The Journal of Internal Korean Medicine (대한한방내과학회지)

The Society of Internal Korean Medicine (대한한방내과학회)
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Inhibitory Effects of Dansam and Dansam-eum on Reflux Esophagitis and Migration of Cancer Cells

단삼과 단삼음의 역류성 식도염 억제 효과 및 암세포 이주 억제 효과

  • Jung-yeon, Kwon (Dept. of Korean Internal Medicine, College of Korean Medicine, Se-Myung University) ;
  • Sang-hyun, An (Dept. of Anatomy, College of Korean Medicine, Se-Myung University) ;
  • Kyung-hwan, Kong (Dept. of Korean Internal Medicine, College of Korean Medicine, Se-Myung University)
  • 권정연 (세명대학교 한의과대학 한방내과학교실) ;
  • 안상현 (세명대학교 한의과대학 해부학교실) ;
  • 공경환 (세명대학교 한의과대학 한방내과학교실)
  • Received : 2022.12.04
  • Accepted : 2022.12.22
  • Published : 2022.12.30
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Abstract

Purpose: We examined the effects of Dansam (Salvia miltiorrhiza Bunge, SM) and Dansam-eum (DSE) on gastroesophageal reflux disease (GERD) and reflux esophagitis by comparing the inhibitory effects of SM and DSE with the representative treatment of PPI Omeprazole to determine if the effects of the prescription DSE based on Korean medicine are better than those of a single-use of SM. Methods: We performed experiments using both animal models and cancer cells. Results: Comparison of SM and DSE with PPI in the animal model tests revealed that the effects were superior for SM and DSE than for PPI in all categories (8-OHdG, p-IκB, PAR2, COX-1, cathelicidin, p-JNK, Caspase 3, ATP6V1B1, GRPR, serotonin, and NPY). In three categories (COX-1, serotonin, and NPY), SM and DSE showed superior results over the Controls. In the animal model tests, DSE was superior to SM in all categories except for serotonin. The anti-cancer effects observed in cancer cell tests revealed that SM and DSE had meaningful results in terms of cytotoxicity and cell movement rate, as well as in cancer cell apoptosis. Conclusions: We confirmed that SM and DSE can have effects on reflux esophagitis through the regulation of oxidative stress, inflammation, mucosal protection, apoptosis, proton pumping, and the enteroendocrine system in the stomach and esophagus. We also confirmed that SM and DSE have superior effects to those of PPI on all aspects, especially gastric mucosa protection and enteroendocrine system control. We also confirmed that SM and DSE have anti-cancer effects. Above all, we confirmed that DSE has superior effects on almost all aspects compared to using SM alone.

Keywords

References

  1. Jung HK, Hong SJ, Jo YJ, Jeon SW, Cho YK, Lee KJ, et al. Updated Guidelines 2012 for Gastroesophageal Reflux Disease. Korean J Gastroenterol 2012;60(4):195-218. https://doi.org/10.4166/kjg.2012.60.4.195
  2. Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, et al. Harrison's Principles of Internal Medicine 17th edition. Seoul: MIP; 2010, p. 688-92, 2232-4.
  3. Maton PN. Omeprazole. N Engl J Med 1991; 324(14):965-75. https://doi.org/10.1056/NEJM199104043241406
  4. Kim DH, Lee JE, You SH, Lee HA, Park JH, Jung JH, et al. Proton pump inhibitor use and risk of osteoporotic fracture in Korean adults with peptic ulcer disease and gastroesophageal reflux disease Seoul: National Evidence-based Healthcare Collaborating Agency; 2017, p. 67-70.
