Mental health issues, including cognitive impairment, anxiety, and depression, have become a major global health challenge. Notably, conventional pharmacological treatments are often accompanied by adverse reactions. The traditional Chinese medicine concept of “Medicine and Food Homology (MFH)” provides an important direction for disease prevention and treatment.Panax ginseng C. A. Mey. (P. ginseng, Ren Shen) is a representative MFH substance that has increasingly recognized for its roles in improving cognitive function and regulating mood. However, there remains no systematic integration based on modern scientific evidence. This review aimed to systematically summarize existing research in order to clarify the therapeutic potential and mechanisms of P. ginseng and its products (Red Ginseng, Black Ginseng, ginsenosides, polysaccharides, etc.). For cognitive improvement, they act through multiple pathways, including inhibiting neuroinflammation, enhancing antioxidant capacity, improving mitochondrial metabolism, and regulating synaptic plasticity. For emotional regulation, they alleviate anxiety and depression by modulating the hypothalamic-pituitary-adrenal/hypothalamic-pituitary-gonadal axis, balancing neurotransmitters, and activating the brain-derived neurotrophic factor-tropomyosin receptor kinase B pathway. P. ginseng and its active components exhibit multi-target, network-based action characteristics and good safety profiles. However, there remain challenges, including unclear mechanisms for individual components and insufficient high-quality clinical evidence. Future studies are warranted to perform in-depth analysis of the synergistic mechanisms of active ingredients. Moreover, large-scale clinical trials are warranted to provide scientific support for the standardized application of P. ginseng in mental health.
Funding
This research was supported by the Department of Science and Technology of Jilin Province (20240305077YY).
CRediT authorship contribution statement
Zhe Wang: Investigation, resources, visualization, and writing – original draft, and writing – review & editing. Yueliang Sun: Investigation, resources, and writing – review & editing. Le Li: Visualization. Chenxuan Dong: Data curation, Investigation, Writing–review & editing. Tianying Chang: Validation and writing – review & editing. Yingzi Cui: Supervision and writing – review & editing. Jiajuan Guo: Conceptualization, project administration, funding acquisition, supervision, and writing – review & editing.
Declaration of competing interest
The authors declare that there are no conflicts of interest.
| [1] |
GBD 2019 Mental Disorders Collaborators . Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990‒2019: a systematic analysis for the global burden of disease study 2019. Lancet Psychiatry. 2022; 9(2): 137-150.
|
| [2] |
2024 Alzheimer's disease facts and figures. Alzheimer's Dement. 2024; 20(5): 3708-3821.
|
| [3] |
Lu J, Xu X, Huang Y, et al. Prevalence of depressive disorders and treatment in China: a cross—sectional epidemiological study. Lancet Psychiatry. 2021; 8(11): 981-990.
|
| [4] |
Cheng J, Xue F, Zhang Y, Ji J, Liu T . Current status, key technologies, and countermeasures in the research and development of medicinal and edible products. J Nanjing Univ Tradit Chin Med. 2023; 39(9): 814-826.
|
| [5] |
Sun XY, Sun FY . Shengnong's Herbals. Taiyuan, China: Shanxi Science and Technology Press; 2018 [Chinese].
|
| [6] |
Sahin S, Bayindir N, Ertas B, et al. The therapeutic role of ginseng in promoting hippocampal neurogenesis and ameliorating cognitive function following whole brain radiotherapy in rats. Metab Brain Dis. 2025; 40(8): 303.
|
| [7] |
Hwang J, Keum M, Choe YM, et al. Panax ginseng: a modulator of amyloid, tau pathology, and cognitive function in Alzheimer's disease . J Ginseng Res. 2025; 49(4): 348-355.
|
| [8] |
Hedayati—Moghadam M, Seyedi F, Eftekhari H, Dalfardi M, Baghcheghi Y . Exploring the neurological pathways of P. ginseng memory—enhancing effects . J Complement Integr Med. 2025. https://doi.org/10.1515/jcim—2025—0169. Epub ahead of print.
|
| [9] |
Tan X, Gu J, Zhao B, et al. Ginseng improves cognitive deficit via the RAGE/NF—κB pathway in advanced glycation end product—induced rats. J Ginseng Res. 2015; 39(2): 116-124.
|
| [10] |
Lee BC, Choe YM, Suh GH, et al. Ginseng intake and Alzheimer disease—specific cognition in older adults according to apolipoprotein ε4 allele status. Front Aging Neurosci. 2023; 15: 1152626.
|
| [11] |
Lee M, Lee SH, Kim MS, Ahn KS, Kim M . Effect of Lactobacillus dominance modified by Korean red ginseng on the improvement of Alzheimer's disease in mice . J Ginseng Res. 2022; 46(3): 464-472.
|
| [12] |
Shin YJ, Lee DY, Kim JY, et al. Effect of fermented red ginseng on gut microbiota dysbiosis— or immobilization stress—induced anxiety, depression, and colitis in mice. J Ginseng Res. 2023; 47(2): 255-264.
|
| [13] |
Shin SJ, Jeon SG, Kim JI, et al. Red ginseng attenuates aβ—induced mitochondrial dysfunction and aβ—mediated pathology in an animal model of Alzheimer's disease. Int J Mol Sci. 2019; 20(12): 3030.
|
| [14] |
Ju S, Seo JY, Lee SK, Oh J, Kim JS . Oral administration of hydrolyzed red ginseng extract improves learning and memory capability of scopolamine—treated C57BL/6J mice via upregulation of Nrf2—mediated antioxidant mechanism. J Ginseng Res. 2021; 45(1): 108-118.
|
| [15] |
Lim C, Kim JH, Lim S, Seo M, Cho S . Methanolic extract of Korean red ginseng attenuates NLRP3 inflammasome—mediated neuroinflammation in chronic cerebral hypoperfusion—induced cognitive impairment: a comparative study. Fitoterapia. 2025; 185: 106734.
