Rhodiola rosea Linnaeus improves learning, memory, and symptoms of depression – an integrative review
DOI:
https://doi.org/10.21527/2176-7114.2026.51.15651Keywords:
antidepressive agents, neurogenesis, “golden root”Abstract
Traditional antidepressants are associated with side effects that lead to treatment discontinuation. Natural alternatives have been studied, such as Rhodiola rosea (RR), for treating depression. This integrative review investigated the effects of RR in animals with induced depression to assess its effectiveness in alleviating depressive symptoms and improving learning and memory. The PubMed, Scopus, Web of Science, and ScienceDirect databases were searched for relevant studies using the terms “Salidroside,” “Rhodioloside,” “Rhodiola rosea,” “depression,” “depressive disorder,” “depression, chemical,” and “animal.” The RR extract and salidroside were evaluated in six and eight studies, respectively. RR extract and salidroside improve cognitive function, neuroplasticity, and serotonin and corticosterone levels in rats. Using Rhodiola rosea extract or salidroside improves learning and memory and reduces neuronal damage caused by depression.
References
1. Carvalho R. Porque o Brasil tem a população mais depressiva da América Latina? 2023. [access at 2025 Aug 2]. Available at https://ipqhc.org.br/2023/11/05/por-que-o-brasil-tem-a-populacao-mais-depressiva-da-america-latina/#:~:text=Assim%20witho%20Maria%2C%20300%20milh%C3%B5es,de%20atendimento%20para%20a%20depress%C3%A3o
2. MS – Ministério da Saúde. Na América Latina, Brasil é o país with maior prevalência de depressão. 2022. [access at 2023 Nov 17].
3. UMANE – Observatório APS – Número de internações por depressão. 2022. [access at 2023 Nov 17]. Available at: https://observatoriodaaps.with.br/tema/depressao
4. McDonald T. How depression affects your thinking skills. Neuroscience News. 2018. [access at 2023 Aug 13]. Available at: https://neurosciencenews.with/depression-thinking-skills-9297/
5. Tai HH, Cha J, Vedaei F, Dunlop BW, Craighead WD, Mayberg HS, Choi KS. Treatment-specific hippocampal subfield volume changes with antidepressant medication or cognitive-behavior therapy in treatment-naïve depression. Front Psychiatry 2021; 12: 718539. https://doi.org/10.3389/fpsyt.2021.718539
6. Santos MAO, Bezerra LS, Carvalho ARMR, Brainer-Lima AM. Global hippocampal atrophy in major depressive disorder: a meta-analysis of magnetic resonance imaging studies. Trends Psychiatry Psychother 2018; 40(4): 369-378. https://doi.org/10.1590/2237-6089-2017-0130
7. Borba EM, Duarte JA, Bristot G, Scotton E, Camozzato AL, Chaves MLF. Brain-derived neurotrophic factor serum levels and hippocampal volume in mild cognitive impairment and dementia due to Alzheimer disease. Dement Geriatr Cogn Disord Extra 2016; 6(3): 559-567. https://doi.org/10.1159/000450601
8. Taylor WD, McQuoid DR, Payne ME, Zannas AS, MacFall JR, Steffens DC. Hippocampus atrophy and the longitudinal course of late-life depression. Am J Geriatr Psychiatry 2014; 22(12): 1504-1512. https://doi.org/10.1016/j.jagp.2013.11.004
9. Troubat R, Barone P, Leman S, Desmidt T, Cressant A, Atanasova B, Brizard B, El Hage W, Surget A, Belzung C, Camus V. Neuroinflammation and depression: a review. Eur J Neurosci 2020; 53(1): 151-171. https://doi.org/10.1111/ejn.14720
10. Felger JC, Haroon E, Patel TA, Goldsmith DR, Wommack EC, Woolwine BJ, Le NA, Feinberg R, Tansey MG, Miller, AH. What does plasma CRP tell us about peripheral and central inflammation in depression? Mol Psychiatry 2018; 25(6): 1301-1311. https://doi.org/10.1038/s41380-018-0096-3
