The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology (한방안이비인후피부과학회지)

The Society of Korean Medicine Ophthalmology, Otolaryngology & Dermatology (대한한방안이비인후피부과학회)
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Anti-inflammatory Effects of Tanghwajitong-san through Inhibition of NF-κB and MAPK

탕화지통산(湯火止痛散)의 NF-κB 및 MAPK 억제를 통한 항염증 효과

  • Min Jung, Ko (Woobo Korean Medical Clinic Changwon Branch) ;
  • Seon Young, Jee (Dep. of Korean Medicine Ophthalmology & Otolaryngology & Dermatology, Daegu Hanny University) ;
  • Min, Hwangbo (Dep. of Korean Medicine Ophthalmology & Otolaryngology & Dermatology, Daegu Hanny University)
  • 고민정 (우보한의원 창원점) ;
  • 지선영 (대구한의대학교 한의과대학 안이비인후피부과학교실) ;
  • 황보민 (대구한의대학교 한의과대학 안이비인후피부과학교실)
  • Received : 2023.01.16
  • Accepted : 2023.02.07
  • Published : 2023.02.25
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Abstract

Objectives : The purpose of this study was to evaluate the anti-inflammatory effect of Tanghwajitongsan(THJTS) through inhibition of NF-κB and MAPK. Methods : We evaluated cell survival rate by MTT assay, NO production by nitrite content in the culture medium. We quantified TNF-α, IL-1β, IL-6 and PGE2 of the cultured supernatant by ELISA. And we evaluated the effect of THJTS on protein expression of NF-κB, MAPK, iNOS and COX-2 by Western blot analysis. THJTS ameliorates LPS-activated alterations in protein expression of NF-κB, p-38, iNOS and COX-2 and production of NO, pro-inflammatory cytokines and PGE2. Also, THJTS ameliorates LOX, PGN and FLA-activated alterations in protein expression of NO, iNOS. THJTS ameliorates only PGN-activated alterations in protein expression of COX-2. Results : THJTS ameliorates LPS-activated alterations in protein expression of NF-κB, p-38, iNOS and COX-2 and production of NO, pro-inflammatory cytokines and PGE2. Also, THJTS ameliorates LOX, PGN and FLA-activated alterations in protein expression of NO, iNOS. THJTS ameliorates only PGN-activated alterations in protein expression of COX-2. Conclusions : This study can provide scientific evidence for the anti-inflammatory effects and underlying mechanisms of THJTS.

