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마우스 만성 췌장염 모델에서 연교(連翹)와 현호색(玄胡索) 단일 추출물 및 추출 혼합물의 보호 효과

Protective Effects of Individual Extract and Mixture of Forsythia Fructus and Corydalis Tuber on Chronic Pancreatitis in Mice

  • 신준연 (원광대학교 한의과대학 본초학교실) ;
  • 최지원 (원광대학교 한의과대학 본초학교실) ;
  • 김동욱 (원광대학교 한방심신증후군센터) ;
  • 주자기 (원광대학교 한의과대학 본초학교실) ;
  • 권빛나 (원광대학교 한의과대학 본초학교실) ;
  • 배기상 (원광대학교 한방심신증후군센터) ;
  • 송호준 (원광대학교 한의과대학 본초학교실) ;
  • 박성주 (원광대학교 한의과대학 본초학교실)
  • Shin, Joon Yeon (Department of Herbology, School of Korean Medicine, Wonkwang University) ;
  • Choi, Ji-Won (Department of Herbology, School of Korean Medicine, Wonkwang University) ;
  • Kim, Dong-Uk (Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University) ;
  • Zhou, Ziqi (Department of Herbology, School of Korean Medicine, Wonkwang University) ;
  • Kweon, Bitna (Department of Herbology, School of Korean Medicine, Wonkwang University) ;
  • Bae, Gi-Sang (Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University) ;
  • Song, Ho-Joon (Department of Herbology, School of Korean Medicine, Wonkwang University) ;
  • Park, Sung-Joo (Department of Herbology, School of Korean Medicine, Wonkwang University)
  • 투고 : 2020.11.04
  • 심사 : 2021.01.25
  • 발행 : 2021.01.30

초록

Objectives : Forsythiae Fructus has been reported to have anti-inflammatory effects in many diseases, and Corydalis Tuber has been used as a pain suppressor in Eastern Asia. However, the protective effects of individual water extract of Forsythiae Fructus (FF) and Corydalis Tuber (CT) and the mixture of FF and CT (FC) on chronic pancreatitis (CP) were not well-investigated. Therefore, we investigated the protective effects of FF, CT, and FC on CP in mice. Methods : To induce CP, cerulein was injected 6 times a day, 4 times a week for 3 weeks. 1 h before the every cerulein injection, 200 mg/kg of FF, CT, or FC was intraperitoneally injected to mice. Histological analysis of pancreas was examined by hematoxylin and eosin stain and collagen deposition was examined by Masson's trichrome stain. Fibrogenic parameters such as α-smooth muscle actin (α-SMA), extracellular matrix (ECM) deposition, and fibrotic cytokines such as transforming growth factor (TGF)-β1 and platelet-derived growth factor (PDGF) were also analyzed by immunofluorescence stain and real-time PCR. Results : Histological damages in pancreas were inhibited by pre-treatment of FF or FC but not CT. α-SMA and ECM in pancreas were inhibited by pre-treatment of CT or FC but not FF. Moreover, the expression of TGF-β1 and PDGF in pancreas were inhibited by FF, CT or FC. Conclusions : Our results suggest that FC have protective effect on CP in mice through inhibition of α-SMA, ECM, TGF-β1 and PDGF in pancreas, and these findings could suggest new clinical strategy for CP.