|
| [16] |
Han SK, Joo MK, Kim JK, Jeung W, Kang H, Kim DH . Bifidobacteria—fermented red ginseng and its constituents ginsenoside Rd and protopanaxatriol alleviate anxiety/depression in mice by the amelioration of gut dysbiosis. Nutrients. 2020; 12(4): 901.
|
| [17] |
Bui BP, Nguyen PL, Do HTT, Cho J . Anxiolytic effect of Korean red ginseng through upregulation of serotonin and GABA transmission and BDNF expression in immobilized mice. J Ginseng Res. 2022; 46(6): 819-829.
|
| [18] |
Lee B, Sur B, Lee H, Oh S . Korean red ginseng prevents posttraumatic stress disorder—triggered depression—like behaviors in rats via activation of the serotonergic system. J Ginseng Res. 2020; 44(4): 644-654.
|
| [19] |
Zheng QL, Zhu HY, Xu X, et al. Korean red ginseng alleviate depressive disorder by improving astrocyte gap junction function. J Ethnopharmacol. 2021; 281: 114466.
|
| [20] |
Lee BR, Lee JH, Ko YH, et al. Korean red ginseng reduces chronic social defeat stress—induced mood disorders via N—methyl—D—aspartate receptor modulation in mice. J Ginseng Res. 2021; 45(2): 254-263.
|
| [21] |
Sung SJ, Lee BR, Ko YH, Lee SY, Jang CG . Korean red ginseng extract mitigates CSDS—induced mood disorders by modulating NMDA receptor. IBRO Rep. 2019; 6: S248-S249.
|
| [22] |
Dormal V, Jonniaux L, Buchet M, Simar L, Copine S, Deldicque L . 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. 2025; 17(6): 955.
|
| [23] |
Lee KH, Bahk WM, Lee SJ, Pae CU . Effectiveness and tolerability of Korean red ginseng augmentation in major depressive disorder patients with difficult—to—treat in routine practice. Clin Psychopharmacol Neurosci. 2020; 18(4): 621-626.
|
| [24] |
Ha Y, Jo HS, Kwon TW, et al. Korean black ginseng extract alleviates Alzheimer's disease—related cognitive impairment by activating the Nrf2/HO—1 pathway and suppressing the p38 MAPK/NF—κB/STAT3 pathways and NLRP3 inflammasome via TLR2 and TLR4 modulation. J Ginseng Res. 2025; 49(3): 294-305.
|
| [25] |
Shi ZY, Zeng JZ, Wong AST . Chemical structures and pharmacological profiles of ginseng saponins. Molecules. 2019; 24(13): 2443.
|
| [26] |
Mou N, Duan Z, Ma P, Fu R, Fan D . Study on the hypnotic effect of rare protopanaxadiol—type and protopanaxatriol—type ginsenosides. RSC Adv. 2019; 9(35): 20483-20491.
|
| [27] |
Sharma A, Lee HJ . Ginsenoside compound K: insights into recent studies on pharmacokinetics and health—promoting activities. Biomolecules. 2020; 10(7): 1028.
|
| [28] |
Qin W, Chen F, Li Q, et al. Target identification of ginsenosides against cognitive impairment by using mass spectrometry—based cellular thermal shift assay (CETSA). Neurochem Res. 2025; 50(3): 156.
|
| [29] |
Tian Z, Ren N, Wang J, Zhang D, Zhou Y . Ginsenoside ameliorates cognitive dysfunction in type 2 diabetic goto—kakizaki rats. Med Sci Monit. 2018; 24: 3922-3928.
|
| [30] |
Feng H, Xue M, Deng H, Cheng S, Hu Y, Zhou C . Ginsenoside and its therapeutic potential for cognitive impairment. Biomolecules. 2022; 12(9): 1310.
|
| [31] |
He S, Shi J, Chai H, et al. Mechanisms with network pharmacology approach of ginsenosides in Alzheimer's disease. Heliyon. 2024; 10(5): e26642.
|
| [32] |
Kim HJ, Jung SW, Kim SY, et al. Panax Ginseng as an adjuvant treatment for Alzheimer's disease . J Ginseng Res. 2018; 42(4): 401-411.
|
| [33] |
Lee R, Lee HS, Kim WW, Kim M, Nah SY . Cognitive function improvement effects of gintonin—enriched fraction in subjective memory impairment: an assessor— and participant—blinded placebo—controlled study. J Ginseng Res. 2023; 47(6): 735-742.
|
| [34] |
Fan X, Tian C, Sun F . Effects of ginsenoside CK on postoperative cognitive function in rats. J Clin Anesth. 2025; 41(7): 743-747 [Chinese].
|
| [35] |
Li XT, Meng Y, Wei L, et al. Effect of ginsenoside CK on cognitive dysfunction and hippocampal NLRP3 inflammasome in mice with Alzheimer's disease induced by Aβ. J Chin Med Mater. 2021; 44(8): 1942-1945 [Chinese].
|
| [36] |
Fan X, Tian C, Su F . Effects of ginsenoside CK on postoperative cognitive function and mitochondrial function in rats. J Clin Anesth. 2025; 41(10): 1098-1102 [Chinese].
|
| [37] |
Li N, Fang X, Li H, et al. Ginsenoside CK modulates glucose metabolism via PPARγ to ameliorate SCOP—induced cognitive dysfunction. Metab Brain Dis. 2025; 40(4): 168.
|
| [38] |
Yan X, Bai X, Fu R, Duan Z, Zeng W, Zhu C . Ginsenoside compound K alleviates D—galactose—induced mild cognitive impairment by modulating gut microbiota—mediated short—chain fatty acid metabolism. Food Funct. 2024; 15(18): 9037-9052.
|
| [39] |
Li W, Kong Z, Yang L, et al. Ginsenoside compound K ameliorates depressive—like behaviors by targeting kynurenine 3—monooxygenase. Phytomedicine. 2025; 148: 157335.
