DOI QR코드

DOI QR Code

Neuroprotective effect of Korean Red Ginseng against single prolonged stress-induced memory impairments and inflammation in the rat brain associated with BDNF expression

  • Lee, Bombi (Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University) ;
  • Sur, Bongjun (Department of Molecular Medicine and TIDRC, School of Medicine, Ewha Womans University) ;
  • Oh, Seikwan (Department of Molecular Medicine and TIDRC, School of Medicine, Ewha Womans University)
  • 투고 : 2021.06.01
  • 심사 : 2021.08.05
  • 발행 : 2022.05.01

초록

Background: Post-traumatic stress disorder (PTSD) is a psychiatric disease that develops following exposure to a traumatic event and is a stress-associated mental disorder characterized by an imbalance of neuroinflammation. Korean Red Ginseng (KRG) is the herbal supplement that is known to be involved in a variety of pharmacological activities. We aimed to investigate the effects of KRG on neuroinflammation as a potential mechanism involved in single prolonged stress (SPS) that negatively influences memory formation and consolidation and leads to cognitive and spatial impairment by regulating BDNF signaling, synaptic proteins, and the activation of NF-κB. Methods: We analyzed the cognitive and spatial memory, and inflammatory cytokine levels during the SPS procedure. SPS model rats were injected intraperitoneally with 20, 50, or 100 mg/kg/day KRG for 14 days. Results: KRG administration significantly attenuated the cognitive and spatial memory deficits, as well as the inflammatory reaction in the hippocampus associated with activation of NF-κB in the hippocampus induced by SPS. Moreover, the effects of KRG were equivalent to those exerted by paroxetine. In addition, KRG improved the expression of BDNF mRNA and the synaptic protein PSD-95 in the hippocampus. Taken together, these findings demonstrate that KRG exerts memory-improving actions by regulating anti-inflammatory activities and the NF-κB and neurotrophic pathway. Conclusion: Our findings suggest that KRG is a potential functional ingredient for protecting against memory deficits in mental diseases, such as PTSD.

키워드

과제정보

This research was supported by a grant from the Korean Society of Ginseng and the Korean Ginseng Cooperation (2020).

