evidence. Molecules, 27(12), 3902. https://doi.org/10.3390/MOLECULES27123902
  218. Sun, M., Ye, Y., Xiao, L., Duan, X., Zhang, Y., & Zhang, H. (2017). Anticancer effects of ginsenoside Rg3 (Review). International Journal of Molecular Medicine, 39(3), 507–518. https://doi.org/10.3892/IJMM.2017.2857
  219. Sun, Y., Fu, X., Qu, Y., Chen, L., Liu, X., He, Z., Xu, J., Yang, J., Ma, W., Li, J., Guo, Q., & Zhang, Y. (2023). Characterization of ginsenosides from the root of panax ginseng by integrating untargeted metabolites using UPLC-Triple TOF-MS. Molecules, 28(5), 2068. https://doi.org/10.3390/MOLECULES28052068
  220. Sutopo, N. C., Qomaladewi, N. P., Lee, H. W., Lee, M. S., Kim, J. H., & Cho, J. Y. (2025). Comprehensive understanding and underlying molecular mechanisms of the adaptogenic effects of Panax ginseng. Journal of Ginseng Research, 49(4), 356-365. https://doi.org/10.1016/J.JGR.2025.03.013
  221. Syed, R. U., Hadi, M. A., Almarir, A. M., Alahmari, A. M., Alremthi, Y. H., Alsagri, A. A. A., Laimooniah, D., & Break, M. K. B. (2024). Rhodiola rosea L. extract ameliorates ethanol-induced gastric ulcer in rats by alleviating oxidative stress and inflammation via NF-κB pathway inhibition. Current Plant Biology, 40, 100421. https://doi.org/10.1016/j.cpb.2024.100421
  222. Tallon, M. J., Koturbash, I., & Blum, J. L. (2025). A systematic and ethnobotanical review of ashwagandha’s (Withania Somnifera) teratogenic and abortifacient potentials. Phytotherapy Research. https://doi.org/10.1002/PTR.70079
  223. Tandon, N., & Yadav, S. S. (2020). Safety and clinical effectiveness of Withania Somnifera (Linn.) Dunal root in human ailments. Journal of Ethnopharmacology, 255, 112768. https://doi.org/10.1016/j.jep.2020.112768
  224. Tang, K., Qin, W., Wei, R., Jiang, Y., Fan, L., Wang, Z., & Tan, N. (2022). Ginsenoside Rd ameliorates high glucose-induced retinal endothelial injury through AMPK-STRT1 interdependence. Pharmacological Research, 179, 106123. https://doi.org/10.1016/j.phrs.2022.106123
  225. Tang, M. M., Zhao, S. T., Li, R. Q., & Hou, W. (2023). Therapeutic mechanisms of ginseng in coronary heart disease. Frontiers in Pharmacology, 14, 1271029. https://doi.org/10.3389/FPHAR.2023.1271029
  226. Tang, P., Liu, S., Zhang, J., Ai, Z., Hu, Y., Cui, L., Zou, H., Li, X., Wang, Y., Nan, B., & Wang, Y. (2024). Ginsenosides as dietary supplements with immunomodulatory effects: a review. Applied Biological Chemistry, 67(1), 1–17. https://doi.org/10.1186/S13765-024-00881-Y
  227. Tharakan, A., Shukla, H., Benny, I. R., Tharakan, M., George, L., & Koshy, S. (2021). Immunomodulatory effect of withania somnifera (Ashwagandha) extract—A randomized, double-blind, placebo controlled trial with an open label extension on healthy participants. Journal of Clinical Medicine, 10(16), 3644. https://doi.org/10.3390/JCM10163644
  228. Tian, Z. F., Hu, R. Y., Wang, Z., Wang, Y. J., & Li, W. (2024). Molecular mechanisms behind the inhibitory effects of ginsenoside Rg3 on hepatic fibrosis: a review. Archives of Toxicology, 99(2), 541–561. https://doi.org/10.1007/S00204-024-03941-W
  229. Tinsley, G. M., Jagim, A. R., Potter, G. D. M., Garner, D., & Galpin, A. J. (2024). Rhodiola rosea as an adaptogen to enhance exercise performance: a review of the literature. British Journal of Nutrition, 131(3), 461–473. https://doi.org/10.1017/S0007114523001988
  230. Todorova, V., Ivanov, K., Delattre, C., Nalbantova, V., Karcheva-Bahchevanska, D., & Ivanova, S. (2021). Plant adaptogens-history and future perspectives. Nutrients, 13(8), 2861. https://doi.org/10.3390/NU13082861