|
| [40] |
Liu Y, Zong X, Huang J, et al. Ginsenoside Rb1 regulates prefrontal cortical GABAergic transmission in MPTP—treated mice. Aging. 2019; 11(14): 5008-5034.
|
| [41] |
Wang Y, Li Y, Yang W, et al. Ginsenoside Rb1 inhibit apoptosis in rat model of Alzheimer's disease induced by Aβ1—40. Am J Transl Res. 2018; 10(3): 796-805.
|
| [42] |
Zhou B, Wu L, Liu D, et al. Ginsenoside Rb1 attenuates age—associated cognitive impairment by modulating oxidative stress and the SIRT1/ENOS/NO axis. J Ginseng Res. 2025; 49(6): 683-691.
|
| [43] |
Lin SB . Effect of ginsenoside Rb1 postconditioning on cognitive function after global cerebral ischemia reperfusion in rats. Strait Pharm J. 2017; 29(7): 15-17 [Chinese].
|
| [44] |
Jiang N, Wang K, Zhang Y, et al. Protective effect of ginsenoside Rb1 against chronic restraint stress (CRS)—induced memory impairments in rats. Behav Brain Res. 2021; 405: 113146.
|
| [45] |
Guo Y, Xie J, Zhang L, et al. Ginsenoside Rb1 exerts antidepressant—like effects via suppression inflammation and activation of AKT pathway. Neurosci Lett. 2021; 744: 135561.
|
| [46] |
Lu YY, Zhu MJ, Ni LN, et al. Establishment of CUMS + LPS induced depression model in mice and antidepressant mechanism research of ginsenoside Rb1. J Yantai Univ Nat Sci Eng Ed. 2019; 32(2): 146-150 [Chinese].
|
| [47] |
Wang GL, Wang YP, Zheng JY, Zhang LX . Monoaminergic and aminoacidergic receptors are involved in the antidepressant—like effect of ginsenoside Rb1 in mouse hippocampus (CA3) and prefrontal cortex. Brain Res. 2018; 1699: 44-53.
|
| [48] |
Lee B, Sur B, Cho SG, et al. Ginsenoside Rb1 rescues anxiety—like responses in a rat model of post—traumatic stress disorder. J Nat Med. 2016; 70(2): 133-144.
|
| [49] |
Zhao Y, Song T, Ren P, et al. Integrating metagenomics, lipidomics and proteomics to explore the effect and mechanism of ginsenoside Rb1 on atherosclerosis co—depression disease. Phytomedicine. 2025; 148: 157301.
|
| [50] |
Zhang Y, Yang X, Wang S, Song S . Ginsenoside Rg3 prevents cognitive impairment by improving mitochondrial dysfunction in the rat model of Alzheimer's disease. J Agric Food Chem. 2019; 67(36): 10048-10058.
|
| [51] |
Zhu S, Jiang T, Zhang HC, et al. Effects of ginsenoside Rg3 on behavioral patterns in UVB—induced depression model rats. Chin Tradit Pat Med. 2021; 43(11): 3143-3147 [Chinese].
|
| [52] |
Kang A, Xie T, Zhu D, Shan J, Di L, Zheng X . Suppressive effect of ginsenoside Rg3 against lipopolysaccharide—induced depression—like behavior and neuroinflammation in mice. J Agric Food Chem. 2017; 65(32): 6861-6869.
|
| [53] |
Yu T, Chen D, Wang D, Zhu G, Gao Q . Network pharmacology—based study on the mechanism of ginseng in anti—depression. Acad J Shanghai Univ Tradit Chin Med. 2021; 35(1): 74-82 [Chinese].
|
| [54] |
Fang L, Yang L . Therapeutic effect and mechanism of ginsenoside Rh2 on mice with chronic unpredictable stress—induced depression. Zhejiang Med. 2019; 41(21): 2269—2273, 2352 [Chinese].
|
| [55] |
Guan W, Jin X, Yang Y . Ginsenoside Rh2 reduced neurogenesis dysfunction to alleviate depression—like behaviour in CSDS—induced mice. Nat Prod J. 2025; 15(2): e060524229698.
|
| [56] |
Shi LS, Ji CH, Liu Y, et al. Ginsenoside Rh2 administration produces crucial antidepressant—like effects in a CUMS—induced mice model of depression. Brain Behav. 2022; 12(8): e2705.
|
| [57] |
Wu Y, Zhang Z, Lian X . Ginsenoside Rc mitigates hippocampal neuronal damage and cognitive impairment in vascular dementia rats via the pY705—Stat3/Foxo3a and pS727—Stat3/GRIM—19 pathways. J Ginseng Res. 2025; 49(6): 702-713.
|
| [58] |
Wang H, Jiang N, Lv J, Huang H, Liu X . Ginsenoside Rd reverses cognitive deficits by modulating BDNF—dependent CREB pathway in chronic restraint stress mice. Life Sci. 2020; 258: 118107.
|
| [59] |
Wan Q, Ma X, Zhang ZJ, et al. Ginsenoside reduces cognitive impairment during chronic cerebral hypoperfusion through brain—derived neurotrophic factor regulated by epigenetic modulation. Mol Neurobiol. 2017; 54(4): 2889-2900.
|
| [60] |
Liu Y, Duan H, Lv X, et al. Effects of ginsenoside Rd injection combined with alteplase on cognitive function and related factors in patients with acute ischemic cerebral stroke. Hebei Med J. 2020; 42(2): 268-271 [Chinese].
|
| [61] |
Chen H, Piao J, Geng Z, et al. Ginsenoside Rd alleviates LPS—induced neuroinflammation and depressive—like behaviors via regulating TLR4—PI3K—NF—κB—JMJD3 signaling. Int Immunopharmacol. 2025; 162: 115071.