Keywords

References

  1. Jo SJ, Seo HS, Jee SY, Hwangbo M, Kim CY, Kwon K. Efficacy of Herbal Medicines for the Treatment Burns : A Systematic Review and Meta-analysis. J Korean Med Ophthalmol Otolaryngol Dermatol. 2021;34(4):90-116.
  2. Kang WH. Diseases of Skin Atlas. Seoul:Hanmiuihak. 2006:61.
  3. The Korean Society of Pathology. Pathology. Seoul:Komoosa. 1995:71-104.
  4. Yu MK, Jeong DH, Sim SH, Park SY, Choi JH, Kim JH. A Literature Study on the External Treatment of a Burn. J Korean Med Ophthalmol Otolaryngol Dermatol. 2003;16(3):38-67.
  5. Jeon DH. Silyoung Junguidaeyakgang. Beijing:People's Medical Publshing House Co. 2000:774.
  6. Lee SA, Kong R, Kang OH, Seo YS, Zhou T, Kim SA, et al. The antimicrobial activity of Daehwanggo against Methicillin-resistant Staphylococcus aureus. Kor J Herbology. 2017;32(2):87-95. https://doi.org/10.6116/KJH.2017.32.2.87
  7. Jeon DJ, Cha YY, Lee E. Inflammatory Effect of Rheum undulatum L. J Oriental Rehab Med. 2011;21(1):35-46.
  8. Park SM, Lee KW, Jo YH. Effect of Rheum undulatum Extract on Antioxidant Activity and Activity of Matrix Metalloproteinase-1 in Human Skin Fibroblasts. Journal of Life Science. 2008;18(12):1700-4. https://doi.org/10.5352/JLS.2008.18.12.1700
  9. Yun HJ, Hwang SG, Yun HJ, Kim CH, Seo GS, Park WH, et al. Original Articles : Anticancer effect of Rheum Rhizoma on human Liver cancer HepG2 cells. Kor J Herbology. 2006;21(4):27-36.
  10. Jang SI, Kim JH, Hwang KM, Pae HO, Yun YG, Chung HT, et al. Anti-Inflammatory Effect of Ethanol Extract of Angelica uchiyamana in Activated Murine RAW 264.7 macrophages. The Korean Journal of medical Prescription. 2002;10(2):189-97.
  11. Park H, Jung CR, Eom AH. Species Diversity and Antifungal Activity of Endophytic Fungi Isolated from Angelica gigas Nakai. The Korean Journal of Mycology. 2021;49(4):497-505. https://doi.org/10.4489/KJM.20210048
  12. Kim MY, Kwon OJ, Choo BK, Lee CW, Park EH, Kim HJ. The Effect of Angelicae gigantis radix according to Heat-process on Anti-Oxidant and Anti-Thrombotic. Kor J Herbology. 2015;31(3):13-22. https://doi.org/10.6116/kjh.2016.31.3.13.
  13. Park KW, Choi SR, Shon MY, Jeong IY, Kang KS, Lee ST, et al. Cytotoxic Effects of Decursin from Angelica gigas Nakai in Human Cancer Cells. J Korean Soc Food Sci Nutr. 2007;36(11):1385-90. https://doi.org/10.3746/jkfn.2007.36.11.1385
  14. Jeong HJ, Hong SY, Lee KY, Lee JH, Lim SH, Heo NK, et al. Diabetic Effect Of Angelica gigas Nakai Leaf Extracts in Diabetes Mellitus Type II Model Mice by High Fat-fed and Streptozotocin-treated Rats. Journal of Agricultura, Life and Environmental Sciences. 2015;27(1):6-14.
  15. Kim IR, Kim HC, Kuk YB, Park SJ, Park YG, Park JH, et al. Bonchohak. 3rd ed. Seoul: Younglimsa. 1992;285,286,632,633.
  16. Cho YH. Concepts of Human Physiology. Seoul:Bummoon Education. 2011:202.
  17. Tacke F. Targeting hepatic macrophages to treat liver diseases. J Hepatol. 2017;66:1300-12. https://doi.org/10.1016/j.jhep.2017.02.026
  18. Abbas AK, Lichtman AH, Phillai S. Cellular and molecular immunology. 7th ed. Philadelphia:Saunders. 2012:41-88.
  19. Kuzmich NN, Sivak KV, Chubarev VN, Porozov YB, Savateeva-Lyubimova TN, Peri F. TLR4 signaling pathway modulators as potential therapeutics in inflammation and sepsis. Vaccines. 2017;5:34.
  20. Abbas AK, Andrew H. Lichman. Cellular and Molecular Immunology. 5th ed. Philadelpia: Saunders. 2003:25,282-8,493,507.
  21. Lee SI. Cheonjincheobangheaseol. Seoul: Younglimsa. 1995:23.
  22. Seo WG, Pae HO, Oh GS, Kim NY, Kwon TO, Shin MK, et al. The aqueous extract of Rhodiola sachalinensis root enhances the expression of inducible nitric oxide synthase gene in RAW264.7 macrophages. J Ethnopharmacol. 2001;76:119-23. https://doi.org/10.1016/S0378-8741(01)00220-3
  23. Chiou WF, Chou CJ, Chen CF. Camptothecin suppresses nitric oxide biosynthesis in RAW 264.7 macrophages. Life Sci. 2001;69:625-35. https://doi.org/10.1016/S0024-3205(01)01154-7
  24. Kawamata H, Ochiai H, Mantani N, Terasawa K. Enhanced expression of inducible nitric oxide synthase by Juzen-taiho-to in LPS-activated RAW 264.7 cells, a murine macrophage cell line. Am J Chin Med. 2000;28:217-26. https://doi.org/10.1142/S0192415X0000026X
  25. Paige JS, Jaffrey SR. Pharmacologic manipulation of nitric oxide signaling: targeting NOS dimerization and protein-protein interactions. Curr Top Med Chem. 2007;7(1):97-114. https://doi.org/10.2174/156802607779318253
  26. Palmer RM, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature. 1988;333:664-6. https://doi.org/10.1038/333664a0