11. Berk M, Williams LJ, Jacka FN, O’Neil A, Pasco JA, Moylan S, Allen NB, Stuart AL, Hayley AC, Byrne ML, Maes M. So depression is an inflammatory disease, but where does the inflammation withe from? BMC Med 2013; 11: 200. https://doi.org/10.1186/1741-7015-11-200
12. Shao X, Zhu G. Associations among monoamine neurotransmitter pathways, personality traits, and major depressive disorder. Front Psychiatry 2020; 11: 381. https://doi.org/10.3389/fpsyt.2020.00381
13. Kanen JW, Arntz FE, Yellowlees R, Cardinal RN, Price A, Christmas DM, Apergis-Schoute AM, Sahakian BJ, Robbins TW. Serotonin depletion amplifies distinct human social emotions as a function of individual differences in personality. Transl Psychiatry 2021; 11(1): 81. https://doi.org/10.1038/s41398-020-00880-9
14. Obermanns J, Flasbeck V, Steinmann S, Juckel G, Emons B. Investigation of the serotoninergic activity and the serotonin content in serum and platelet, and the possible role of the serotonin transporter in patients with depression. Behav Sci 2022; 12(6): 178. https://doi.org/10.3390/bs12060178
15. Liu Y, Zhao J, Guo W. Emotional roles of mono-aminergic neurotransmitters in major depressive disorder and anxiety disorders. Front Psychol 2018; 9: 2201. https://doi.org/10.3389/fpsyg.2018.02201
16. Belujon P, Grace AA. Dopamine system dysregulation in major depressive disorders. Int J Neuropsychopharmacol 2017; 20(12): 1036-1046. https://doi.org/10.1093/ijnp/pyx056
17. Dubol M, Trichard C, Leroy C, Granger B, Tzavara E, Martinot JL, Artiges E. Lower midbrain dopamine transporter availability in depressed patients: report from high-resolution PET imaging. J Affect Disord 2020; 262: 273-277. https://doi.org/10.1016/j.jad.2019.10.041
18. Tafet GE, Nemeroff CB. The links between stress and depression: psychoneuroendocrinological, genetic, and environmental interactions. Neuropsychiatry Clin Neursci 2016; 28(2): 77-88. https://doi.org/10.1176/appi.neuropsych.15030053
19. Stojcheva EI, Quintela JC. The effectiveness of Rhodiola rosea L. preparations in alleviating various aspects of life-stress symptoms and stress-induced conditions – encouraging clinical evidence. Molecules 2022; 27(12): 3902. https://doi.org/10.3390/molecules27123902
20. Tesser CD, Sousa IMC, Nascimento MC. Práticas integrativas e withplementares na atenção primária à saúde brasileira. Saúde Debate 2018; 42(1): 174-188. https://doi.org/10.1590/0103-11042018S112
21. Vasileva LV, Getova DP, Doncheva ND, Marchev AS, Georgiev MI. Beneficial effect of withmercial Rhodiola extract in rats with scopolamine-induced memory impairment on active avoidance. J Ethnopharmacol 2016; 193: 586-591. https://doi.org/10.1016/j.jep.2016.10.011
22. Vasileva LV, Saracheva KE, Ivanovska MV, Petrova AP, Sucouglu E, Murdjeva MA, Getova-Spasova D. Beneficial effect of chronic treatment with extracts from Rhodiola rosea L. and Curcuma longa L. on the immunoreactivity of animals subjected to a chronic mild stress model. Folia Med 2017; 59(4): 443-453. https://doi.org/10.1515/folmed-2017-0046
23. Liu H, Lv P, Wu H, Zhang K, Xu F, Zheng L, Zhao J. The proliferation enhancing effects of salidroside of Schwann cells in vitro. Evid Based Withplement Alternat Med 2017; 2017: 4673289. https://doi.org/10.1155/2017/4673289
24. Jin H, Pei L, Shu X, Yang X, Yan T, Wu Y, Wei N, Yan H, Wang S, Yao C, Liu D, Tian Q, Wang L, Lu Y. Therapeutic intervention of learning and memory decays by salidroside stimulation of neurogenesis in aging. Mol Neurobiol 2016; 53(2): 851-866. https://doi.org/10.1007/s12035-014-9045-6
25. Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan – a web and mobile app for systematic reviews. Syst. Rev 2016; 5: 210. https://doi.org/10.1186/s13643-016-0384-4