|
| [62] |
Jiang N, Yao C, Zhang Y, Sun X, Choudhary MI, Liu X . Ginsenoside Rg1 attenuates chronic sleep deprivation—induced hippocampal mitochondrial dysfunction and improves memory by the AMPK—SIRT3 pathway. J Agric Food Chem. 2024; 72(4): 2362-2373.
|
| [63] |
Zhang Y, Liu S, Cao D, Zhao M, Lu H, Wang P . Rg1 improves Alzheimer's disease by regulating mitochondrial dynamics mediated by the AMPK/Drp1 signaling pathway. J Ethnopharmacol. 2025; 340: 119285.
|
| [64] |
Li X, Huang L, Kong L, et al. Ginsenoside Rg1 alleviates learning and memory impairments and Aβ disposition through inhibiting NLRP1 inflammasome and autophagy dysfunction in APP/PS1 mice. Mol Med Rep. 2022; 27: 6.
|
| [65] |
Chen L, Yao H, Chen X, et al. Ginsenoside Rg1 decreases oxidative stress and down—regulates Akt/mTOR signalling to attenuate cognitive impairment in mice and senescence of neural stem cells induced by d—galactose. Neurochem Res. 2018; 43(2): 430-440.
|
| [66] |
Kong L, Liu Y, Li J, et al. Ginsenoside Rg1 alleviates chronic inflammation—induced neuronal ferroptosis and cognitive impairments via regulation of AIM2—Nrf2 signaling pathway. J Ethnopharmacol. 2024; 330: 118205.
|
| [67] |
Shi DD, Huang YH, Lai CSW, et al. Ginsenoside Rg1 prevents chemotherapy—induced cognitive impairment: associations with microglia—mediated cytokines, neuroinflammation, and neuroplasticity. Mol Neurobiol. 2019; 56(8): 5626-5642.
|
| [68] |
Liang HY, Zhang PP, Zhang XL, et al. Preclinical systematic review of ginsenoside Rg1 for cognitive impairment in Alzheimer's disease. Aging. 2021; 13(5): 7549-7569.
|
| [69] |
Jing X, Zhao Y, Wang G, Tian W . Ginsenoside 1 mitigates postoperative cognitive dysfunction by enhancing microglial Aβ clearance through the endo—lysosomal pathway. Int Immunopharmacol. 2025; 150: 114281.
|
| [70] |
Zhong SJ, Wang L, Gu RZ, Zhang WH, Lan R, Qin XY . Ginsenoside Rg1 ameliorates the cognitive deficits in D—galactose and AlCl3—induced aging mice by restoring FGF2—Akt and BDNF—TrkB signaling axis to inhibit apoptosis. Int J Med Sci. 2020; 17(8): 1048-1055.
|
| [71] |
Jiang N, Lv J, Zhang Y, et al. Protective effects of ginsenosides Rg1 and Rb1 against cognitive impairment induced by simulated microgravity in rats. Front Pharmacol. 2023; 14: 1167398.
|
| [72] |
Liu Y, You PF, Cheng F, et al. Effect of ginsenoside Rg1 on cognitive impairment induced by low temperature in mice. Trauma Crit Care Med. 2024; 12(5): 263-266 [Chinese].
|
| [73] |
Sun Y, Yang Y, Liu S, et al. New therapeutic approaches to and mechanisms of ginsenoside Rg1 against neurological diseases. Cells. 2022; 11(16): 2529.
|
| [74] |
Wu JJ, Yang Y, Wan Y, et al. New insights into the role and mechanisms of ginsenoside Rg1 in the management of Alzheimer's disease. Biomed Pharmacother. 2022; 152: 113207.
|
| [75] |
Huang L, Peng Z, Lu C, et al. Ginsenoside Rg1 alleviates repeated alcohol exposure—induced psychomotor and cognitive deficits. Chin Med. 2020; 15(1): 44.
|
| [76] |
Jin Y, Peng J, Wang X, Zhang D, Wang T . Ameliorative effect of ginsenoside Rg1 on lipopolysaccharide—induced cognitive impairment: role of cholinergic system. Neurochem Res. 2017; 42(5): 1299-1307.
|
| [77] |
Dong X, Kong L, Huang L, et al. Ginsenoside Rg1 treatment protects against cognitive dysfunction via inhibiting PLC—CN—NFAT1 signaling in T2DM mice. J Ginseng Res. 2023; 47(3): 458-468.
|
| [78] |
Wu JJ, Zhang L, Liu D, et al. Ginsenoside Rg1, lights up the way for the potential prevention of Alzheimer's disease due to its therapeutic effects on the drug—controllable risk factors of Alzheimer's disease. J Ethnopharmacol. 2024; 318: 116955.
|
| [79] |
Guo YH, Xia ZY, Chen J, Xia ZR . Effect of ginsenoside Rg1 on expression of glutamate and its receptor in chronic stress depression model rats. Chin Hosp Pharm J. 2019; 39(2): 137-141 [Chinese].
|
| [80] |
Han D, Zhao Z, Mao T, Gao M, Yang X, Gao Y . Ginsenoside Rg1: a neuroprotective natural dammarane—type triterpenoid saponin with anti—depressive properties. CNS Neurosci Ther. 2024; 30(12): e70150.
|
| [81] |
Wang J, Shen F, Zhang Z, Zhu G . Effects of ginsenoside Rg1 on depression—like behaviors, expression of hippocampal synaptic proteins and activation of glial cells in stressed mice. J Biol. 2021; 38(3): 26-30 [Chinese].
|
| [82] |
Li J, Gao W, Zhao Z, et al. Ginsenoside Rg1 reduced microglial activation and mitochondrial dysfunction to alleviate depression—like behaviour via the GAS5/EZH2/SOCS3/NRF2 axis. Mol Neurobiol. 2022; 59(5): 2855-2873.
