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The Protective Effect of Arecae Semen and Coptidis Rhizoma in a Chronic Reflux Esophagitis Rat Model

만성 역류성 식도염 모델에서 빈랑(檳榔)와 황련(黃連) 복합물의 보호 효과

  • Lee, Se Hui (Dept. of Herbology, College of Korean Medicine, Daegu Haany University) ;
  • Lee, Jin A (Dept. of Herbology, College of Korean Medicine, Daegu Haany University) ;
  • Shin, Mi-Rae (Dept. of Herbology, College of Korean Medicine, Daegu Haany University) ;
  • Lee, Ji Hye (Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine) ;
  • Roh, Seong-Soo (Dept. of Herbology, College of Korean Medicine, Daegu Haany University)
  • 이세희 (대구한의대학교 한의과대학 본초약리학교실) ;
  • 이진아 (대구한의대학교 한의과대학 본초약리학교실) ;
  • 신미래 (대구한의대학교 한의과대학 본초약리학교실) ;
  • 이지혜 (한국한의학연구원 한약자원연구센터) ;
  • 노성수 (대구한의대학교 한의과대학 본초약리학교실)
  • Received : 2021.02.16
  • Accepted : 2021.04.05
  • Published : 2021.03.30

Abstract

Objective: Chronic reflux esophagitis (CRE), characterized by esophageal mucosa ulcer, is caused by continuous backflow of gastric acid and consequent inflammation due to unstable gastroesophageal sphincter. The aim of the present study was to clarify the effect of an Arecae Semen and Coptidis Rhizoma mixture (AC-mix) on CRE. Methods: CRE was surgically induced in SD rats with three experimental groups used: normal; CRE control; and CRE treatment (200 mg/kg AC-mix). Blood and esophageal tissue were collected after two weeks of drug administration. The anti-oxidant activity of the AC-mix was measured by total polyphenol and total flavonoid contents as well as by radical scavenging activity with protein levels evaluated using western blotting. Results: CRE damage to the esophageal mucosa was significantly reduced in the AC-mix group as compared with the controls, and administration of the AC-mix was seen to inhibit NF-κBp65 activity. Consequently, the inactivation of NF-κBp65 significantly inhibited inflammatory mediators such as COX-2 and iNOS. Moreover, the anti-oxidant enzyme HO-1 significantly increased through activation of the Nrf2-Keap1 pathway. Matrix metalloproteinase-2 (MMP-2), which can break down collagen from the basement membrane and extracellular matrix, was decreased following AC-mix treatment, and elevated levels of MMP-2 were regulated by its tissue inhibitor. Conclusions: These results show that AC-mix can alleviate esophageal mucosa ulcer though inhibition of the NF-κBp65 inflammatory pathway and enhancement of the anti-oxidant Nrf2-Keap1 pathway.