26. Perfumi M, Mattioli L. Adaptogenic and central nervous system effects of single doses of 3% rosavin and 1% salidroside Rhodiola rosea L. extract in mice. Phytother Res 2007; 21(1): 37-43. https://doi.org/10.1002/ptr.2013
27. Panossian A, Nikoyan N, Ohanyan N, Hovhannisyan A, Abrahamyan H, Gabrielyan E, Wikman G. Withparative study of Rhodiola preparations on behavioral despair of rats. Phytomedicine 2008; 15(1-2): 84-91. https://doi.org/10.1016/j.phymed.2007.10.003
28. Chen QG, Zeng YS, Qu ZQ, Tang JY, Qin YJ, Chung P, Wong R, Hägg U. The effects of Rhodiola rosea extract on 5-HT level, cell proliferation and quantity of neurons at cerebral hippocampus of depressive rats. Phytomedicine 2009; 16(9): 830-838. https://doi.org/10.1016/j.phymed.2009.03.011
29. Mattioli L, Funari C, Perfumi M. Effects of Rhodiola rosea L. extract on behavioural and physiological alterations induced by chronic mild stress in female rats. J Psychopharmacol 2009; 23(2): 130-142. https://doi.org/10.1177/0269881108089872
30. Yang SJ, Yu HY, Kang DY, Ma ZQ, Qu R, Fu Q, Ma SP. Antidepressant-like effects of salidroside on olfactory bulbectomy-induced pro-inflammatory cytokine production and hyperactivity of HPA axis in rats. Pharmacol Biochem Behav 2014; 124: 451-457. https://doi.org/10.1016/j.pbb.2014.07.015
31. Zhu L, Wei T, Gao J, Chang X, He H, Miao M, Yan T. Salidroside attenuates lipopolysaccharide (LPS) induced serum cytokines and depressive-like behavior in mice. Neurosci Lett 2015; 606: 1-6. https://doi.org/10.1016/j.neulet.2015.08.025
32. Palmeri A, Mammana L, Tropea MR, Gulisano W, Puzzo D. Salidroside, a bioactive withpound of Rhodiola rosea, ameliorates memory and emotional behavior in adult mice. J Alzheimers Dis 2016; 52(1): 65-75. https://doi.org/10.3233/jad-151159
33. Zhang X, Du Q, Liu C, Yang Y, Wang J, Duan S, Duan J. Rhodioloside ameliorates depressive behavior via up-regulation of monoaminergic system activity and anti-inflammatory effect in olfactory bulbectomized rats. Int Immunopharmacol 2016; 36: 300-304. https://doi.org/10.1016/j.intimp.2016.05.008
34. Vasileva LV, Saracheva KE, Ivanovska MV, Petrova AP, Marchev AS, Georgiev MI, Murdjeva MA, Getova DP. Antidepressant-like effect of salidroside and curcumin on the immunoreactivity of rats subjected to a chronic mild stress model. Food Chem Toxicol 2018; 121: 604-611. https://doi.org/10.1016/j.fct.2018.09.065
35. Fan Y, Bi Y, Chen H. Salidroside improves chronic stress induced depressive symptoms through microglial activation suppression. Front Pharmacol 2021; 12: 635762. https://doi.org/10.3389/fphar.2021.635762
36. Chai Y, Cai W, Fu Y, Wang Y, Zhang Y, Zhang X, Zhu L, Miao M, Yan T. Salidroside ameliorates depression by suppressing NLRP3-mediated pyroptosis via P2X7/NF-κB/NLRP3 signaling pathway. Front Pharmacol 2022; 13: 812362. https://doi.org/10.3389/fphar.2022.812362
37. Valvassori SS, Varela RB, Quevedo J. Animal models of mood disorders: focus on bipolar disorder and depression. In: Coon PM (Ed.) Animal models for the study of human disease. 2. ed. Londres: Elsevier, 2017. p. 991-1001. https://doi.org/10.1016/B978-0-12-809468-6.00038-3
38. Ozcan H, Aydin N, Aydin MD, Oral E, Gündogdu C, Sipal S, Halici Z. Olfactory bulbectomy and raphe nucleus relationship: a new vision for well-known depression model. Nord J Psychiatry 2020; 74(3): 194-200. https://doi.org/10.1080/08039488.2019.1689294
39. De Fruyt J, Sabble B, Demyttenaere K. Anhedonia in depressive disorder: a narrative review. Psychopathology 2020; 53(5-6): 274-281. https://doi.org/10.1159/000508773