|
| [83] |
Bei X, Jiang N, Yao C, et al. Effects and comparison of ginsenosides Rg1 and Rb1 in depression— and anxiety—like behaviors induced by chronic unpredictable stress in rats. Chin J Comp Med. 2024; 34(7): 68-78 [Chinese].
|
| [84] |
Wang YF, Zhu MJ, Li MM, et al. Ameliorative effects of ginsenoside Rg1 on CUMS + LPS induced depressive—like behavior and its mechanisms in mice. J Yantai Univ Nat Sci Eng Ed. 2021; 34(3): 308-314, 347 [Chinese].
|
| [85] |
Wang WF, Chu SF, Chen NH . Ginsenoside Rg1 exerts antidepressant effects through anti—inflammatory and antioxidant actions. Acta Neuropharmacol. 2025; 15(5): 63 [Chinese].
|
| [86] |
Zhang H, Huang N, Ma XX, Zhu M, Liu YN . Effects of ginsenoside Rg1 on depressive behavior, hippocampal neuron damage, PKA, and PKC in rats with depression. Prog Mod Biomed. 2023; 23(16): 3027-3031 [Chinese].
|
| [87] |
Mou Z, Huang Q, Chu SF, et al. Antidepressive effects of ginsenoside Rg1 via regulation of HPA and HPG axis. Biomed Pharmacother. 2017; 92: 962-971.
|
| [88] |
Lu C, Shi Z, Dong L, et al. Exploring the effect of ginsenoside Rh1 in a sleep deprivation—induced mouse memory impairment model. Phytother Res. 2017; 31(5): 763-770.
|
| [89] |
Bi YF, Tao WM, Wang XZ, et al. Effect of ginsenoside Rh1 on cognitive impairment in mice. Sci Technol Food Ind. 2019; 40(24): 300-304 [Chinese].
|
| [90] |
Kim Y, Lee HY, Choi YJ, Cho SH . Antidepressant effects of ginsenoside Rf on behavioral change in the glial degeneration model of depression by reversing glial loss. J Ginseng Res. 2020; 44(4): 603-610.
|
| [91] |
Nguyen BT, Shin EJ, Jeong JH, et al. Ginsenoside Re attenuates memory impairments in aged Klotho deficient mice via interactive modulations of angiotensin II AT1 receptor, Nrf2 and GPx—1 gene . Free Radic Biol Med. 2022; 189: 2-19.
|
| [92] |
Li X, Sui DY, Li W . The effect of ginsenoside Re on improving scopolamine—induced cognitive impairment in mice. Ginseng Res. 2024; 36(6): 3-6 [Chinese].
|
| [93] |
Fan R. Improvement effect of ginsenoside on cognitive impairment of aging rats after sevoflurane anesthesia based in antiinflammatory and antioxidant effect. Guizhou Med J. 2021; 45(4): 507-509, 521 [Chinese].
|
| [94] |
Xu L, Wang W, Yang H, Lan Y . Effects of ginsenoside Re on depressive—like behavior of morphine withdrawal mice. J Med Sci Yanbian Univ. 2019; 42(2): 99-103 [Chinese].
|
| [95] |
Cui J, Shan R, Cao Y, Zhou Y, Liu C, Fan Y . Protective effects of ginsenoside Rg2 against memory impairment and neuronal death induced by Aβ25‒35 in rats. J Ethnopharmacol. 2021; 266: 113466.
|
| [96] |
Choi SY, Kim KJ, Song JH, Lee BY . Ginsenoside Rg5 prevents apoptosis by modulating heme—oxygenase—1/nuclear factor E2—related factor 2 signaling and alters the expression of cognitive impairment—associated genes in thermal stress—exposed HT22 cells. J Ginseng Res. 2018; 42(2): 225-228.
|
| [97] |
Wang Q, Dong L, Wang M, et al. Dammarane sapogenins improving simulated weightlessness—induced depressive—like behaviors and cognitive dysfunction in rats. Front Psychiatr. 2021; 12: 638328.
|
| [98] |
Jiang N, Zhang BY, Dong LM, et al. Antidepressant effects of dammarane sapogenins in chronic unpredictable mild stress—induced depressive mice. Phytother Res. 2018; 32(6): 1023-1029.
|
| [99] |
Li Z, Zhao L, Chen J, et al. Ginsenoside Rk1 alleviates LPS—induced depression—like behavior in mice by promoting BDNF and suppressing the neuroinflammatory response. Biochem Biophys Res Commun. 2020; 530(4): 658-664.
|
| [100] |
She L, Sun J, Xiong L, et al. Ginsenoside RK1 improves cognitive impairments and pathological changes in Alzheimer's disease via stimulation of the AMPK/Nrf2 signaling pathway. Phytomedicine. 2024; 122: 155168.
|
| [101] |
Yang XK, Ma XW, Shen L, Pei S, Nie ZH, Xiao XF . Antidepressant effect of secondary ginsenoside H dripping pills on chronic unpredictable mild stress rats. Drugs Clin. 2017; 32(7): 1177-1183 [Chinese].
|
| [102] |
Bao Y, Chen Y, Zeng GR, Yang ZY, Pan RL, Shi Z . Protective effect of total ginsenoside ginseng root on learning and memory impairment and anxiety in rats induced by hindlimb suspension. Chin J Exp Tradit Med Formulae. 2021; 27(7): 49-56 [Chinese].
|
| [103] |
Wang J, Wang D, Zhou Z, et al. Saponins from Panax japonicus alleviate HFD—induced impaired behaviors through inhibiting NLRP3 inflammasome to upregulate AMPA receptors. Neurochem Int. 2021; 148: 105098.
|
| [104] |
Irshad H, Qian JJ, Zhang WN, et al. Study of the antidepressant—like effects of ginseng pectin acidic fractions via regulation of the BDNF/TrkB signaling pathway. Lishizhen Med Mater Med Res. 2016; 27(7): 1551-1554 [Chinese].