  5. Cheungpasitporn W, Thongprayoon C, Kittanamongkolchai W, Srivali N, Edmonds PJ, Ungprasert P, et al. Proton pump inhibitors linked to hypomagnesemia: a systematic review and meta-analysis of observational studies. Ren Fail 2015;37(7):1237-41. https://doi.org/10.3109/0886022X.2015.1057800
  6. Park HJ, Park SH, Shim KN, Kim YS, Kim HY, Han JP, et al. The Prevalence and Clinical Features of Non-responsive Gastroesophageal Reflux Disease to Practical Proton Pump Inhibitor Dose in Korea: A Multicenter Study. Korean J Gastroenterol 2016;68(1):16-22. https://doi.org/10.4166/kjg.2016.68.1.16
  7. Makunts T, Alpatty S, Lee KC, Atayee RS, Abagyan R. Atayee & Ruben Abagyan. Proton-pump inhibitor use is associated with a broad spectrum of neurological adverse events including impaired hearing, vision, and memory. Scientific Reports 2019;9(1):17280.
  8. Bezabeh S, Mackey AC, Kluetz P, Jappar D, Korvick J. Accumulating Evidence for a Drug-Drug Interaction Between Methotrexate and Proton Pump Inhibitors. The Oncologist 2012;17(4):550-4. https://doi.org/10.1634/theoncologist.2011-0431
  9. 黃度淵. 新增 方藥合編. 서울: 永林社; 2010, p. 391.
  10. 陳修園. 醫學全書⋅時方歌括. 北京: 中國中醫藥 出版社; 2006, p. 956.
  11. 전국한의과대학 본초학 교수 공편저. 본초학. Seoul: 永林社; 2011, p. 336-7, 404-5, 458-9.
  12. Jeon CM, Min GW, Park JH, Yoon CH, Jeong JC, Kang JJ, et al. Effect of the methanol extract of Dansameum on the ammonia-induced peptic ulcer in rats. Korean J Orient Int Med 2000;21(4):597-604.
  13. Lee SE, Cho SI. Anti-inflammatory effects of Salviae Miltiorrhizae Radix extract on RAW264.7 cell. via anti-oxidative activities. Kor J Herbol 2015;30(4):89-94.
  14. Shon YH, Cho HJ, Hyeun WC, Son KH, Nam KS. Chemopreventive Potential of Salvia miltiorrhiza Fraction Extracts. Journal of Life Science 2006; 16(3):369-74. https://doi.org/10.5352/JLS.2006.16.3.369
  15. Choi SM, Choi SH, Ahn KS. Study on Antitumor and Apoptosis - Inducing Effects of Salviae miltiorrhizae Radix. Korean J of Oriental Medical Pathology 2000;14(2):22-47.
  16. Lee WYW, Cheung CCM, Liu KWK, Fung KP, Wong J, Lai PBS, et al. Cytotoxic effects of tanshinones from Salvia miltiorrhiza on doxorubicin-resistant human liver cancer cells. J Nat Prod 2010;73(5):854-9.
  17. Cha JY, Ha SE, Sim SM, Park JK, Chung YO, Kim HJ, et al. Antimicrobial Effects of Ethanol Extracts of Korea Endemic Herb Plants. Journal of Life Science 2008;18(2):228-33. https://doi.org/10.5352/JLS.2008.18.2.228
  18. Lee SK, Lim SW. The Administration of Jeungmiyijin-tang to Rats with Induced Gastro Reflux Esophagitis. J Int Korean Med 2016;37(6):1030-41. https://doi.org/10.22246/jikm.2016.37.6.1030
  19. Lee ST, Kwak MA. Effects of Individual Herbal Components of Yijintang-gamibang in the Rat Reflux Esophagitis. Korean J Orient Int Med 2013;34(2):165-77.
  20. Jang MW, Lim SW. Experimental Study for Effect of Banhasasim-tang on Mice with Reflux Esophagitis. Korean J Orient Int Med 2013;34(4):362-3.
  21. Shin MK, Kim ES, Kim TR, Lim HC, Lee YS. Effects of Jwa Kum-Whan on Reflux Esophagitis in Rats. J Int Korean Med 2016;37(3):495-507.