  231. Tóth-Mészáros, A., Garmaa, G., Hegyi, P., Bánvölgyi, A., Fenyves, B., Fehérvári, P., Harnos, A., Gergő, D., Nguyen Do To, U., & Csupor, D. (2023). The effect of adaptogenic plants on stress: a systematic review and meta-analysis. Journal of Functional Foods, 108, 105695. https://doi.org/10.1016/J.JFF.2023.105695
  232. van Diermen, D., Marston, A., Bravo, J., Reist, M., Carrupt, P. A., & Hostettmann, K. (2009). Monoamine oxidase inhibition by Rhodiola rosea L. roots. Journal of Ethnopharmacology, 122(2), 397–401. https://doi.org/10.1016/J.JEP.2009.01.007
  233. Verma, N., Gupta, S. K., Tiwari, S., & Mishra, A. K. (2021). Safety of ashwagandha root extract: a randomized, placebo-controlled, study in healthy volunteers. Complementary Therapies in Medicine, 57, 102642. https://doi.org/10.1016/j.ctim.2020.102642
  234. Vittal, M., & Vinciguerra, M. (2025). Enhancing healthspan with Ashwagandha (Withania somnifera): a comprehensive review of its multifaceted geroprotective benefits. Biogerontology, 26(5), 1–20. https://doi.org/10.1007/S10522-025-10320-0
  235. Wang, C. H., Safwan, S., Cheng, M. C., Liao, T. Y., Cheng, L. C., Chen, T. A., Kuo, Y. H., Lin, Y. F., & Lee, C. K. (2020). Protective evaluation of compounds extracted from root of rhodiola rosea l. against methylglyoxal-induced toxicity in a neuronal cell line. Molecules, 25(12), 2801. https://doi.org/10.3390/MOLECULES25122801
  236. Wang, I. L., Su, Y., Zhang, L., Tang, M., & Chen, Y. M. (2025). Combined Rhodiola rosea and eccentric training boost endurance performance and lower-limb reactive strength in recreationally active women. Frontiers in Physiology, 16, 1663086. https://doi.org/10.3389/FPHYS.2025.1663086
  237. Wang, Q., Wei, L., Chen, G., & Chen, Q. (2025). Ginsenoside Rg1 in Parkinson’s disease: from basic research to clinical applications. Frontiers in Pharmacology, 16, 1490480. https://doi.org/10.3389/FPHAR.2025.1490480
  238. Wang, S., Feng, Y., Zheng, L., He, P., Tan, J., Cai, J., Wu, M., & Ye, X. (2023). Rosavin: research advances in extraction and synthesis, pharmacological activities and therapeutic effects on diseases of the characteristic active ingredients of Rhodiola rosea L. Molecules, 28(21), 7412. https://doi.org/10.3390/MOLECULES28217412
  239. Wang, W., Rayburn, E. R., Zhao, Y., Wang, H., & Zhang, R. (2009). Novel Ginsenosides 25-OH-PPD and 25-OCH3-PPD as experimental therapy for pancreatic cancer: anticancer activity and mechanisms of action. Cancer Letters, 278(2), 241-248. https://doi.org/10.1016/J.CANLET.2009.01.005
  240. Wang, X., Wang, R., Qiao, Y., & Li, Y. (2022). Progress on the efficacy and mechanism of action of panax ginseng monomer saponins treat toxicity. Frontiers in Pharmacology, 13, 1022266. https://doi.org/10.3389/FPHAR.2022.1022266
  241. Wang, X., Yang, X., Gao, Z., Zeng, J., & Liu, Y. (2025). The effect of Rhodiola rosea supplementation on endurance performance and related biomarkers: a systematic review and meta-analysis. Frontiers in Nutrition, 12, 1645346. https://doi.org/10.3389/FNUT.2025.1645346
  242. Wang, Y., Li, G., Chen, T., Wu, W., Yan, Z., & Li, X. (2023). Anticancer effect and molecular mechanism of ginsenoside Rg3 in various cancer types. Intelligent Pharmacy, 1(2), 52–63. https://doi.org/10.1016/J.IPHA.2023.04.012
  243. Wegener, T., Edwards, D., & Kasper, S. (2023). The potential role of Rhodiola rosea L. extract WS® 1375 for patients with post-COVID-19 fatigue. Healthbook TIMES Das Schweizer Ärztejournal Journal Des Médecins Suisses, 8(1), 56–61. https://doi.org/10.36000/HBT.2023.09.001