|
| [105] |
Kim S, Shin SJ, Nam Y, et al. Korean red ginseng polysaccharide as a potential therapeutic agent targeting tau pathology in Alzheimer's disease. Int J Biol Macromol. 2024; 263: 130516.
|
| [106] |
Shin SJ, Nam Y, Park YH, et al. Therapeutic effects of non—saponin fraction with rich polysaccharide from Korean red ginseng on aging and Alzheimer's disease. Free Radic Biol Med . 2021; 164: 233-248.
|
| [107] |
Xu T, Shen X, Yu H, Sun L, Lin W, Zhang C . Water—soluble ginseng oligosaccharides protect against scopolamine—induced cognitive impairment by functioning as an antineuroinflammatory agent. J Ginseng Res. 2016; 40(3): 211-219.
|
| [108] |
Xu W, Yu P, Shao S, et al. Oligosaccharides from black ginseng innovatively prepared by low—temperature steam—heating process ameliorate cognitive impairment in Alzheimer's disease mice via the Keap—1/Nrf2 pathway. J Sci Food Agric. 2024; 104(9): 5625-5638.
|
| [109] |
Al—Hazmi MA, Rawi SM, Arafa NM, Wagas A, Montasser AO . The potent effects of ginseng root extract and memantine on cognitive dysfunction in male albino rats. Toxicol Ind Health. 2015; 31(6): 494-509.
|
| [110] |
Lu C, Lyu J, Dong L, et al. Neuroprotective effects of 20(S)—protopanaxatriol (PPT) on scopolamine—induced cognitive deficits in mice. Phytother Res. 2018; 32(6): 1056-1063.
|
| [111] |
Park CH, Park SK, Seung TW, Jin DE, Guo T, Heo HJ . Effect of ginseng (Panax ginseng) berry EtOAc fraction on cognitive impairment in C57BL/6 mice under high—fat diet inducement . Evid Based Complement Alternat Med. 2015; 2015: 316527.
|
| [112] |
Mando Z, Al Zarzour RH, Alshehade S, et al. Terpenoids and triterpenoid saponins: future treatment for depression. Curr Tradit Med. 2024; 10(2): e230223213965.
|
| [113] |
Park K, Kim R, Cho K, et al. Panaxcerol D from Panax ginseng ameliorates the memory impairment induced by cholinergic blockade or Aβ25‒35 peptide in mice . J Ginseng Res. 2024; 48(1): 59-67.
|
| [114] |
Li H, Song J, Zhang J, et al. Ginseng protein reverses amyloid beta peptide and H2O2 cytotoxicity in neurons, and ameliorates cognitive impairment in AD rats induced by a combination of D—galactose and AlCl3. Phytother Res. 2017; 31(2): 284-295.
|
| [115] |
Nam SM, Hwang H, Seo M, et al. Gintonin attenuates D—galactose—induced hippocampal senescence by improving long—term hippocampal potentiation, neurogenesis, and cognitive functions. Gerontology. 2018; 64(6): 562-575.
|
| [116] |
Wang W, Liu X, Liu J, et al. Sesquiterpenoids from the root of Panax ginseng attenuates lipopolysaccharide—induced depressive—like behavior through the brain—derived neurotrophic factor/tropomyosin—related kinase B and sirtuin type 1/nuclear factor—κB signaling pathways . J Agric Food Chem. 2018; 66(1): 265-271.
|
| [117] |
Hu Y, Xu B . Prediction of antidepressant mechanism of ginseng by network pharmacology. J Shaanxi Univ Chin Med. 2021; 44(5): 113-119 [Chinese].
|
| [118] |
Zhang W, Han Q, Xu C . Effect of 20(S)—protopanaxadiol on the ethology in the anxiety model mice and neurotransmitter and certain gene expression in its brain. Chin J Clin Pharm. 2015; 24(4): 220-227 [Chinese].
|
| [119] |
Terstege DJ, MacDonald DS, Tasker RA . Standardised ginseng extract G115 potentiates the antidepressant—like properties of fluoxetine in the forced swim test. Acta Neuropsychiatr. 2021; 33(3): 141-147.
|
| [120] |
Lai W, Lin S, Liu H, et al. Effects of ginseng on gut microbiota of LPS—induced depression—like behavior mice based on 16S rDNA sequencing technology. J Guangdong Pharm Univ. 2023; 39(4): 41-48 [Chinese].
|
| [121] |
Lee WJ, Shin YW, Chang H, et al. Safety and efficacy of dietary supplement (gintonin—enriched fraction from ginseng) in subjective memory impairment: a randomized placebo—controlled trial. Integr Med Res. 2022; 11(1): 100773.
|
| [122] |
Dong XZ, Wang DX, Zhang TY, Liu X, Liu P, Hu Y . Identification of protein targets for the antidepressant effects of Kai—Xin—San in Chinese medicine using isobaric tags for relative and absolute quantitation. Neural Regen Res. 2020; 15(2): 302-310.
|
| [123] |
Yao L, Jing R, Wang C, et al. Kai—Xin—San ameliorates fluoxetine—resistant depressive—like behaviors by modulating tryptophan—kynurenine metabolic homeostasis in a rodent model. J Ethnopharmacol. 2025; 351: 120011.
|
| [124] |
Jiang N, Wang H, Li C, et al. The antidepressant—like effects of the water extract of Panax ginseng and Polygala tenuifolia are mediated via the BDNF—TrkB signaling pathway and neurogenesis in the hippocampus . J Ethnopharmacol. 2021; 267: 113625.
|
| [125] |
Zhang H, Cao J, Zheng B, Liu Q, Liang K, Qiao T . Study on the antidepressant mechanism of ginseng—fragrant solomonseal rhizome couplet medicines on inhibiting the activation of inflammasomes NLRP1, NLRC4, and AIM2, and regulating the expression of inflammatory cytokines. J Beijing Univ Tradit Chin Med. 2024; 47(7): 939-947 [Chinese].