  22. Lee JA, Park HJ, Kim SH, Kim MJ, Kim KJ, Shin MR, et al. Evaluation of Evodiae Fructus Extract on the Chronic Acid Reflux Esophagitis in Rats. Kor J Herbol 2019;34(2):15-23. https://doi.org/10.6116/KJH.2019.34.2.15
  23. Kim DJ, Roh SS. Effect on Acute reflux Esophagitis by Evodiae Fructus Aquous Extract. Kor J Herbol 2012;27(1):51-8. https://doi.org/10.6116/KJH.2012.27.1.51
  24. Kim SH, Roh SS, Lee JA, Shin MR, Lee AR, Koo JS, et al. Improving Effects on Rats with Chronic Acid Reflux Esophagitis Treated of Coptidis Rhizoma Extract. Kor J Herbol 2019;34(1):117-24. https://doi.org/10.6116/KJH.2019.34.1.117
  25. Lee JY, Seo BI, Roh SS. Improving effect of Artemisiae Capillaris Herba extract in reflux esophagitis rats. Kor J Herbol 2016;31(6):37-44. https://doi.org/10.6116/KJH.2016.31.6.37.
  26. Kwon OJ, Lee AR, Roh SS. Improving Effects on Rats with Reflux Esophagitis Treated with Combined Extract of Young persimmon fruit and Citrus peel. Kor J Herbol 2016;31(1):25-31. https://doi.org/10.6116/KJH.2016.31.1.25.
  27. Kim MY, Shin YO, Lee JY, Lee AR, Shin SH, Kwon OJ, et al. Improving Effect of a Combined Extract of Rhei Rhizoma and Glycyrrhizae Rhizoma through Anti-oxidative Stress in Reflux Esophagitis rats. Kor J Herbol 2015;30(4):37-44. https://doi.org/10.6116/KJH.2015.30.4.37.
  28. Shin MR, Lee JA, Kim MJ, An HJ, Roh SS. The protective effect of Areca Semen and Toosendan Fructus mixture in a chronic model of reflux esophagitis. Kor J Herbol 2020;35(1):57-68. https://doi.org/10.6116/KJH.2020.35.1.57
  29. Song CH, Baek TH. A Comparative Study of Sepiae Os, Arcae Concha, Ostreae Concha and Esomeprazole in a Mouse Model of Reflux Esophagitis. J Korean Med 2018;39(2):92-105. https://doi.org/10.13048/jkm.18018
  30. Shin MH, Kim ES, Lee YS. Suppressive Effects of Ulmi Pumilae Cortex Extracts on the Reflux Esophagitis in Rat. J Physiol & Pathol Korean Med 2016;30(4):257-65. https://doi.org/10.15188/kjopp.2016.08.30.4.257
  31. Choi MJ, Yang WJ, Lee BH, Cho SI. Basic network pharmacological analysis of Salvia miltiorrhiza root for further application to an animal stroke model. Herbal Formula Science 2021;29(1):19-31.
  32. Kim BC, Lee EJ, Park CS, Park CG. The Experimental Study on the Effects of Dansamyeum on Hyperlipidemia. Kor J Orient Int Med 2000;21(1):126-34.
  33. Son CS, Kwon KB, Kim SB, Lee HS, Seo EH, Lee HS, et al. Effects of Dansamyeum Water Extract on Heart Beating Rate in Cultured Mouse Myocardial Cells. Korean J Oriental Medical Physiology & Pathology 2001;15(2):241-5.
  34. Jeon CM, Min GU, Park JH, Yoon CH, Jeong JC, Kang JJ, et al. Effect of the methanol extract of Dansameum on the ammonia-induced peptic ulcer in rats. Kor J Orient Int Med 2000;21(4):597-604.
  35. Shapiro M, Green C, Bautista JM, Dekel R, Risner-Adler S, Whitacre R, et al. Assessment of dietary nutrients that influence perception of intraoesophageal acid reflux events in patients with gastro-esophageal reflux disease. Aliment Pharmacol Ther 2007;25(1):93-101.