  244. Wiciński, M., Fajkiel-Madajczyk, A., Sławatycki, J., Szambelan, M., Szyperski, P., Wojciechowski, P., Wójcicki, J., & Gawryjołek, M. (2025). Ashwagandha (Withania somnifera) and its effects on well-being-a review. Nutrients, 17(13), 2143. https://doi.org/10.3390/NU17132143
  245. Wróbel-Biedrawa, D., & Podolak, I. (2024). Anti-Neuroinflammatory Effects of Adaptogens: A Mini-Review. Molecules, 29(4), 866. https://doi.org/10.3390/MOLECULES29040866
  246. Wu, J., Yang, Y., Wan, Y., Xia, J., Xu, J. F., Zhang, L., Liu, D., Chen, L., Tang, F., Ao, H., & Peng, C. (2022). New insights into the role and mechanisms of ginsenoside Rg1 in the management of Alzheimer’s disease. Biomedicine & Pharmacotherapy, 152, 113207. https://doi.org/10.1016/J.BIOPHA.2022.113207
  247. Wu, L., Bai, L., Dai, W., Wu, Y., Xi, P., Zhang, J., & Zheng, L. (2024). Ginsenoside Rg3: a review of its anticancer mechanisms and potential therapeutic applications. Current Topics in Medicinal Chemistry, 24(10), 869–884. https://doi.org/10.2174/0115680266283661240226052054
  248. Xia, G. Y., Cao, S. J., Chen, L. X., & Qiu, F. (2022). Natural withanolides, an update. Natural Product Reports, 39(4), 784–813. https://doi.org/10.1039/D1NP00055A
  249. Xia, N., Li, J., Wang, H., Wang, J., & Wang, Y. (2016). Schisandra chinensis and Rhodiola rosea exert an anti-stress effect on the HPA axis and reduce hypothalamic c-Fos expression in rats subjected to repeated stress. Experimental and Therapeutic Medicine, 11(1), 353–359. https://doi.org/10.3892/ETM.2015.2882
  250. Xiao, H., Zhang, Y., Zhang, B., Wu, J., & Li, X. (2025). Ginsenoside Rg3 exerts anticancer effects in lung cancer through metabolite Histon H3. American Journal of Translational Research, 17(5), 3994. https://doi.org/10.62347/YJZW4664
  251. Xiaodan, S., & Ying, C. (2022). Role of ginsenoside Rh2 in tumor therapy and tumor microenvironment immunomodulation. Biomedicine & Pharmacotherapy, 156, 113912. https://doi.org/10.1016/J.BIOPHA.2022.113912
  252. Xiu, Y., Li, X., Sun, X., Xiao, D., Miao, R., Zhao, H., & Liu, S. (2019). Simultaneous determination and difference evaluation of 14 ginsenosides in Panax ginseng roots cultivated in different areas and ages by high-performance liquid chromatography coupled with triple quadrupole mass spectrometer in the multiple reaction–monitoring mode combined with multivariate statistical analysis. Journal of Ginseng Research, 43(4), 508-516. https://doi.org/10.1016/J.JGR.2017.12.001
  253. Xu, W., Yang, T., Zhang, J., Li, H., & Guo, M. (2024). Rhodiola rosea: a review in the context of PPPM approach. The EPMA Journal, 15(2), 233-259. https://doi.org/10.1007/S13167-024-00367-3
  254. Xu, X., Qu, W., Jia, Z., Han, T., Liu, M., Bai, Y., Wang, M., Lin, R., Hua, Q., & Li, X. (2021). Effect of cultivation ages on anti-inflammatory activity of a new type of red ginseng. Biomedicine & Pharmacotherapy, 136, 111280. https://doi.org/10.1016/J.BIOPHA.2021.111280
  255. Xue, Y., Zhang, R., Li, T., Deng, Q., Luo, W., Chang, R., Zeng, D., Tan, J., Sun, T., Liu, Y. G., Xiang, Y., Zhu, Q., & Chai, N. (2025). Sustainable production of ginsenosides: advances in biosynthesis and metabolic engineering. Plants, 14(18), 2821. https://doi.org/10.3390/PLANTS14182821
  256. Yang, L., Chen, X., & Gao, Y. (2022). Efficacy of different concentrations of withanolides in ashwagandha supplements for insomnia and enhancing energy level. Current Developments in Nutrition, 6(1), 881. https://doi.org/10.1093/CDN/NZAC067.001