|
| [126] |
Chen H, Huang Q, Zhang S, et al. The Chinese herbal formula PAPZ ameliorates behavioral abnormalities in depressive mice. Nutrients. 2019; 11(4): 859.
|
| [127] |
Liao XX, Hu K, Xie XH, et al. Banxia Xiexin decoction alleviates AS co—depression disease by regulating the gut microbiome—lipid metabolic axis. J Ethnopharmacol. 2023; 313: 116468.
|
| [128] |
Liu A, Zhao Y, Sun Y, et al. Chaihu—Longgu—Muli decoction exerts antidepressant effects in rats by regulating the NLRP3 pathway. Pharmacol Res Mod Chin Med. 2025; 15: 100617.
|
| [129] |
Ma J, Wang F, Yang J, et al. Xiaochaihutang attenuates depressive/anxiety—like behaviors of social isolation—reared mice by regulating monoaminergic system, neurogenesis and BDNF expression. J Ethnopharmacol. 2017; 208: 94-104.
|
| [130] |
Zhang K, Wang Z, Pan X, Yang J, Wu C . Antidepressant—like effects of Xiaochaihutang in perimenopausal mice. J Ethnopharmacol. 2020; 248: 112318.
|
| [131] |
Zhang S, Hu Y, Zhao Y, et al. Molecular mechanism of Chang Shen Hua volatile oil modulating brain cAMP—PKA—CREB pathway to improve depression—like behavior in rats. Phytomedicine. 2024; 130: 155729.
|
| [132] |
Park HR, Cai M, Yang EJ . Herbal formula extract ameliorates anxiety and cognitive impairment via regulation of the reelin/dab—1 pathway in a murine model of post—traumatic stress disorder. Pharmaceutics. 2024; 16(9): 1150.
|
| [133] |
Li D, Xue A, Guan Y, Qiu Q, Ren Y, Zhang N . Investigation of Kai—Xin—San in alleviating cognitive impairment in aβ transgenic Caenorhabditis elegans through mitochondrial function regulation . Fitoterapia. 2025; 187: 106921.
|
| [134] |
Ren J, Xiang B, Song L, et al. Kaixinsan regulates neuronal mitochondrial homeostasis to improve the cognitive function of Alzheimer's disease by activating CaMKKβ—AMPK—PGC—1α signaling axis. Phytomedicine. 2024; 135: 156170.
|
| [135] |
Shan X, Lv S, Huang P, et al. Classic famous prescription Kai—Xin—San ameliorates Alzheimer's disease via the Wnt/β—catenin signaling pathway. Mol Neurobiol. 2024; 61(4): 2297-2312.
|
| [136] |
Xu YM, Wang XC, Xu TT, et al. Kai Xin San ameliorates scopolamine—induced cognitive dysfunction. Neural Regen Res. 2019; 14(5): 794-804.
|
| [137] |
Wang Q, Zhang YL, Li YH, et al. The memory enhancement effect of Kai Xin San on cognitive deficit induced by simulated weightlessness in rats. J Ethnopharmacol. 2016; 187: 9-16.
|
| [138] |
Ohsawa M, Tanaka Y, Ehara Y, Makita S, Onaka K . A possibility of simultaneous treatment with the multicomponent drug, Ninjin’yoeito, for anorexia, apathy, and cognitive dysfunction in frail Alzheimer's disease patients: an open—label pilot study. J Alzheimers Dis Rep. 2017; 1(1): 229-235.
|
| [139] |
Okahara K, Ohsawa M, Haruta—Tsukamoto A, et al. Frailty improvement by multicomponent drug, Ninjin'Yoeito, in mild cognitive impairment and mild Alzheimer's disease patients: an open—label exploratory study (FRAMINGO). J Alzheimers Dis Rep. 2023; 7(1): 107-117.
|
| [140] |
Yagi T, Sawada K, Miyamoto M, et al. Safety and efficacy of Ninjin’yoeito along with iron supplementation therapy for preoperative Anemia, fatigue, and anxiety in patients with gynecological disease: an open—label, single—center, randomized phase—II trial . BMC Womens Health. 2022; 22(1): 229.
|
| [141] |
Huang H, Lu W, Huang Y, et al. Bazi Bushen improves cognitive dysfunction in 5 × FAD mice by targeting amyloid pathology, neuroinflammation and cellular senescence. J Ethnopharmacol. 2026; 355: 120586.
|
| [142] |
Liu X, Ding H, Chen M, et al. Shenfu injection mediated NLRP3/caspase 1 through (R)—norcoclaurinee alleviates sepsis—induced cognitive dysfunction. J Inflamm Res. 2024; 17: 7295-7310.
|
| [143] |
Zhang WL, Chi YL, Wang LZ, Liu H, Zhao LX, Su F . Administrations of preoperative Shenmai injection and postoperative Shenfu injection, two ginseng containing TCM formulas, improve cognitive dysfunction in aged rats. Am J Chin Med. 2018; 46(5): 1065-1078.
|
| [144] |
Yi H, Zhang M, Miao J, Mu L, Hu C . Potential mechanisms of Shenmai injection against POCD based on network pharmacology and molecular docking. Int J Neurosci. 2024; 134(8): 931-942.
|
| [145] |
Chen L, Wang L, Zhuo Q, et al. Effect of Shenmai injection on cognitive function after cardiopulmonary bypass in cardiac surgical patients: a randomized controlled trial. BMC Anesthesiol. 2018; 18(1): 142.
|
| [146] |
Ren J, Wei D, An H, Zhang J, Zhang Z . Shenqi Yizhi granules protect hippocampus of AD transgenic mice by modulating on multiple pathological processes. J Ethnopharmacol. 2020; 263: 112869.