  27. Takeda K, Akira S. Toll-like receptors in innate immunity. Int Immunol. 2005;17:1-14. https://doi.org/10.1093/intimm/dxh186
  28. Medzhilov R. Toll-like receptors and innate immunity. Nat Rev Immunol. 2001;1:135-45. https://doi.org/10.1038/35100529
  29. O'Neill LA. TLRs: Professor Mechnikov, sit on your hat. Trends Immunol. 2004;25:687-93. https://doi.org/10.1016/j.it.2004.10.005
  30. Vogel SN, Fitzgerald KA, Fenton MJ. TLRs: differential adapter utilization by toll-like receptors mediates TLR-specific patterns of gene expression. Mol Interv. 2003;3:466-77. https://doi.org/10.1124/mi.3.8.466
  31. Medzhitov R. Toll-like receptors and innate immunity. Nat Rev Immunol. 2001;1:135-45. https://doi.org/10.1038/35100529
  32. Wright SD, Tobias PS, Ulevitch RJ, Ramos RA. Lipopolysaccharide(LPS) binding protein opsonizes LPS-bearing particles for recognition by a novel receptor on macrophages. J Exp Med. 1989;170:1231-41. https://doi.org/10.1084/jem.170.4.1231
  33. Wright SD, Ramos RA, Tobias PS, Ulevitch RJ, Mathison JC. CD14, a receptor for complexes of lipopolysaccharide(LPS) and LPS binding protein. Science. 1990;249:1431-3. https://doi.org/10.1126/science.1698311
  34. Hayashi F, Smith KD, Ozinsky A, Hawn TR, Yi EC, Goodlett DR, et al. The innate immune response to bacterial flagellin is mediated by Toll-like receptor-5. Nature. 2001;410:1099-103. https://doi.org/10.1038/35074106
  35. Hemmi H, Kaisho T, Takeuchi O, Sato S, Sanjo S, Hoshino K, et al. Small antiviral compounds activate immune cells via TLR7 MyD88-dependent signaling pathway. Nat Immunol. 2002;3:196-200.
  36. Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med. 1993;329(27):2002-12. https://doi.org/10.1056/NEJM199312303292706
  37. Assumpcao CR, Brunini TMC, Matsuura C, Resende AC, Mendes-Ribeiro AC. Impact of the L-arginine-Nitric Oxide Pathway and Oxidative Stress on the Pathogenesis of the Metabolic Syndrome. Open Biochem J. 2008;2:108-15. https://doi.org/10.2174/1874091X00802010108
  38. Parham P. Immune System. 4th ed. Seoul: Lifescience Publishing. 2016:31-85.
  39. Coico R, Sunshine G. Immunology A Short Course. 6th ed. Seoul:Worldscience. 2012:11-9,167-72.
  40. Simmons DL, Botting RM, Hla T. Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacol Rev. 2004;56(3):387-437. https://doi.org/10.1124/pr.56.3.3
  41. Cario E. Barrier-protective function of intestinal epithelial Toll-like receptor 2. Mucosal Immunology. 2008;1:S61-6. https://doi.org/10.1038/mi.2008.47
  42. Delgado AV, McManus AT, Chambers JP. Production of tumor necrosis factor-alpha, interleukin 1-beta, interleukin 2, and interleukin 6 by rat leukocyte subpopulations after exposure to substance P. Neuropeptides. 2003;37(6):355-61. https://doi.org/10.1016/j.npep.2003.09.005
  43. Gulhar R, Ashraf MA, Jialal I. Physiology, Acute Phase Reactants. 2020[updated 2020 MAY 4]. Available from: URL:https://www.ncbi.nlm.nih.gov/books/NBK519570/
  44. Chen F, Castranova V, Shi X. New insights into the role of nuclear factor-kappaB in cell growth regulation. Am J Pathol. 2001;159(2):387-97. https://doi.org/10.1016/S0002-9440(10)61708-7
  45. Alam MB, Ju MK, Kwon YG, Lee SH. Protopine attenuates inflammation stimulated by carrageenan and LPS via the MAPK/NF-kappaB pathway. Food Chem Toxicol. 2019;131:110583.
  46. Wang H, Huang W, Liang M, Shi Y, Zhang C, Li Q, et al. (+)-JQ1 attenuated LPS-induced microglial inflammation via MAPK/NFκB signaling. Cell Biosci. 2018;8:60.
  47. Kim MK, Kim DY. Anti-inflammatory Effect of an Ecklonia cava Ethanol Extract in Macrophage via Inhibition of the NF-κB/MAPK Signal Pathways. J Chitin Chitosan. 2016;21(4):236-41. https://doi.org/10.17642/jcc.21.4.2
  48. Shen J, Sakaida I, Uchida K, Terai S, Okita K. Leptin enhances TNF-alpha production via p38 and JNK MAPK in LPS-stimulated Kupffer cells. Life Sci. 2005;77(13):1502-15. https://doi.org/10.1016/j.lfs.2005.04.004
  49. Park HY, Han MH, Park C, Jin CY, Kim GY, Choi IW, et al. Anti-inflammatory effects of fucoidan through inhibition of NF-κB, MAPK and Akt activation in lipopolysaccharideinduced BV2 microglia cells. Food and Chemical Toxicology. 2011;49:1745-52. https://doi.org/10.1016/j.fct.2011.04.020
  50. Rao CV, Verma AR, Gupta PK, Vijayakumar M. Anti-inflammatory and anti-nociceptive activities of Fumaria indica whole plant extract in experimental animals. Acta Pharm. 2007;57:491-8. https://doi.org/10.2478/v10007-007-0039-z
  51. Lee JH, Choi YH, Choi BT. The anti-inflam matory effects of 2 Hz electroacupuncture w ith different intensities on acute carrageena n-induced inflammation in the rat paw. Int J Mol Med. 2005;16:99-102.