키워드

참고문헌

  1. Choi JW, Lee SK, Kim MJ, Kim DG, Shin JY, Zhou Z, Jo IJ, Song HJ, Bae GS, Park SJ. Piperine ameliorates the severity of fibrosis via inhibition of TGFβ/SMAD signaling in a mouse model of chronic pancreatitis. Mol Med Rep. 2019 ; 20(4) : 3709-18.
  2. Conwell DL, Lee LS, Yadav D, Longnecker DS, Miller FH, Mortele KJ, Levy MJ, Kwon R, Lieb JG, Stevens T, Toskes PP, Gardner TB, Gelrud A, Wu BU, Forsmark CE, Vege SS. American Pancreatic Association Practice Guidelines in Chronic Pancreatitis: evidence-based report on diagnostic guidelines. Pancreas. 2014 ; 43(8) : 1143-62. https://doi.org/10.1097/MPA.0000000000000237
  3. Etemad B, Whitcomb DC. Chronic pancreatitis: diagnosis, classification, and new genetic developments. Gastroenterology. 2001 ; 120(3) : 682-707. https://doi.org/10.1053/gast.2001.22586
  4. Conwell DL, Banks PA, Sandhu BS, Sherman S, Al-Kaade S, Gardner TB, Anderson MA, Wilcox CM, Lewis MD, Muniraj T, Forsmark CE, Cote GA, Guda NM, Tian Y, Romagnuolo J, Wisniewski SR, Brand R, Gelrud A, Slivka A, Whitcomb DC, Yadav D. Validation of Demographics, Etiology, and Risk Factors for Chronic Pancreatitis in the USA: A Report of the North American Pancreas Study (NAPS) Group. Dig Dis Sci. 2017 ; 62(8) : 2133-40. https://doi.org/10.1007/s10620-017-4621-z
  5. Hart PA, Conwell DL. Chronic Pancreatitis: Managing a Difficult Disease. Am J Gastroenterol. 2020 ; 115(1) : 49-55. https://doi.org/10.14309/ajg.0000000000000421
  6. Bouwense SA, Olesen SS, Drewes AM, Poley JW, van Goor H, Wilder-Smith OH. Effects of pregabalin on central sensitization in patients with chronic pancreatitis in a randomized, controlled trial. PLoS One. 2012 ; 7(8) : e42096. https://doi.org/10.1371/journal.pone.0042096
  7. Deviere J, Bell RH Jr, Beger HG, Traverso LW. Treatment of chronic pancreatitis with endotherapy or surgery: critical review of randomized control trials. J Gastrointest Surg. 2008 ; 12(4) : 640-4. https://doi.org/10.1007/s11605-007-0448-9
  8. Worning H. Alcoholic chronic pancreatitis. In: Bergen HG, eds. The pancreas vol 1. 1st ed. Malden : Blackwell Science. 1998 : 677-82.
  9. Steer ML, Waxman I, Freedman S. Chronic pancreatitis. N Engl J Med. 1995 ; 332(22) : 1482-90. https://doi.org/10.1056/NEJM199506013322206
  10. Mullady DK, Yadav D, Amann ST, O'Connell MR, Barmada MM, Elta GH, Scheiman JM, Wamsteker EJ, Chey WD, Korneffel ML, Weinman BM, Slivka A, Sherman S, Hawes RH, Brand RE, Burton FR, Lewis MD, Gardner TB, Gelrud A, DiSario J, Baillie J, Banks PA, Whitcomb DC, Anderson MA; NAPS2 Consortium. Type of pain, pain-associated complications, quality of life, disability and resource utilisation in chronic pancreatitis: a prospective cohort study. Gut. 2011 ; 60(1) : 77-84. https://doi.org/10.1136/gut.2010.213835
  11. Lieb JG 2nd, Forsmark CE. Review article: pain and chronic pancreatitis. Aliment Pharmacol Ther. 2009 ; 29(7) : 706-19. https://doi.org/10.1111/j.1365-2036.2009.03931.x
  12. Pezzilli R. Pain in chronic pancreatitis: from the bench to the bedside. JOP. 2012 ; 13(2) : 245-6.
  13. Aghdassi AA, Mayerle J, Christochowitz S, Weiss FU, Sendler M, Lerch MM. Animal models for investigating chronic pancreatitis. Fibrogenesis Tissue Repair. 2011 ; 4(1) : 26. https://doi.org/10.1186/1755-1536-4-26