|
| [147] |
Zhong Y, Yao J, Sun C, Zhang G, Li F . Effect and mechanism of Ginseng Guben oral liquid on cognitive function of mice after femoral fracture operation. Chin Tradit Herb Drugs. 2022; 53(10): 3078-3083 [Chinese].
|
| [148] |
Liu JJ, Wei F, Wang YD, et al. Ginseng and Polygonum multiflorum formula protects brain function in Alzheimer's disease . Front Pharmacol. 2025; 16: 1461177.
|
| [149] |
Liu J, Chang D, Cordato D, et al. A pilot randomized controlled trial of WeiNaoKang (SaiLuoTong) in treating vascular dementia. Aging Med. 2022; 5(4): 246-256.
|
| [150] |
Sui H, Zhu L, Zhan L, Bi T, Zhang B . ZiBuPiYin recipe ameliorates diabetes—associated cognitive decline by improving neuronal mitochondrial function in chronic psychologically stressed zucker diabetic fatty rats. J Ethnopharmacol. 2023; 302: 115947.
|
| [151] |
Zhang Y, Yuan X, Zhang R, Shi L, Wang X, Liu JP . Effect of Renshen (Ginseng Radix et Rhizoma) and Zhimu (Anemarrhenae Rhizoma) on regulating NR2B—CaMKII—AMPAR1 pathway in prevention and treatment of diabetic cognitive dysfunction . J Liaoning Univ Tradit Chin Med. 2024; 26(4): 43-48 [Chinese].
|
| [152] |
He LL, Ai YT, Hu H . Exploring the mechanism of action of Ren Shen—Shi Chang Pu in treating mild cognitive impairment based on network pharmacology. Lishizhen Med Mater Med Res. 2021; 32(2): 276-280 [Chinese].
|
| [153] |
Li N, Liu C, Jing S, et al. Compound Schisandra—ginseng—notoginseng—lycium extract ameliorates scopolamine—induced learning and memory disorders in mice . Evid Based Complement Alternat Med. 2017; 2017: 8632016.
|
| [154] |
Liu Z, Qin G, Mana L, et al. GAPT regulates cholinergic dysfunction and oxidative stress in the brains of learning and memory impairment mice induced by scopolamine. Brain Behav. 2020; 10(5): e01602.
|
| [155] |
Tian D, Guo Y, Zhang D, et al. Shenzhi Jiannao formula ameliorates vascular dementia in vivo and in vitro by inhibition glutamate neurotoxicity via promoting clathrin—mediated endocytosis . Chin Med. 2021; 16(1): 65.
|
| [156] |
Ahmed A, Zeng G, Azhar M, et al. Jiawei Shengmai San herbal formula ameliorates diabetic associate cognitive decline by modulating AKT and CREB in rats. Phytother Res. 2020; 34(12): 3249-3261.
|
| [157] |
Seo YM, Choi SJ, Park CK, Gim MC, Shin DH . Synergistic effect of Korean red ginseng and Pueraria Montana var. Lobata against trimethyltin—induced cognitive impairment . Food Sci Biotechnol. 2018; 27(4): 1193-1200.
|
| [158] |
Jia C, Han S, Wei L, et al. Protective effect of compound Danshen (Salvia miltiorrhiza) dripping pills alone and in combination with carbamazepine on kainic acid—induced temporal lobe epilepsy and cognitive impairment in rats . Pharm Biol. 2018; 56(1): 217-224.
|
| [159] |
Zhu L, Zhu W, Zhu Q, Shang Y . Effects of modified Renshen Sini decoction combined with noninvasive ventilation on the function of hypothalamic—pituitary—thyroid (HPT) axis hormone level and cognitive function in AECOPD patients complicated with respiratory failure. J Emerg Tradit Chin Med. 2021; 30(12): 2182-2185 [Chinese].
|
| [160] |
Wang K, Yang R, Chen TT, Qin MR, Wang P, Kong MW . Therapeutic mechanism of Kai Xin San on Alzheimer's disease based on network pharmacology and experimental validation. Chin J Integr Med. 2023; 29(5): 413-423.
|
| [161] |
Wang J, Li C, Ruan J, et al. Cross—kingdom regulation of ginseng miRNA156 on immunity and metabolism. Int Immunopharmacol. 2024; 138: 112577.
|
| [162] |
Lee R, Kim JH, Kim WW, et al. Emerging evidence that ginseng components improve cognition in subjective memory impairment, mild cognitive impairment, and early Alzheimer's disease dementia. J Ginseng Res. 2024; 48(3): 245-252.
|
| [163] |
Allen J, Romay—Tallon R, Brymer KJ, Caruncho HJ, Kalynchuk LE . Mitochondria and mood: mitochondrial dysfunction as a key player in the manifestation of depression. Front Neurosci. 2018; 12: 386.
|
| [164] |
Ly M, Yu GZ, Mian A, et al. Neuroinflammation: a modifiable pathway linking obesity, Alzheimer's disease, and depression. Am J Geriatr Psychiatr. 2023; 31(10): 853-866.
|
| [165] |
Bazo—Alvarez JC, Morris TP, Carpenter JR, Hayes JF, Petersen I . Effects of long—term antipsychotics treatment on body weight: a population—based cohort study. J Psychopharmacol. 2020; 34(1): 79-85.
|
| [166] |
Kavirajan H, Schneider LS . Efficacy and adverse effects of cholinesterase inhibitors and memantine in vascular dementia: a meta—analysis of randomised controlled trials. Lancet Neurol. 2007; 6(9): 782-792.
|
| [167] |
Kim YS, Woo JY, Han CK, Chang IM . Safety analysis of Panax Ginseng in randomized clinical trials: a systematic review . Medicine. 2015; 2(2): 106-126.
|
| [168] |
Paik DJ, Lee CH . Review of cases of patient risk associated with ginseng abuse and misuse. J Ginseng Res. 2015; 39(2): 89-93.
|