  257. Yang, Q., Xiong, C., Zhang, J., Ming, Y., Zhang, S., Wang, L., Wang, H., Xu, R., & Wang, B. (2024). Chemical and transcriptomic analyses provide new insights into key genes for ginsenoside biosynthesis in the Rhizome of Panax japonicus C. A. Meyer. Molecules, 29(20), 4936. https://doi.org/10.3390/MOLECULES29204936/S1
  258. Yang, Y., Nan, Y., Du, Y., Liu, W., Ning, N., Chen, G., Gu, Q., & Yuan, L. (2024). Ginsenosides in cancer: proliferation, metastasis, and drug resistance. Biomedicine & Pharmacotherapy, 177, 117049. https://doi.org/10.1016/J.BIOPHA.2024.117049
  259. Yao, F., Li, X., Sun, J., Cao, X., Liu, M., Li, Y., & Liu, Y. (2021). Thermal transformation of polar into less-polar ginsenosides through demalonylation and deglycosylation in extracts from ginseng pulp. Scientific Reports, 11(1), 1513. https://doi.org/10.1038/S41598-021-81079-W
  260. Yao, W., & Guan, Y. (2022). Ginsenosides in cancer: a focus on the regulation of cell metabolism. Biomedicine & Pharmacotherapy, 156, 113756. https://doi.org/10.1016/J.BIOPHA.2022.113756
  261. Yaribeygi, H., Panahi, Y., Sahraei, H., Johnston, T. P., & Sahebkar, A. (2017). The impact of stress on body function: a review. EXCLI Journal, 16, 1057–1072. https://doi.org/10.17179/EXCLI2017-480
  262. Ye, X. W., Li, C. S., Zhang, H. X., Li, Q., Cheng, S. Q., Wen, J., Wang, X., Ren, H. M., Xia, L. J., Wang, X. X., Xu, X. F., & Li, X. R. (2023). Saponins of ginseng products: a review of their transformation in processing. Frontiers in Pharmacology, 14, 1177819. https://doi.org/10.3389/FPHAR.2023.1177819
  263. Ye, Z., Wang, S., Wan, Z., Huang, B., & Guo, J. (2025). Targeting NADPH oxidase-driven oxidative stress in diabetic cardiomyopathy: mechanisms and therapeutic perspectives. Frontiers in Pharmacology, 16, 1610429. https://doi.org/10.3389/FPHAR.2025.1610429
  264. Yi, Y. S. (2024). Pharmacological potential of ginseng and ginsenosides in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Journal of Ginseng Research, 48(2), 122–128. https://doi.org/10.1016/J.JGR.2023.11.003
  265. You, L., Cha, S., Kim, M. Y., & Cho, J. Y. (2022). Ginsenosides are active ingredients in Panax ginseng with immunomodulatory properties from cellular to organismal levels. Journal of Ginseng Research, 46(6),
  266. 711–721. https://doi.org/10.1016/J.JGR.2021.12.007
  267. Yuan, W., Wang, Q., Pei, W., Li, S., Wang, T., Song, H., Teng, D., Kang, T., & Zhang, H. (2024). Age-induced changes in ginsenoside accumulation and primary metabolic characteristics of Panax Ginseng in transplantation mode. Journal of Ginseng Research, 48(1), 103–111. https://doi.org/10.1016/J.JGR.2023.09.003
  268. Yun, Y. B., Kwon, H. Y., & Um, Y. (2024). Changes in growth characteristics and ginsenoside contents of wild-simulated ginseng with different harvest times in South Korea. Applied Biological Chemistry, 67(66), 1–10. https://doi.org/10.1186/S13765-024-00920-8
  269. Yusuf, N., Nasti, T. H., Ahmad, I., Chowdhury, S., Mohiuddin, H., Xu, H., Athar, M., Timares, L., & Elmets, C. A. (2015). In vivo suppression of heat shock protein (HSP)27 and HSP70 accelerates DMBA-induced skin carcinogenesis by inducing antigenic unresponsiveness to the initiating carcinogenic chemical. The Journal of Immunology, 194(10), 4796–4803. https://doi.org/10.4049/JIMMUNOL.1402804
  270. Zakharenko, A. M., Razgonova, M. P., Pikula, K. S., & Golokhvast, K. S. (2021). Simultaneous determination of 78 compounds of Rhodiola rosea extract by supercritical CO2-extraction and HPLC-ESI-MS/MS spectrometry. Biochemistry Research International, 2021(1), 9957490. https://doi.org/10.1155/2021/9957490
