Herbal Formula Science (대한한의학방제학회지)

The Korean Medicine Society for the Herbal Formula Study (대한한의학방제학회)
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Anti-inflammatory and Antioxidant Effects of Cheongnoimyungshin-hwan in RAW 264.7 Macrophages

RAW 264.7 대식세포에서 청뇌명신환(淸腦明神丸)에 의한 염증성 및 산화적 스트레스 반응 억제 효능

  • Son, Byun Woo (Department of Korean Internal Medicine, College Of Korean Medicine, Dong-Eui University) ;
  • Lee, Myeong Hwa (Department of Korean Internal Medicine, College Of Korean Medicine, Dong-Eui University) ;
  • Hwang, Won Deok (Department of Korean Internal Medicine, College Of Korean Medicine, Dong-Eui University)
  • 손변우 (동의대학교 한의과대학 내과학교실) ;
  • 이명화 (동의대학교 한의과대학 내과학교실) ;
  • 황원덕 (동의대학교 한의과대학 내과학교실)
  • Received : 2018.01.12
  • Accepted : 2018.01.25
  • Published : 2018.02.28
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Abstract

Objectives : Cheongnoimyungshin-hwan (CNMSH) is a Herbal compound prescription that is composed mainly of herbal medicines such as Ginseng Radix Alba, Angelicae Gigantis Radix, Dioscoreae Rhizoma, Longan Arillus and cornus cervi parvum, and for the purpose of improving memory and preventing dementia. Methods : In this study, it was investigated whether CNMSH could suppress inflammatory response and oxidative stress in the lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. As a result, CNMSH decreased expression of inducible nitric oxide (NO) synthase and cyclooxygenase-2, and also inhibited production of NO, prostaglandin E2. Results : This effect was associated with the suppression of the expression of p65, one of the nuclear factor-kappaB ($NF-{\kappa}B$) subunits, and increased expression of $I{\kappa}B-{\alpha}$, inhibit the $NF-{\kappa}B$ transcription factor. In addition, CNMSH significantly blocked intracellular reactive oxygen species accumulation in response to LPS stimulation. Furthermore, CNMSH increased expression of nuclear factor erythroid 2-related factor (Nrf)-2 activation and heme oxygenase (HO)-1. Conclusions : Therefore, it has been shown anti-inflammatory and antioxidant effects by inhibiting the expression and production of inflammatory mediators in LPS-stimulated macrophages, and is associated with ROS generation and is activated by Nrf2/HO-1 signaling pathway.