참고문헌

  1. Ceremuga TE, Shellabarger P, Persson T, Fanning M, Galey P, Robinson D, Bertsch S, Ceremuga GA, Bentley M. Effects of tetrahydropalmatine on posttraumatic stress disorder-induced changes in rat brain gene expression. J Integr Neurosci 2013;12:513-28. https://doi.org/10.1142/S0219635213500313
  2. Kessler RC. Posttraumatic stress disorder: the burden to the individual and to society. J Clin Psychiatr 2000;61:4-12.
  3. Hopper JW, Frewen PA, van der Kolk BA, Lanius RA. Neural correlates of reexperiencing, avoidance, and dissociation in PTSD: symptom dimensions and emotion dysregulation in responses to script-driven trauma imagery. J Trauma Stress 2007;20:713-25. https://doi.org/10.1002/jts.20284
  4. Leskin LP, White PM. Attentional networks reveal executive function deficits in posttraumatic stress disorder. Neuropsychology 007;21:275-284. https://doi.org/10.1037/0894-4105.21.3.275
  5. Han F, Xiao B, Wen L, Shi Y. Effects of fluoxetine on the amygdala and the hippocampus after administration of a single prolonged stress to male Wistar rates: in vivo proton magnetic resonance spectroscopy findings. Psychiatr Res 2015;232:154-61. https://doi.org/10.1016/j.pscychresns.2015.02.011
  6. Takahashi T, Morinobu S, Iwamoto Y, Yamawaki S. Effect of paroxetine on enhanced contextual fear induced by single prolonged stress in rats. Psychopharmacology 2006;189:165-73. https://doi.org/10.1007/s00213-006-0545-6
  7. Ebenezer PJ, Wilson CB, Wilson LD, Nair AR, Francis J. The Anti-Inflammatory Effects of Blueberries in an Animal Model of Post-Traumatic Stress Disorder (PTSD). PLoS One 2016;11:e0160923. https://doi.org/10.1371/journal.pone.0160923
  8. Wang SC, Lin CC, Chen CC, Tzeng NS, Liu YP. Effects of Oxytocin on Fear Memory and Neuroinflammation in a Rodent Model of Posttraumatic Stress Disorder. Int J Mol Sci 2018;19:3848 [Review]. https://doi.org/10.3390/ijms19123848
  9. Ebenezer PJ, Wilson CB, Wilson LD, Nair AR. The anti-inflammatory effects of blueberries in an animal model of post-traumatic stress disorder (PTSD). PloS One 2016;11:e0160923. https://doi.org/10.1371/journal.pone.0160923
  10. Wang SC, Lin CC, Chen CC, Tzeng NS, Liu YP. Effects of oxytocin on fear memory and neuroinflammation in a rodent model of posttraumatic stress disorder. Int J Mol Sci 2018a;19:3848-58. https://doi.org/10.3390/ijms19123848
  11. Lai S, Wu G, Jiang Z. Glycyrrhizin treatment facilitates extinction of conditioned fear responses after a single prolonged stress exposure in rats. Cell Physiol Biochem 2018;45:2529-39. https://doi.org/10.1159/000488271
  12. Liu M, Xie J, Sun Y. TLR4/MyD88/NF-kappaB-Mediated inflammation contributes to cardiac dysfunction in rats of PTSD. Cell Mol Neurobiol 2020;40:1029-35. https://doi.org/10.1007/s10571-020-00791-9
  13. Cunningham C, Hennessy E. Co-morbidity and systemic inflammation as drivers of cognitive decline: new experimental models adopting a broader paradigm in dementia research. Alzheimer's Res Ther 2015;7:33-40. https://doi.org/10.1186/s13195-015-0117-2
  14. Li XM, Han F, Liu DJ, Shi YX. Single-prolonged stress induced mitochondrial-dependent apoptosis in hippocampus in the rat model of post-traumatic stress disorder. J Chem Neuroanat 2010;40:248-55. https://doi.org/10.1016/j.jchemneu.2010.07.001
  15. Wang W, Wang R, Xu J, Qin X, Jiang H, Khalid A, Liu D, Pan F, Ho CSH, Ho RCM. Minocycline attenuates stress-induced behavioral changes via its anti-inflammatory effects in an animal model of post-traumatic stress disorder. Front Psychiatr 2018b;9:558-68. https://doi.org/10.3389/fpsyt.2018.00558
  16. Oh JY, Kim YK, Kim SN, Lee B, Jang JH, Kwon S, Park HJ. Acupuncture modulates stress response by the mTOR signaling pathway in a rat post-traumatic stress disorder model. Sci Rep 2018;8:11864-74. https://doi.org/10.1038/s41598-018-30337-5
  17. Li M, Xie Y, Niu K, Li K. Electroacupuncture ameliorates post-traumatic stress disorder in rats via a mechanism involving the BDNF-TrkB signaling pathway. Cell Mol Biol 2020;66:165-70.
  18. Dias L, Lopes CR, Goncalves FQ, Nunes A, Pochmann D, Machado NJ, Tome AR, Agostinho P, Cunha RA. Crosstalk between ATP-P 2X7 and adenosine A 2A receptors controlling neuroinflammation in rats subject to repeated restraint stress. Front Cell Neurosci 2021;1:639322-63932.
  19. 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;44:644-54. https://doi.org/10.1016/j.jgr.2019.09.005
  20. Kim S, Lee Y, Cho J. Korean red ginseng extract exhibits neuroprotective effects through inhibition of apoptotic cell death. Biol Pharm Bull 2014;37:938-46. https://doi.org/10.1248/bpb.b13-00880