  36. Nakamura k, Ozawa Y, Furuta Y, Omd Miyazaki H. Effects of sodiumpolyacrylate (PANa) on acute esophagitis by gastric juice in rats. Japan J Pharmacol 1982;32(3):445-56. https://doi.org/10.1016/S0021-5198(19)52665-8
  37. Zhou X, Zhuang Z, Wang W, He L, Wu H, Cao Y, et al. OGG1 is essential in oxidative stress induced DNA demethylation. Cell Signal 2016;28(9):1163-71. https://doi.org/10.1016/j.cellsig.2016.05.021
  38. Valavanidis A, Vlachogianni T, Fiotakis C. 8-hydroxy-2'-deoxyguanosine (8-OHdG):A critical biomarker of oxidative stress and carcinogenesis. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 2009;27(2):120-39. https://doi.org/10.1080/10590500902885684
  39. Lazzerini PE, Lorenzini S, Selvi E, Capecchi PL, Chindamo D, Bisogno S, et al. Simvastatin inhibits cytokine production and nuclear factor-κB activation in interleukin 1β-stimulated synoviocytes from rheumatoid arthritis patients. Clinical and Experimental Rheumatology 2007;25(5):696-700.
  40. Li M, Yang X, Zhang Y, Chen L, Lu H, Li X, et al. Activation of protease-activated receptor-2 is associated with increased expression of inflammatory factors in the adipose tissues of obese mice. Mol Med Rep 2015;12(4):6227-34. https://doi.org/10.3892/mmr.2015.4179
  41. Ferrell WR, Lockhart JC, Kelso EB, Dunning L, Plevin R, Meek SE, et al. Essential role for proteinase-activated receptor-2 in arthritis. J Clin Invest 2003;111(1):35-41. https://doi.org/10.1172/JCI16913
  42. Cryer B, Dubois A. The advent of highly selective inhibitors of cyclooxygenase-a review. Prostaglandins Other Lipid Mediat 1998;56(5-6):341-61. https://doi.org/10.1016/S0090-6980(98)00064-1
  43. Laine L, Takeuchi K, Tarnawski A. Gastric mucosal defense and cytoprotection: bench to bedside. Gastroenterology 2008;135(1):41-60. https://doi.org/10.1053/j.gastro.2008.05.030
  44. Sorenseon O, Cowland JB, Askaa J, Borregaard N. An ELISA for hCAP-18, the cathelicidin present in human neutrophils and plasma. J Immunol Methods 1997;206(1-2):53-9. https://doi.org/10.1016/S0022-1759(97)00084-7
  45. Hase K, Eckmann L, Leopard JD, Varki N, Kagnoff MF. Cell differentiation is a key determinant of cathelicidin LL-37/human cationic antimicrobial protein 18 expression by human colon epithelium. Infection and Immunity 2002;70(2):953-63. https://doi.org/10.1128/iai.70.2.953-963.2002
  46. Ip YT, Davis RJ. Signal transduction by the c-Jun N-terminal kinase (JNK) - from inflammation to development. Current Opinion in Cell Biology 1998;10(2):205-19. https://doi.org/10.1016/S0955-0674(98)80143-9
  47. Choi BH, Hur EM, Lee JH, Jun DJ, Kim KT. Protein kinase C delta-mediated proteasomal degradation of MAP kinase phosphatase-1 contributes to glutamate-induced neuronal cell death. J Cell Sci 2005;119(Pt 7):1329-40.