  14. The National College of Korean Medicine Spleen System International Medicine classroom. Spleen System International Medicine. Seoul : Koonja. 2009 : 435-8.
  15. Lee JM, Choi SW, Cho SH, Rhee SJ. Effect of Forsythia Viridissima Extracts on Antioxidative System and Lipid Peroxidation of Liver in Rats Fed High-Cholesterol Diet. J Nutr Health. 2003 ; 36(10) : 990-6.
  16. Yoon SJ, Kim YS. Effect of Corydalidis Tuber. Carthami Flos. Paeoniae Radix Rubra on Anti-Inflamation and function of the Liver at Arthritis Rats. J Physiol & Pathol Korean Med. 2005 ; 19(2) : 475-80.
  17. Li ZX, Wang XH, Zhao JH, Yang JF, Wang X. [Investigation on antibacterial activity of Forsythia suspense Vahl in vitro with Mueller-Hinton agar]. Zhongguo Zhong Yao Za Zhi. 2000 ; 25(12) : 742-5.
  18. Vlietinck AJ, De Bruyne T, Apers S, Pieters LA. Plant-derived leading compounds for chemotherapy of human immunodeficiency virus (HIV) infection. Planta Med. 1998 ; 64(2) : 97-109. https://doi.org/10.1055/s-2006-957384
  19. Kim SY, Park YK. Ethanol Extract of Forsythiae Fructus Inhibits the Production of Inflammatory Mediators in LPS-stimulated BV-2 Microglial Cells. Kor. J. Herbology. 2008 ; 23(3) : 93-102.
  20. Park YA, Kim DC. Corydalis Tuber Induces Apoptosis in MCF-7 Cells, Via Inhibition of Bcl-2 and Bcl-XL Expression. The Journal of Oriental Obstetrics & Gynecology. 2008 : 21(4) : 90-103.
  21. Lee KY, Park SK, Kim JS, Jang MH, Kim CJ, Choi SM, Lee HJ, Kim EH. Effects of Corydalis Tuber on Synthesis of NO and PGE2 in Murine Macrophage RAW 264.7 Cells Stimulated by LPS. J Physiol & Pathol Korean Med. 2005 ; 19(3) : 785-91.
  22. Van Laethem JL, Robberecht P, Resibois A, Deviere J. Transforming growth factor beta promotes development of fibrosis after repeated courses of acute pancreatitis in mice. Gastroenterology. 1996 ; 110(2) : 576-82. https://doi.org/10.1053/gast.1996.v110.pm8566606
  23. Choi JW, Jeong JH, Jo IJ, Kim DG, Shin JY, Kim MJ, Choi BM, Shin YK, Song HJ, Bae GS, Park SJ. Preventive Effects of Gardenia jasminoides on Cerulein-Induced Chronic Pancreatitis. Am J Chin Med. 2020 ; 48(4) : 987-1003. https://doi.org/10.1142/s0192415x20500470
  24. Masamune A, Watanabe T, Kikuta K, Shimosegawa T. Roles of pancreatic stellate cells in pancreatic inflammation and fibrosis. Clin Gastroenterol Hepatol. 2009 ; 7(11 Suppl) : S48-54. https://doi.org/10.1016/j.cgh.2009.07.038
  25. Apte M, Pirola R, Wilson J. The fibrosis of chronic pancreatitis: new insights into the role of pancreatic stellate cells. Antioxid Redox Signal. 2011 ; 15(10) : 2711-22. https://doi.org/10.1089/ars.2011.4079
  26. Apte M, Norton I, Haber P, Applegate T, Korsten M, McCaughan G, Pirola R, Wilson J. The effect of ethanol on pancreatic enzymes--a dietary artefact? Biochim Biophys Acta. 1998 ; 1379(3) : 314-24. https://doi.org/10.1016/S0304-4165(97)00109-8
  27. Vinokurova LV, Zhivaeva NS, Tsaregorodtseva TM, Serova TI. [A cytokine status in chronic alcoholic and biliary pancreatitis]. Ter Arkh. 2006 ; 78(2) : 57-60.
  28. Mokrowiecka A, Pinkowski D, Malecka-Panas E. Assessment of quality of life in patients with chronic pancreatitis. Med Sci Monit. 2011 ; 17(10) : CR583-8.