Keywords

References

  1. Jeon SG, Rhee PL. Prevalence, Clinical Manifestations, and Treatment of Gastroesophageal Reflux Disease in Korea. The Korean Journal of Gastroenterology 2002;39(6):393-401.
  2. Lee SH. A Comparative Study on the Effects of Pinellia ternata, Zingiber officinale and Sobanhatang on Reflux Esophagit. Sangji University Graduate School 2017.
  3. Kethman W, Hawn M. New Approaches to Gastroesophageal Reflux Disease. Journal of Gastrointestinal Surgery 2017;16(6):1544-52. https://doi.org/10.1007/s11605-017-3439-5
  4. Jang MW, Lim SW. Experimental Study for Effect of Banhasasim-tang on Mice with Reflux Esophagitis. The journal of internal Korean medicine 2013;34(4):362-74.
  5. Sandhu DS, Fass R. Current Trends in the Management of Gastroesophageal Reflux Disease. Gut Liver 2017;12(1):7-16. https://doi.org/10.5009/gnl16615
  6. Jang HJ. Clinical characteristics of gastroesophageal reflux disease and the risk factors for erosive esophagitis. Gyeongsang National University Graduate School 2009.
  7. Castell DO, Murray JA, Tutuian R, Orlando RC, Arnold R. Review article: the pathophysiology of gastro-oesophageal reflux disease - oesophageal manifestations. Alimentary Pharmacology & Therapeutics 2004;20(9):14-25.
  8. Colin-Jones DG. Histamine-2-receptor antagonists in gastroesophageal reflux. Gut 1989;30(10):1305-8. https://doi.org/10.1136/gut.30.10.1305
  9. DeVault KR, Castell DO. Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease. American Journal Gastroenterol 1999;94(6):1434-42. https://doi.org/10.1016/S0002-9270(99)00179-3
  10. Klinkenberg-Knol EC, Jansen JMBJ, Festen HPM, Meuwissen SG, Lamers CB. Double-blind multicentre comparison of omeprazole and ranitidine in the treatment of reflux esophagitis. Lancet 1987;329(8529):349-51. https://doi.org/10.1016/S0140-6736(87)91726-0
  11. Spechler SJ. Comparison of medical and surgical therapy for complicated gastroesophageal reflux disease in Veteran. The New England Journal of Medicine 1992;326:786-92. https://doi.org/10.1056/NEJM199203193261202
  12. Lee KS, Kim SH, Chun SH, Park SS, Park CS, Shin YS. Antimicrobial Activity of Areca catachu L. Extract of against Intestinal Pathogens. The Korean Society of Food Science and Nutrition 1998;11(1):36-40.
  13. 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. The Korea Journal of Herbology 2019;34(1):117-24. https://doi.org/10.6116/KJH.2019.34.1.117
  14. Kim BW. Effects of Hwangryeun Extract on the Recovery of Liver Function in CCl4-exposed Rat. Journal of Physiology & Pathology in Korea Medicine 2011;25(6):1020-5.
  15. Go YJ, Kim YE, Kim HN, Lee EH, Cho EB, Akhmadjon S, et al. Inhibition effect against elastase, collagenase, hyaluronidase and anti-oxidant activity of thinning Green ball apple. The Korean Society for Applied Biological Chemistry 2020;63(1):43-50.
  16. Lister CE, Lancaster JE, Sutton KH, Walker JR. Developmental changes in the concentration and composition of flavonoids in skin of a red and a green apple cultivar. Journal of the science of food and agriculture 1994;64(2):155-61. https://doi.org/10.1002/jsfa.2740640204
  17. Blois MS. Antioxidant Determinations by the Use of a Stable Free Radical. Nature 1958;181:1199-200. https://doi.org/10.1038/1811199a0
  18. Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorizationassay. Free Radical Biology and Medicine 1999;26(9-10):1231-7. https://doi.org/10.1016/S0891-5849(98)00315-3
  19. 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
  20. Han CH, Lee JS, Lim HH, Oh YS, Yoon YK, Kim SG, et al. The Significance of Gastroesophageal Reflux Disease (GERD) Symptoms in Patients with Reflux Esophagitis. Journal of Neurogastroenterology and Motility 2000;6(2):196-205.
  21. Giri AK, Rawat JK, Singh M, Gautam S, Kaithwas G. Effect of lycopene against gastroesophageal reflux disease in experimental animals. BioMed Central Complement Altern Med 2015;15:110. https://doi.org/10.1186/s12906-015-0631-6
  22. Choi SY, Kim JH, Lee JM, Lee SH, Cho EJ. Protective effect of Acer okamotoanum from oxidative stress in C6 glial cells. Journal of applied biological chemistry 2017;60(2):141-7. https://doi.org/10.3839/jabc.2017.024
  23. Jaramillo MC, Zhang DD. The emerging role of the Nrf2-Keap1 signaling pathway in cancer. Genes & Development 2013;27(20):2179-91. https://doi.org/10.1101/gad.225680.113
  24. Kobayashi M, Yamamoto M. Molecular mechanisms activating the Nrf2-Keap1 pathway of antioxidant gene regulation. Antioxidants & Redox Signaling 2005;7(3-4):385-94. https://doi.org/10.1089/ars.2005.7.385
  25. Lim JS. Expression of Nrf2 Transcription Factor in Rat Kidney. Chonnam National University Graduate School 2009.
  26. Li L, Grenard P, Nhieu JT, Julien B, Mallat A, Habib A, et al. Heme oxygenase-1 is an antifibrogenic protein in human hepatic myofibrobalsts. Gastroenterology 2003;125(2):460-9. https://doi.org/10.1016/S0016-5085(03)00906-5
  27. Nakao A, Otterbein LE, Overhaus M, Sarady JK, Tsung A, Kimizuka K, et al. Biliverdin protects the functional integrity of a transplanted syngeneic small bowel. Gastroenterology 2004;127(2):595-606. https://doi.org/10.1053/j.gastro.2004.05.059
  28. Lee HS. Suppressive effect of chlorella on oxidative stress and NFkB activity. Inje University Graduate School 2003.
  29. Funk CD. Prostaglandins and leukotrienes; Advances in eicosanoid biology. Science 2001;294(5548):1871-5. https://doi.org/10.1126/science.294.5548.1871
  30. Shon DH, Choi DW, Kim MH. Improvement of anti-inflammation activity of Gardeniae fructus extract by the tratment of β-Glucisudase. Korean Society of Food Science and Technology 2012;44(3):331-6. https://doi.org/10.9721/KJFST.2012.44.3.331
  31. Hippeli S, Elstner EF. Inhibition of biochemical model reactions for inflammatory processes by plant extracts: a review on recent developments. Free Radical Research 1999;31(1):81-7. https://doi.org/10.1080/10715769900301361
  32. McCartney-Francis N, Allen JB, Mizel DE, Albina JE, Xie QW, Nathan CF, et al. 1993. Suppression of arthritis by an inhibitor of nitric oxide synthase. Journal of Experimental Medicine 1993;178(2):749-54. https://doi.org/10.1084/jem.178.2.749
  33. Kim JO, Lee CW, Kim EK, Lee SJ, Park NH, Kim HS, et al. Inhibition effect of Gynura procumbens extract on UV-B-induced matrix-metalloproteinase expression in human dermal fibroblasts. Journal Ethnopharmacol 2011;137(1):427-33. https://doi.org/10.1016/j.jep.2011.04.072
  34. Hwang YP, Choi JH, Kim HG, Choi JM, Hwang SK, Chung YC, et al. Cultivated ginseng suppresses ultraviolet B-induced collagenase activation via mitogen-activated protein kinases and nuclear factor NFκB/activator protein-1-dependent signaling in human dermal fibroblasts. Nutrition Research 2012;32(6):428-38. https://doi.org/10.1016/j.nutres.2012.04.005
  35. Johnson MD, Kim HR, Chesler L, Tsao-Wu G, Bouck N, Polverini PJ. Inhibition of angiogenesis by tissue inhibitor of metalloproteinase. Journal of Cellular Physiology 1994;160(1):194-202. https://doi.org/10.1002/jcp.1041600122
  36. 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
  37. 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.