  271. Zhai, Z., & Gao, Y. (2025). Protective effects of ginsenosides in cerebral small vessel disease: cellular and molecular mechanisms. Journal of Ginseng Research, 49(6), 640-651. https://doi.org/10.1016/J.JGR.2025.08.007
  272. Zhang, L., Yin, H., Xie, Y., Zhang, Y., Dong, F., Wu, K., Yang, L., & Lv, H. (2024). Exploring the anti oxidative mechanisms of Rhodiola rosea in ameliorating myocardial fibrosis through network pharmacology and in vitro experiments. Molecular Medicine Reports, 30(6), 1-13. https://doi.org/10.3892/MMR.2024.13338
  273. Zhang, Z., Yang, Y., Xu, Y., Liu, Y., Li, H., & Chen, L. (2023). Molecular targets and mechanisms of anti-cancer effects of withanolides. Chemico-Biological Interactions, 384, 110698. https://doi.org/10.1016/J.CBI.2023.110698
  274. Zhao, L., Zhang, T., & Zhang, K. (2024). Pharmacological effects of ginseng and ginsenosides on intestinal inflammation and the immune system. Frontiers in Immunology, 15, 1353614. https://doi.org/10.3389/FIMMU.2024.1353614
  275. Zheng, S., Zheng, H., Zhang, R., Piao, X., Hu, J., Zhu, Y., & Wang, Y. (2022). Immunomodulatory effect of Ginsenoside Rb2 against Cyclophosphamide-induced immunosuppression in mice. Frontiers in Pharmacology, 13, 927087. https://doi.org/10.3389/FPHAR.2022.927087
  276. Zhong, Y., Chen, Y., Pan, Z., Tang, K., Zhong, G., Guo, J., Cui, T., Li, T., Duan, S., Yang, X., Gao, Y., Wang, Q., & Zhang, D. (2022). Ginsenoside Rc, as an FXR activator, alleviates acetaminophen-induced hepatotoxicity via relieving inflammation and oxidative stress. Frontiers in Pharmacology, 13, 1027731. https://doi.org/10.3389/FPHAR.2022.1027731
  277. Zhou, B., Wu, L., Liu, D., Xie, X., Zhang, X., Liu, Y., Hao, B., Shi, G., Yu, S., Zheng, Z., Lin, L., Wang, M., & Qian, X. (2025). Ginsenoside Rb1 attenuates age-associated cognitive impairment by modulating oxidative stress and the SIRT1/eNOS/NO axis. Journal of Ginseng Research, 49(6), 683-691. https://doi.org/10.1016/J.JGR.2025.06.002
  278. Zhou, G., Wang, C. Z., Mohammadi, S., Sawadogo, W. R., Ma, Q., & Yuan, C. S. (2023). Pharmacological effects of ginseng: multiple constituents and multiple actions on humans. The American Journal of Chinese Medicine, 51(5), 1085–1104. https://doi.org/10.1142/S0192415X23500507
  279. Zhou, P., Xie, W., He, S., Sun, Y., Meng, X., Sun, G., & Sun, X. (2019). Ginsenoside Rb1 as an anti-diabetic agent and its underlying mechanism analysis. Cells, 8(3), 204. https://doi.org/10.3390/CELLS8030204
  280. Zhu, G., Wang, Y., Li, J., & Wang, J. (2015). Chronic treatment with ginsenoside Rg1 promotes memory and hippocampal long-term potentiation in middle-aged mice. Neuroscience, 292, 81–89. https://doi.org/10.1016/j.neuroscience.2015.02.031
  281. Zhu, Z., Li, R., Qin, W., Zhang, H., Cheng, Y., Chen, F., Chen, C., Chen, L., & Zhao, Y. (2021). Target engagement of ginsenosides in mild cognitive impairment using mass spectrometry-based drug affinity responsive target stability. Journal of Ginseng Research, 46(6), 750-758. https://doi.org/10.1016/J.JGR.2021.12.003
  282. Zhuang, S., Shi, F., Cannella, N., Ubaldi, M., Ciccocioppo, R., Li, H., & Qin, D. (2025). Pharmacological mechanism and drug research prospects of ginsenoside Rb1 as an antidepressant. Antioxidants 2025, 14(2), 238. https://doi.org/10.3390/ANTIOX14020238
  283. Zhuang, W., Yue, L., Dang, X., Chen, F., Gong, Y., Lin, X., & Luo, Y. (2019). Rosenroot (Rhodiola): potential applications in aging-related diseases. Aging and Disease, 10(1), 134-146. https://doi.org/10.14336/AD.2018.0511