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Anti-neuroinflammatory Effects of Hwanggeumjakyak-tang on Lipopolysaccharide-induced Brain Injury Model in vivo and in vitro

지질다당류로 유발한 염증성 뇌손상 동물모델에 대한 황금작약탕의 억제효과 연구

  • Kim, Jong-gyu (Department of Korean Medicine Rehabilitation, College of Korean Medicine, Wonkwang University) ;
  • Im, Ji-sung (Department of Korean Medicine Rehabilitation, College of Korean Medicine, Wonkwang University) ;
  • An, Sung-Hu (Department of Korean Medicine Rehabilitation, Gwangju Medical Center, College of Korean Medicine, Wonkwang University) ;
  • Song, Yung-sun (Department of Third Medicine of Korean Medicine, Professional Graduate School of Oriental Medicine, Wonkwang University)
  • 김종규 (원광대학교 한의과대학 한방재활의학교실) ;
  • 임지성 (원광대학교 한의과대학 한방재활의학교실) ;
  • 안성후 (원광대학교 한의과대학 광주한방병원 한방재활의학과) ;
  • 송용선 (원광대학교 한의학전문대학원 제3의학과)
  • Received : 2021.09.06
  • Accepted : 2021.09.27
  • Published : 2021.10.31

Abstract

Objectives Hwanggeumjakyak-tang (HJT) has traditionally been used to treat gastrointestinal inflammatory diseases; however, its protective effects against neuronal inflammation are still undiscovered. Methods We investigated the anti-neuroinflammatory effects of HJT water extract on lipopolysaccharide (LPS)-stimulated BV2 mouse microglia cells. BV2 cells were treated with LPS (1 ㎍/mL) 1 hour prior to the addition of HJT. We measured cell viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and nitrite production using the Griess assay. We performed a reverse transcription-polymerase chain reaction assay to measure messenger RNA expression of inflammatory cytokines including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. Western blot analysis was performed to determine protein expression of mitogen-activated protein kinases (MAPKs) and inhibitor of nuclear factor kappa B (NF-κB)α. Results HJT inhibited excessive nitrite release in LPS-stimulated BV2 cells and also significantly inhibited inflammatory cytokines such as IL-1β, IL-6, and TNF-α in LPS-stimulated BV2 cells. Moreover, HJT significantly suppressed LPS-induced MAPK and NF-κB activation and inhibited the elevation of IL-1β, IL-6, and TNF-α in the brain of LPS-injected mice. Conclusions Our study highlights the anti-neuroinflammatory effects of HJT via MAPK and NF-κB deactivation.