Keywords

References

  1. Lee SH, Jung BH, Kim SY, Chung BC. Determination of phytoestrogens in traditional medicinal herbs using gas chromatography-mass spectrometry. J Nutr Biochem. 2004; 15: 452-460. https://doi.org/10.1016/j.jnutbio.2004.01.007
  2. Wasser SP, Weis AL. Therapeutic effects of substances occurring in higher basidiomycetes mushrooms: a modern perspective. Crit Rev Immunol. 1999; 19: 65-96.
  3. Heo J. The Dongui Bogam. Yeo-Gang Publisher. 2001:1750
  4. Pi GH, and Hwang WD. Neuroprotective effects of Cheongnoemyeongsin-hwan against hydrogen peroxide-induced DNA damage and apoptosis in human neuronal-derived SH-SY5Y cells. Herbal Formula Science. 2017; 25(1): 51-68. https://doi.org/10.14374/HFS.2017.25.1.51
  5. Im YG, Choi YH, Hwang WD. Anti-inflammatory Effects of Cheongnoimyungshin-hwan in Microglia Cells. The Korean Society of Oriental Neuropsychiatry. 2014; 25(4): 423-433. https://doi.org/10.7231/jon.2014.25.4.423
  6. Chang SH, Hwang WD. Ameliorating Effects of Cheongnoemyeongsin-hwan on Learning and Memory Impairment Induced by Cerebral Hypoperfusion in Rats The Korean Medicine Society for The Herbal Formula Study 2017;25(1): 69-87. https://doi.org/10.14374/HFS.2017.25.1.69
  7. Lee DH, Park JS, Lee YS, Sung SH, Lee YH, and Bae SH. The hypertension drug, verapamil, activates Nrf2 by promoting p62-dependent autophagic Keap1 degradation and prevents acetaminophen-induced cytotoxicity. BMB Rep. 2017; 50: 91-96. https://doi.org/10.5483/BMBRep.2017.50.2.188
  8. Kong YH, Lee YC, Choi SY. Neuroprotective and Anti-inflammatory effects of phenolic compounds in Panax ginseng C.A. Meyer. J Ginseng Res. 2009; 33: 111-114. https://doi.org/10.5142/JGR.2009.33.2.111
  9. Jang SI, Kim HJ, Hwang KM, Pae HO, Yun YG, Chung HT, Kim YC. Anti-Inflammatory Effect of Ethanol Extract of Angelica uchiyamana in Activated Murine RAW 264.7 macrophages. Korean J Oriental Medical Prescription. 2002; 10: 189-197.
  10. Choi GY, Kim BW. Experimental study on the antioxidant and antimicrobial properties of Dioscoreae Rhizoma. Korean J Orient Int Med, 2010; 31: 290-297.
  11. Kim MR, Lim EM. Effects of Longanae arillus water extract on inflammatory response and cytokines in mouse macrophage cells. J Korean Obstet Gynecol. 2014; 27: 1-11.
  12. Willoughby DA, Heberden O. Human arthritis applied to animal models. Towards a better therapy. Ann Rheum Dis. 1975; 34: 471-478. https://doi.org/10.1136/ard.34.6.471
  13. Sirisinha S. Insight into the mechanisms regulating immune homeostasis in health and disease. Asian Pac J Allergy Immunol. 2001; 29: 1-14.
  14. Kook YB. Effect of Hwangryunhaedok-tang on blood pressure and renal functions in spontaneously hypertensive rats. The Korean Journal of Oriental Medical Prescription. 2002; 10: 113-129.
  15. Mann JR, Backlund MG, DuBois RN. Mechanism of disease: Inflammatory mediators and cancer prevention. Nat Clin Pract Oncol. 2005; 2: 202-210.
  16. Cho BO, Ryu HW, So Y, Lee CW, Jin CH, Yook HS, et al. Anti-inflammatory effect of mangostenone F in lipopolysaccharide-stimulated RAW 264.7 macrophages by suppressing $NF-{\kappa}B$ and MAPK activation. Biomol Ther. 2014; 22: 288-294. https://doi.org/10.4062/biomolther.2014.052
  17. Higuchi M, Hisgahi N, Taki H, Osawa T. Cytolytic mechanisms of activated macrophages. Tumor necrosis factor and L-arginine-dependent mechanisms act synergistically as the major cytolytic mechanisms of activated macrophages. J Immunol. 1990; 144: 1425-1431.
  18. Jin KS, Park JY, Cho MK, Jang JH, Jeong JH., Ok S, Bak MJ, Song YS, Kim MJ, Cho CW, Jeong WS. Modulation of Nrf2/ARE and inflammatory signaling pathways by Hericium erinaceus mycelia extract. Food Sci Biotechnol. 2009; 18: 1204-1211.
  19. Park CM, Jing KS, Lee YW, Song YS. Luteolin and chicoric acid synergistically inhibited inflammatory responses via inactivation of PI3K-Akt pathway and impairment of $NF-{\kappa}B$ translocation in LPS stimulated RAW 264.7 cells. Eur J Pharmacol. 2011; 660: 454-459. https://doi.org/10.1016/j.ejphar.2011.04.007
  20. Karin M, Ben-Neriah Y. Phosphorylation meets ubiquitination: The control of $NF-{\kappa}B$ activity. Annu Rev Immunol. 2000; 18: 621-663. https://doi.org/10.1146/annurev.immunol.18.1.621
  21. Elewaut D, DiDonato JA, Kim JM, Truong F, regulator of the intestinal epithelial cell innate immune response induced by infection with enteroinvasive bacteria. J Immunol. 1999; 163: 1457-1466.
  22. Halliwell B. Antioxidants in human health and disease. Annu Rev Nutr. 1996; 16: 33-50. https://doi.org/10.1146/annurev.nu.16.070196.000341
  23. McCord JM, Wong K, Stokes SH, Petrone WF, English D. Superoxide and inflammation: a mechanism for the anti-inflammatory activity of superoxide dismutase. Acta Physiol Scand Suppl. 1980; 492: 25-30.
  24. Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB. Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal. 2014; 20: 1126-1167. https://doi.org/10.1089/ars.2012.5149
  25. Kasahara E, Sekiyama A, Hori M, Hara K, Takahashi N, Konishi M, et al. Mitochondrial density contributes to the immune response of macrophages to lipopolysaccharide via the MAPK pathway. FEBS Lett. 2011; 585: 2263-2268. https://doi.org/10.1016/j.febslet.2011.05.049
  26. Maines MD. The heme oxygenase system : a regulator of second messenger gases. Annu Rev Pharmacol Toxicol. 1997; 37: 517-554. https://doi.org/10.1146/annurev.pharmtox.37.1.517
  27. Lee TS, Chau LY. Heme oxygenase-1 mediates the anti-inflammatory effecy of interleukin-10 in mice. Nat Med. 2002; 8: 240-246. https://doi.org/10.1038/nm0302-240
  28. Nakao A, Otterbein LE, Overhaus M, Sarady JK, Tsung A, Kimizuka K, et al. Bilicerdin protects the functional integrity of a transplanted syngeneic small bowel. Gastroenterology. 2004; 127: 595-606. https://doi.org/10.1053/j.gastro.2004.05.059
  29. Huang BP, Lin CH, Chen HM, Lin JT, Cheng YF, Kao SH. AMPK activation inhibits expression of proinflammatory mediators through downregulation of PI3K/p38 MAPK and $NF-{\kappa}B$ signaling in murine macrophages. DNA Cell Biol. 2015; 34: 133-141. https://doi.org/10.1089/dna.2014.2630
  30. Huang Y, Li W, Su ZY, Kong AN. The complexity of the Nrf2 pathway: beyond the antioxidant response. J Nutr Biochem. 2015; 26: 1401-1413. https://doi.org/10.1016/j.jnutbio.2015.08.001
  31. Kang KA, Hyun JW. Oxidative stress, Nrf2, and epigenetic modification contribute to anticancer drug resistance. Toxicol Res. 2017; 33: 1-5. https://doi.org/10.5487/TR.2017.33.1.001