  48. Oh HL, Seok JY, Kwon CH, Kang SK, Kim YK. Role of MAPK in ceramide-induced cell death in primary cultured astrocytes from mouse embryonic brain. NeuroToxicology 2006;27(1):31-8. https://doi.org/10.1016/j.neuro.2005.05.008
  49. Chuang SM, Wang IC, Yang JL. Roles of JNK, p38 and ERK mitogen-activated protein kinases in the growth inhibition and apoptosis induced by cadmium. Carcinogenesis 2000;21(7):1423-32. https://doi.org/10.1093/carcin/21.7.1423
  50. Porter AG, Janicke RU. Emerging roles of caspase-3 in apoptosis. Cell Death & Differentiation 1999;6(2):99-104. https://doi.org/10.1038/sj/cdd/4400476
  51. Stover EH, Borthwick KJ, Bavalia C, Eady N, Fritz DM, Rungroj N, et al. Novel ATP6V1B1 and ATP6V0A4 mutations in autosomal recessive distal renal tubular acidosis with new evidence for hearing loss. J Med Genet 2002;39(11):796-803. https://doi.org/10.1136/jmg.39.11.796
  52. Finberg KE, Wagner CA, Bailey MA, Paunescu TG, Breton S, Brown D, et al. The B1-subunit of the H+ ATPase is required for maximal urinary acidification. PNAS 2005;102(38):13616-21. https://doi.org/10.1073/pnas.0506769102
  53. Czepielewski RS, Porto BN, Rizzo LB, Roesler R, Abujamra AL, Pinto LG, et al. Gastrin-releasing peptide receptor (GRPR) mediates chemotaxis in neutrophils. PNAS 2012;109(2):547-52. https://doi.org/10.1073/pnas.1110996109
  54. Petronilho F, Danielski LG, Roesler R, Schwartsmann G, Dal-Pizzol F. Gastrin-releasing peptide as a molecular target for inflammatory diseases: an update. Inflamm Allergy Drug Targets 2013;12(3):172-7. https://doi.org/10.2174/1871528111312030003
  55. Pederson RA, Kwok YN, Coy DH. Gastrin secretion from human antral G cells in culture. Gastroenterology 1990;99(1):36-44. https://doi.org/10.1016/0016-5085(90)91226-v
  56. Foxx-Orenstein AE, Kuemmerle JF, Grider JR. Distinct 5-HT receptors mediate the peristaltic reflex induced by mucosal stimuli in human and guinea pig intestine. Gastroenterology 1996;111(5):1281-90. https://doi.org/10.1053/gast.1996.v111.pm8898642
  57. Kim DY, Camilleri M. Serotonin: A mediator of the brain-gut connection. Am J Gastroenterol 2000;95(10):2698-709.
  58. Jin JG, Foxx-Orenstein AE, Grider JR. Propulsion in guinea pig colon induced by 5-hydroxytryptamine (HT) via 5-HT4 and 5-HT3 receptors. J Pharmacol Exp Ther 1998;288(1):93-7.
  59. Keast JR, Furness JB, Costs M. Distribution of certain peptide YY containing nerve fibers and endocrine cells in the gastrointestinal mucosa in five mammalian species. J Comp Neurol 1985;263(3):403-22. https://doi.org/10.1002/cne.902360308
  60. Allen JM, Gu KJ, Adrian TE, Polak JM, Bloom SR. Neuropeptide Y in the guinea pig biliary tract. Experientia 1984;40(7):765-7. https://doi.org/10.1007/BF01949769
  61. Park JG, Hyun JW, Lim KW, Shin JE, Won YJ, Shin KH, et al. Antineoplastic Effect of Extracts from Traditional Medicinal Plants. The Korean Society of Pharmacognosy 1993;24(3):223-30.
  62. Nam GH, Jo KJ, Park YS, Kwak HW, Wee JH, Kim JH, et al. Anti-cancer Effect of Cinnamomum camphora Ethanol Extract by Double Induction of Apoptotic and Autophagic Cell Death in HCT 116 and HT-29 Human Colon Cancer Cell through the mTOR Signaling Pathway. Korean Society for Biotechnology and Bioengineering Journal 2019;34(2):114-9.
  63. Jin Z, El-Deiry WS. Overview of cell death signaling pathways. Cancer Biol Ther 2005;4(2):147-71. https://doi.org/10.4161/cbt.4.2.1508
  64. Okada H, Mak TW. Pathways of apoptotic and non-apoptotic death in tumour cells. Nat Rev Cancer 2004;4(8):592-603. https://doi.org/10.1038/nrc1412