40. Hoffman K. What can animal models tell us about depressive disorders? In: Hoffman K. Modeling Neuropsychiatric Disorders in Laboratory Animals. London: Elsevier, 2015. p. 35-86. https://doi.org/10.1016/B978-0-08-100099-1.00002-9
41. Yankelevitch-Yahave R, Franko M, Huly A, Doron R. The forced swim test as a model of depressive-like behavior. J Vis Exp 2015; 97: 52587. https://doi.org/10.3791/52587
42. Tang H, Wang J, Zhao L, Zhao XM. Rhodiola rosea L extract shows protective activity against Alzheimer’s disease in 3xTg-AD mice. Trop J Pharm Res 2017; 16(3): 509-514. https://doi.org/10.4314/tjpr.v16i3.3
43. Yau SY, Li A, So KF. Involvement of adult hippocampal neurogenesis in learning and forgetting. Neural Plast 2015; 2015: 717958. https://doi.org/10.1155/2015/717958
44. Limanaqi F, Biagioni F, Busceti CL, Polzella M, Fabrizi C, Fornai F. Potential antidepressant effects of Scutellaria baixalensis, Hericium erinaceus and Rhodiola rosea. Antioxidants 2020; 9(3): 234. https://doi.org/10.3390/antiox9030234
45. Haam J, Yakel JL. Cholinergic modulation of the hippocampal region and memory function. J Neurochem 2017; 142 (Suppl. 2): 111-121. https://doi.org/10.1111/jnc.14052
46. Maurer SV, Williams CL. The cholinergic system modulates memory and hippocampal plasticity via its interactions with non-neuronal cells. Front Immunol 2017; 8: 1489. https://doi.org/10.3389/fimmu.2017.01489
47. Polumackanycz M, Konieczynski P, Orhan IE, Abaci N, Viapiana A. Chemical withposition, antioxidant and anti-enzymatic activity of golden root (Rhodiola rosea L.) withmercial samples. Antioxidants 2022; 11(5): 919. https://doi.org/10.3390/antiox11050919
48. Wang CH, Safwan S, Cheng MC, Liao TY, Cheng LC, Chen TA, Kuo YH, Lin YF, Lee CK. Protective evaluation of withpounds extracted from root of Rhodiola rosea L. against methylglyoxal-induced toxicity in a neuronal cell line. Molecules 2020; 25(12): 2801. https://doi.org/10.3390/molecules25122801
49. Kim KJ, Jung YS, You DM, Lee SH, Lee G, Kwon KB, Kim DO. Neuroprotective effects of ethanolic extract from dry Rhodiola rosea L. rhizomes. Food Sci Biotechnol 2021; 30(2): 287-297. https://doi.org/10.1007/s10068-020-00868-7
50. Chen BY, Wang X, Wang ZY, Wang YZ, Chen LW, Luo ZJ. Brain-derived neurotrophic factor stimulates proliferation and differentiation of neural stem cells, possibly by triggering the Wnt/β-catenin signaling pathway. J Neurosci Res 2013; 91(1): 30-41. https://doi.org/10.1002/jnr.23138
51. Miyasaka Y, Yamamoto N. Neuronal activity patterns regulate brain-derived neurotrophic factor expression in cortical cells via neuronal circuits. Front Neurosci 2021; 15: 699583. https://doi.org/10.3389/fnins.2021.699583
52. Ramos JM, Galdeano DS. Educação física e o fator neurotrófico derivado do cérebro (BDNF) na aprendizagem escolar. Conexões 2019; 17: e019005. https://doi.org/10.20396/conex.v17i0.8651312
53. Duman RS, Deyama S, Fogaça, MV. Role of BDNF in the pathophysiology and treatment of depression: activity-dependent effects distinguish rapid-acting antidepressants. Eur. J. Neurosci. 2021; 53(1): 126-139. https://doi.org/10.1111/ejn.14630
54. Calabrese F, van der Doelen RHA, Guidotti G, Racagni G, Kozicz T, Homberg JR, Riva MA. Exposure to early life stress regulates Bdnf expression in SERT mutant rats in an anatomically selective fashion. J Neurochem 2015; 132(1): 146-154. https://doi.org/10.1111/jnc.12846
55. Numakawa T, Yokomaku D, Richards M, Hori H, Adachi N, Kunugi H. Functional interactions between steroid hormones and neurotrophin BDNF. World J Biol Chem 2010; 1(5): 133-143. https://doi.org/10.4331/wjbc.v1.i5.133