  29. Nojgaard C, Becker U, Matzen P, Andersen JR, Holst C, Bendtsen F. Progression from acute to chronic pancreatitis: prognostic factors, mortality, and natural course. Pancreas. 2011 ; 40(8) : 1195-200. https://doi.org/10.1097/MPA.0b013e318221f569
  30. Umapathy C, Raina A, Saligram S, Tang G, Papachristou GI, Rabinovitz M, Chennat J, Zeh H, Zureikat AH, Hogg ME, Lee KK, Saul MI, Whitcomb DC, Slivka A, Yadav D. Natural History After Acute Necrotizing Pancreatitis: a Large US Tertiary Care Experience. J Gastrointest Surg. 2016 ; 20(11) : 1844-53. https://doi.org/10.1007/s11605-016-3264-2
  31. Yadav D, O'Connell M, Papachristou GI. Natural history following the first attack of acute pancreatitis. Am J Gastroenterol. 2012 ; 107(7) : 1096-103. https://doi.org/10.1038/ajg.2012.126
  32. Kim SY, Park YK. Ethanol extract of Forsythiae Fructus inhibits the production of inflammtory mediators in LPS-stimulated BV-2 microglia cells. Kor J Herbology. 2008 ; 23(3) : 93-102.
  33. Kou X, Qi S, Dai W, Luo D, Yin Z. Arctigenin inhibits lipopolysaccharide-induced iNOS expression in RAW264.7 cells through suppressing JAK-STAT signal pathway. Int Immunopharmacol. 2011 ; 11(8) : 1095-102. https://doi.org/10.1016/j.intimp.2011.03.005
  34. Jung HW, Mahesh R, Lee JG, Lee SH, Kim YS, Park YK. Pinoresinol from the fruits of Forsythia koreana inhibits inflammatory responses in LPS-activated microglia. Neurosci Lett. 2010 ; 480(3) : 215-20. https://doi.org/10.1016/j.neulet.2010.06.043
  35. Arjumand W, Seth A, Sultana S. Rutin attenuates cisplatin induced renal inflammation and apoptosis by reducing NFκB, TNF-α and caspase-3 expression in wistar rats. Food Chem Toxicol. 2011 ; 49(9) : 2013-21. https://doi.org/10.1016/j.fct.2011.05.012
  36. Hausmann M, Obermeier F, Paper DH, Balan K, Dunger N, Menzel K, Falk W, Schoelmerich J, Herfarth H, Rogler G. In vivo treatment with the herbal phenylethanoid acteoside ameliorates intestinal inflammation in dextran sulphate sodium-induced colitis. Clin Exp Immunol. 2007 ; 148(2) : 373-81. https://doi.org/10.1111/j.1365-2249.2007.03350.x
  37. Kin KC, Hsu B. Study on the pharmacological actions of Corydalis I. Analgesic action of Cordalis A, B and L. Acta Physiol Sin. 1957 ; 21 : 150-7.
  38. Chang CK, Lin MT. DL-Tetrahydropalmatin may act through inhibition of amygdaloid release of dopamine to inhibit an epileptic attack in rats. Neurosci Lett. 2001 ; 307 : 163-6. https://doi.org/10.1016/S0304-3940(01)01962-0
  39. Haber PS, Keogh GW, Apte MV, Moran CS, Stewart NL, Crawford DH, Pirola RC, McCaughan GW, Ramm GA, Wilson JS. Activation of pancreatic stellate cells in human and experimental pancreatic fibrosis. Am J Pathol. 1999 ; 155(4) : 1087-95. https://doi.org/10.1016/S0002-9440(10)65211-X
  40. Luttenberger T, Schmid-Kotsas A, Menke A, Siech M, Beger H, Adler G, Grunert A, Bachem MG. Platelet-derived growth factors stimulate proliferation and extracellular matrix synthesis of pancreatic stellate cells: implications in pathogenesis of pancreas fibrosis. Lab Invest. 2000 ; 80(1) : 47-55. https://doi.org/10.1038/labinvest.3780007
  41. Masamune A, Suzuki N, Kikuta K, Ariga H, Hayashi S, Takikawa T, Kume K, Hamada S, Hirota M, Kanno A, Egawa S, Unno M, Shimosegawa T. Connexins regulate cell functions in pancreatic stellate cells. Pancreas. 2013 ; 42(2) : 308-16. https://doi.org/10.1097/MPA.0b013e31825c51d6