  21. Lee J, Cho JY, Kim WK. Anti-inflammation effect of Exercise and Korean red ginseng in aging model rats with diet-induced atherosclerosis. Nutr Res Pract 2014;8:284-91. https://doi.org/10.4162/nrp.2014.8.3.284
  22. Park JK, Shim JY, Cho AR, Cho MR, Lee YJ. Korean red ginseng protects against mitochondrial damage and intracellular inflammation in an animal model of type 2 diabetes mellitus. J Med Food 2018;21:544-50. https://doi.org/10.1089/jmf.2017.4059
  23. Jin SH, Park JK, Nam KY, Park SN, Jung NP. Korean red ginseng saponins with low ratios of protopanaxadiol and protopanaxatriol saponin improve scopolamine-induced learning disability and spatial working memory in mice. J Ethnopharmacol 1999;66:123-9. https://doi.org/10.1016/S0378-8741(98)00190-1
  24. Serova LI, Laukova M, Alaluf LG, Pucillo L, Sabban EL. Intranasal neuropeptide Y reverses anxiety and depressive-like behavior impaired by single prolonged stress PTSD model. Eur Neuropsychopharmacol 2014;24:142-7. https://doi.org/10.1016/j.euroneuro.2013.11.007
  25. Lee S, Youn K, Jun M. Major compounds of red ginseng oil attenuate Abeta(25-35)-induced neuronal apoptosis and inflammation by modulating MAPK/NF-kappaB pathway. Food Funct 2018;9:4122-34. https://doi.org/10.1039/c8fo00795k
  26. Park S, Kim CS, Min J, Lee SH, Jung YS. A high-fat diet increases oxidative renal injury and protein glycation in D-galactose-induced aging rats and its prevention by Korea red ginseng. J Nutr Sci Vitaminol 2014;60:159-66. https://doi.org/10.3177/jnsv.60.159
  27. Sun K, Wang CS, Guo J, Horie Y, Fang SP, Wang F, Liu YY, Liu LY, Yang JY, Fan JY, Han JY. Protective effects of ginsenoside Rb1, ginsenoside Rg1, and notoginsenoside R1 on lipopolysaccharide-induced microcirculatory disturbance in rat mesentery. Life Sci 2007;81:509-18. https://doi.org/10.1016/j.lfs.2007.06.008
  28. Lee B, Hong R, Lim P, Cho D, Yeom M, Lee S, Kang KS, Lee SC, Shim I, Lee H, Hahm DH. The ethanolic extract of Aralia continentalis ameliorates cognitive deficits via modifications of BDNF expression and anti-inflammatory effects in a rat model of post-traumatic stress disorder. BMC Compl Alternative Med 2019;19:11-20. https://doi.org/10.1186/s12906-018-2417-0
  29. Hajipour S, Farbood Y, Gharib-Naseri MK, Goudarzi G, Rashno M, Maleki H, Bakhtiari N, Nesari A, Khoshnam SE, Dianat M, Sarkaki B, Sarkaki A. Exposure to ambient dusty particulate matter impairs spatial memory and hippocampal LTP by increasing brain inflammation and oxidative stress in rats. Life Sci 2020;242:117210-20. https://doi.org/10.1016/j.lfs.2019.117210
  30. Olsson A, Csajbok L, Ost M, Hoglund K, Nylen K, Rosengren L, Nellgard B, Blennow K. Marked increase of beta-amyloid(1-42) and amyloid precursor protein in ventricular cerebrospinal fluid after severe traumatic brain injury. J Neurol 2004;251:870-6.
  31. Gong QH, Pan LL, Liu XH, Wang Q, Huang H, Zhu YZ. S-propargyl-cysteine (ZYZ-802), a sulphur-containing amino acid, attenuates beta-amyloid-induced cognitive deficits and pro-inflammatory response: involvement of ERK1/2 and NF-kB pathway in rats. Amino Acids 2011;40:601-10. https://doi.org/10.1007/s00726-010-0685-1
  32. Yamada K, Mizuno M, Nabeshima T. Role for brain-derived neurotrophic factor in learning and memory. Life Sci 2002;70:735-44. https://doi.org/10.1016/S0024-3205(01)01461-8
  33. Mulati A, Ma S, Zhang H, Ren B, Zhao B, Wang L, Liu X, Zhao T, Kamanova S, Sair AT, Liu Z, Liu X. Sea-buckthorn flavonoids alleviate high-fat and high-fructose diet-induced cognitive impairment by inhibiting insulin resistance and neuroinflammation. J Agric Food Chem 2020;68:5835-46. https://doi.org/10.1021/acs.jafc.0c00876
  34. Ni L, Xu Y, Dong S, Kong Y, Wang H, Lu G, Wang Y, Li Q, Li C, Du Z, Sun H, Sun L. The potential role of the HCN1 ion channel and BDNF-mTOR signaling pathways and synaptic transmission in the alleviation of PTSD. Transl Psychiatry 2020;10:101-10. https://doi.org/10.1038/s41398-020-0782-1
  35. Barrientos RM, Sprunger DB, Campeau S, Watkins LR, Rudy JW, Maier SF. BDNF mRNA expression in rat hippocampus following contextual learning is blocked by intrahippocampal IL-1 beta administration. J Neuroimmunol 2004;155:119-26. https://doi.org/10.1016/j.jneuroim.2004.06.009
  36. Guan Z, Fang J. Peripheral immune activation by lipopolysaccharide decreases neurotrophins in the cortex and hippocampus in rats. Brain Behav Immun 2006;20:64-71. https://doi.org/10.1016/j.bbi.2005.04.005
  37. Ji LL, Peng JB, Fu CH, Cao D, Li D, Tong L, Wang ZY. Activation of Sigma-1 receptor ameliorates anxiety-like behavior and cognitive impairments in a rat model of post-traumatic stress disorder. Behav Brain Res 2016;311:408-15. https://doi.org/10.1016/j.bbr.2016.05.056