56. Zhao HB, Ma H, Ha XQ, Zheng P, Li XY, Zhang M, Dong JZ, Yang YS. Salidroside induces rat mesenchymal stem cells to differentiate into dopaminergic neurons. Cell Biol Int 2014; 38(4): 462-471. https://doi.org/10.1002/cbin.10217
57. Agapouda A, Grimm A, Lejri I, Eckert A. Rhodiola rosea extract counteracts stress in an adaptogenic response curve manner via elimination of ROS and induction of neurite outgrowth. Oxid Med Cell Longev 2022; 2022: 5647599. https://doi.org/10.1155/2022/5647599
58. Kubera M, Grygier B, Wrona D, Rogóz Z, Roman A, Basta-Kaim A, Budziszewska B, Leskiewicz M, Jantas D, Nowak W., Maes M, Lason W. Stimulatory effect of antidepressant drug pretreatment on progression of B16F10 melanoma in high-active male and female C57BL/6J mice. J Neuroimmunol 2011; 240-241: 34-44. https://doi.org/10.1016/j.jneuroim.2011.09.006
59. Concerto C, Infortuna C, Muscatello MRA, Bruno A, Zoccali R, Chusid E, Aguglia E, Battaglia F. Exploring the effect of adaptogenic Rhodiola rosea extract on neuroplasticity in humans. Withplement Ther Med 2018; 41: 141-146. https://doi.org/10.1016/j.ctim.2018.09.013
60. Mannucci C, Navarra M, Calzavara E, Caputti AP, Calapai G. Serotonin involvement in Rhodiola rosea attenuation of nicotine withdrawal signs in rats. Phytomedicine 2012; 19(12): 1117-1124. https://doi.org/10.1016/j.phymed.2012.07.001
61. van Diermen D, Marston A, Bravo J, Reist M, Carrupt PA, Hostettmann K. Monoamine oxidase inhibition by Rhodiola rosea L. roots. J Ethnopharmacol 2009; 122(2): 397-401. https://doi.org/10.1016/j.jep.2009.01.007
62. Sha Q, Madaj Z, Keaton S, Galvis MLE, Smart LA, Krzyzanowski S, Fazleabas AT, Leach R, Postolache TT, Achtyes ED, Brundin L. Cytokines and tryptophan metabolites can predict depressive symptoms in pregnancy. Transl Psychiatry 2022; 12: 35. https://doi.org/10.1038/s41398-022-01801-8
63. Bleibel L, Sokolowska P, Henrykowska G, Owczarek J, Wiktorowska-Owczarek A. Unveiling the anti-inflammatory effects of antidepressants: a systematic review of human studies over the last decade. Pharmaceuticals 2025; 18(6): 867. https://doi.org/10.3390/ph18060867
64. Vasileva LV, Ivanovska MV, Murdjeva MA, Saracheva, KE, Georgiev MI. Immunoregulatory natural withpounds in stress-induced depression: an alternative or an adjunct to conventional antidepressant therapy? Food Chem Toxicol 2019; 127: 81-88. https://doi.org/10.1016/j.fct.2019.03.004
65. Pooja, Bawa AS, Khanum F. Anti-inflammatory activity of Rhodiola rosea – “a second-generation adaptogen”. Phytother Res 2009; 23(8): 1099-1102. https://doi.org/10.1002/ptr.2749
66. Song D, Zhao M, Feng L, Wang P, Li Y, Li W. Salidroside attenuates acute lung injury via inhibition of inflammatory cytokine production. Biomed Pharmacother 2021; 142: 111949. https://doi.org/10.1016/j.biopha.2021.111949
67. Wohleb ES, Powell ND, Godbout JP, Sheridan JF. Stress-induced recruitment of bone marrow-derived monocytes to the brain promotes anxiety-like behavior. J. Neurosci 2013; 33(34): 13820-13833. https://doi.org/10.1523/jneurosci.1671-13.2013
68. Jesus MBN, Assunção JR. Implicações metabólicas do exercício físico no eixo hipotálamo-pituitária-adrenal. Prát. Cuidado: Rev Saúde Col 2020 [access at 2022 Jul 22]; 1: e9995. Avaliable at: https://revistas.uneb.br/index.php/saudecoletiva/article/view/9995
69. Dinel AL, Guinobert I, Lucas C, Blondeau C, Bardot V, Ripoche I, Berthomier L, Pallet V, Layé S, Joffre C. 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 Sci Nutr 2019; 7(11): 3827-3841. https://doi.org/10.1002/fsn3.1249
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