Keywords

References

  1. Pan Y, Shen B, Gao Q, Zhu J, Dong J, Zhang L, Zhang Y. Caspase-1 inhibition attenuates activation of BV2 microglia induced by LPS-treated RAW264.7 macrophages. Journal of Biomedical Research. 2016;30(3):225-33.
  2. Trager U, Tabrizi SJ. Peripheral inflammation in neurodegeneration. J Mol Med. 2013;91(6):673-81. https://doi.org/10.1007/s00109-013-1026-0
  3. Whittemore ER, Loo DT, Cotman CW. Exposure to hydrogen peroxide induces cell death via apoptosis in cultured rat cortical neurons. Neuroreport. 1994;5(12):1485-8. https://doi.org/10.1097/00001756-199407000-00019
  4. Han Q, Yuan Q, Meng X, Huo J, Bao Y, Xie G. 6-shogaol attenuates LPS-induced inflammation in BV2 microglia cells by activating PPAR-γ. Oncotarget. 2017; 8(26):42001-6. https://doi.org/10.18632/oncotarget.16719
  5. Block ML, Zecca L, Hong JS. Microglia-mediated neurotoxicity: uncovering the molecular mechanism. Nat Rev Neurosci. 2007;8(1):57-69. https://doi.org/10.1038/nrn2038
  6. Perry VH, Nicoll JA, Holmes C. Microglia in neurodegenerative disease. Nat Rev Neurol. 2010;6(4):193-201. https://doi.org/10.1038/nrneurol.2010.17
  7. Yoon CS. Studies on the anti-neuroinflammatory effects of terpenes from Nardostachys jatamansi [dissertation]. Iksan:Wonkwang University; 2017.
  8. The Society of Korean Medicine Rehabilitation. Korean Medicine Rehabilitation. 4th rev. Seoul:Koonja Publishing. 2015:165-6.
  9. Association of Korean Medicine Professors for Cardiovascular and Neurological Medicine. Cardiovascular and neurological medicine in Korean medicine. Seoul: Koonja Publisher. 2013:428.
  10. The Korean Society of Oriental Neuropsychiatry. Korean medicine neuropasychiatry. Seoul:Jipmoondang Publisher. 2012:243-5, 332-4.
  11. Akshintala VS, Talukdar R, Singh VK, Goggins M. The gut microbiome in pancreatic disease. Clin Gastroenterol Hepatol. 2019;17(2):290-5. https://doi.org/10.1016/j.cgh.2018.08.045
  12. Zhang ZG. Gyeong-agjeonseo. Taipei:Daelyengookpyung Publisher. 1974:201.
  13. Heo J. Dongyibogam. Seoul:Bubin Publisher. 1999:450, 488, 576.
  14. Yun YG. Oriental herb medications and explanation, Seoul:Euiseongdang Publisher. 1998:62-3.
  15. Li Y, Liu TT, Li YT, Han DY, Hong JS, Yang N, He JD, Peng RH, Mi XN, Kuang CS, Zhou Y, Han YZ, Shi CM, Li ZQ, Guo XY. Baicalin ameliorates cognitive impairment and protects microglia from LPS-induced neuroinflammation via the SIRT1/HMGB1 pathway. Oxidative Medicine and Celluar Longevity. 2020;2020:4751349.
  16. Kim BW. Anti-inflammatory effect of Jakyakgamcho-tang. J Korean Oriental Internal Med. 2010;31(2):365-71.
  17. Kim E, Choi C, Kim I, Lee H, Song Y. Antibacterial effect of Huanggeumjakyak-tang against methicillin-resistant staphylococcus aureus. J Oriental Rehab Med. 2013;23(3):15-26.
  18. Kim MR, Kang OH, Kim SB, Kang HJ, Kim JE, Hwang HC, Kim IW, Kwon DY. The study of anti-inflammatory effect of Hwanggeumjakyak-tang extract in RAW 264.7 macrophage. Kor J Herbology. 2013;28(1):43-50. https://doi.org/10.6116/KJH.2013.28.1.43
  19. Thao D, Roger M, Susan V, Carl W. Lippincott's illustrated reviews: immunology. Seoul:Shinilbooks. 2008:179-82.
  20. Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology, 6/E. Seoul:Epublic. 2008: 28-31, 36-7, 210-1, 272-93.
  21. Heumjeongsagojeonseo. Huangjenaegyeongsomun Yeoungchu. Seoul:Daesung Publisher. 1995:369, 371.
  22. Zhang JB. LeiJing. Seoul:Bubin Publisher. 2006:1134-5.
  23. Kang HS, Park K. A study on the Hae Ron of the Young Chu. J Traditional Korean Medicine. 2000;10(1):83-97.
  24. Liu DZ. Chinese neurology, Tianjin:Tianjin Science and Technology Publisher. 1988:211-2.
  25. Shin MK. Clinical traditional herbalogy. Seoul:Yunglim Publisher. 2010:165, 237, 411.
  26. Han JH, Kiim KY. Herbal pharmacology. Seoul: Euiseongdang Publisher. 2009:137-44, 474-8, 493-5.
  27. Cho SH, Kim YR. Antimicrobial characteristics of scutellariae radix extract. J Korean Soc Food Sci Nutr. 2001;30(5):964-8.
  28. Lee JK, Song YK, Lim HH. Analgesic and anti-inflammatory effect of Scutellaria Baicalensis. J Korean Med. 2007;28(4):124-35.
  29. Sowndhararajan K, Deepa P, Kim MJ, Park SJ, Kim SM. Neuroprotective and cognitive enhancement potentials of Baicalin: a review. Brain Sciences. 2018;8(6):104. https://doi.org/10.3390/brainsci8060104
  30. Fang J, Zhu Y, Wang H, Cao B, Fei M, Niu W, Zhou Y, Wang X, Li X, Zhou M. Baicalin protects mice brain from apoptosis in traumatic brain injury model through activation of autophagy. Frontiers in Neuroscience. 2019;12:1006. https://doi.org/10.3389/fnins.2018.01006
  31. Bang MH, Song JC, Lee SY, Park NK, Baek NI. Isolation and structure determination of antioxidants from the root of Paeonia lactiflora. J Korean Soc Appl Bio Chem. 1999;42(2):170-5.
  32. Hong ND, Kim CW, Shin HD. A study on the analgesic and anti-convulsional effect of paeoniae radix. Korean J Pharmacogn. 1979;10(3):119-24.
  33. Han MH, Lee MH, Hong SH, Choi YH, Moon JS, Song MK, Kim MJ, Shin SJ, Hwang HJ. Comparison of anti-inflammatory activities among ethanol extracts of sophora flavescens, Glycyrrhiza uralensis and Dictamnus dasycarpus, and their mixtures in RAW 246.7 murine macrophages. Journal of Life Science. 2014;24(3):329-35. https://doi.org/10.5352/JLS.2014.24.3.329
  34. Lim NR. Effects of Boehmeria nivea on antioxidant, the regulation of neuro-protection and neuro-inflammation [dissertation]. Iksan:Wonkwang University; 2020.
  35. Yoon CS, Kim DC, Ko WM, Kim KS, Lee DS, Kim DS, Cho HK, Seo JW, Kim SY, Oh HC, Kim YC. Anti-neuroinflammatory effects of Quercetin-3-O-glucuronide isolated from the leaf of Vitis labruscana on LPS-induced neuroinflammation in BV2 cells. Kor J Pharmacogn. 2014;45(1):17-22.
  36. Kim DC. Neuroprotective and anti-neuroinflammatory effects of 4-methoxydalbergione and 4'-hydroxy-4-methoxydalbergione from Dalbergia odorifera in mouse hippocampal and microglial cells [dissertation]. Iksan: Wonkwang University; 2015.
  37. Jin HG, Kim KW, Li J, Im HR, Lee DY, Yoon DH, Jeong JT, Kim GS, Oh HC, An RB, Kim YC. Atractylenoide II isolated from atractylodes macrocephala inhibited inflammatory responses in lipopolysaccharide-induced RAW264.7 macrophages and BV2 microglia cells. Kor J Pharmacogn. 2020;51(4):244-54. https://doi.org/10.22889/KJP.2020.51.4.244