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Anti-microbial and anti-inflammatory effects of Cheonwangbosim-dan against Helicobacter pylori-induced gastritis

  • Park, Hee-Seon (Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University) ;
  • Jeong, Hye-Yun (Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University) ;
  • Kim, Young-Suk (Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University) ;
  • Seo, Chang-Seob (Herbal Medicine Research Division, Korea Institute of Oriental Medicine) ;
  • Ha, Hyekyung (Herbal Medicine Research Division, Korea Institute of Oriental Medicine) ;
  • Kwon, Hyo-Jung (Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University)
  • 투고 : 2019.10.10
  • 심사 : 2020.01.26
  • 발행 : 2020.05.31

초록

Background: There are various Helicobacter species colonizing the stomachs of animals. Although Helicobacter species usually cause asymptomatic infection in the hosts, clinical signs can occur due to gastritis associated with Helicobacter in animals. Among them, Helicobacter pylori is strongly associated with chronic gastritis, gastric ulcers, and gastric cancers. As the standard therapies used to treat H. pylori have proven insufficient, alternative options are needed to prevent and eradicate the diseases associated with this bacterium. Cheonwangbosim-dan (CBD), a traditional herbal formula that is popular in East Asia, has been commonly used for arterial or auricular flutter, neurosis, insomnia, and cardiac malfunction-induced disease. Objectives: The present study investigated the antimicrobial effect of CBD on H. pylori-infected human gastric carcinoma AGS cells and model mice. Methods: AGS cells were infected with H. pylori and treated with a variety of concentrations of CBD or antibiotics. Mice were given 3 oral inoculations with H. pylori and then dosed with CBD (100 or 500 mg/kg) for 4 weeks or with standard antibiotics for 1 week. One week after the last treatment, gastric samples were collected and examined by histopathological analysis, real-time quantitative polymerase chain reaction, and immunoblotting. Results: Our results showed that CBD treatment of AGS cells significantly reduced the H. pylori-induced elevations of interleukin-8, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). In the animal model, CBD treatment inhibited the colonization of H. pylori and the levels of malondialdehyde, inflammation, proinflammatory cytokines, iNOS, and COX-2 in gastric tissues. CBD also decreased the phosphorylation levels of p38 mitogen-activated protein kinase family. Conclusions: This study suggests that CBD might be a prospective candidate for treating H. pylori-induced gastric injury.

키워드

과제정보

The present research was supported by a grant from the Korea Institute of Oriental Medicine (KIOM; Evaluation of Herb-Drug Interactions, K16252).

참고문헌

  1. Hooi JKY, Lai WY, Ng WK, Suen MMY, Underwood FE, Tanyingoh D, Malfertheiner P, Graham DY, Wong VWS, Wu JCY, Chan FKL, Sung JJY, Kaplan GG, Ng SC. Global prevalence of Helicobacter pylori infection: systematic review and meta-analysis. Gastroenterology. 2017;153(2):420-429. https://doi.org/10.1053/j.gastro.2017.04.022
  2. Eusebi LH, Zagari RM, Bazzoli F. Epidemiology of Helicobacter pylori infection. Helicobacter. 2014;19 Suppl 1:1-5. https://doi.org/10.1111/hel.12165
  3. O'Connor A, Lamarque D, Gisbert JP, O'Morain C. Treatment of Helicobacter pylori infection 2017. Helicobacter. 2017;22 Suppl 1.
  4. Ayala G, Escobedo-Hinojosa WI, de la Cruz-Herrera CF, Romero I. Exploring alternative treatments for Helicobacter pylori infection. World J Gastroenterol. 2014;20(6):1450-1469. https://doi.org/10.3748/wjg.v20.i6.1450
  5. Haesebrouck F, Pasmans F, Flahou B, Chiers K, Baele M, Meyns T, Decostere A, Ducatelle R.Gastric helicobacters in domestic animals and nonhuman primates and their significance for human health. Clin Microbiol Rev. 2009;22(2):202-223. https://doi.org/10.1128/CMR.00041-08
  6. Sykes J, Greene C. Infectious Diseases of the Dog and Cat. 4th ed. St. Louis: Saunders; 2012, p 374-380.
  7. Neiger R, Simpson KW. Helicobacter infection in dogs and cats: facts and fiction. J Vet Intern Med. 2000;14(2):125-133. https://doi.org/10.1892/0891-6640(2000)014<0125:IIDACF>2.3.CO;2
  8. Sharma SA, Tummuru MK, Miller GG, Blaser MJ. Interleukin-8 response of gastric epithelial cell lines to Helicobacter pylori stimulation in vitro. Infect Immun. 1995;63(5):1681-1687. https://doi.org/10.1128/iai.63.5.1681-1687.1995
  9. Handa O, Naito Y, Yoshikawa T. Helicobacter pylori: a ROS-inducing bacterial species in the stomach. Inflamm Res. 2010;59(12):997-1003. https://doi.org/10.1007/s00011-010-0245-x
  10. Tiwari SK, Manoj G, Sharma V, Sivaram G, Saikant R, Bardia A, Sharma VK, Abid Z, Khan AA, Habeeb MA, Habibullah CM, Kumar BS, Nandan A. Relevance of Helicobacter pylori genotypes in gastric pathology and its association with plasma malondialdehyde and nitric oxide levels. Inflammopharmacology. 2010;18(2):59-64. https://doi.org/10.1007/s10787-010-0031-y
  11. Slomiany BL, Slomiany A. Induction in gastric mucosal prostaglandin and nitric oxide by Helicobacter pylori is dependent on MAPK/ERK-mediated activation of IKK-β and cPLA2: modulatory effect of ghrelin. Inflammopharmacology. 2013;21(3):241-251. https://doi.org/10.1007/s10787-013-0169-5
  12. Kim OS, Kim Y, Yoo SR, Lee MY, Shin HK, Jeong SJ. Cheonwangbosimdan, a traditional herbal formula, inhibits inflammatory responses through inactivation of NF-κB and induction of heme oxygenase-1 in raw264. 7 murine macrophages. Int J Clin Exp Med. 2016;9(2):1692-1699.
  13. Kim NJ, Kong YY, Chang SW. Studies on the efficacy of combined preparation of crude drugs (XXXVII). The effects of chunwangboshimdan on the central nervous system and cardio-vascular system. Korean J Pharmacogn. 1988;19(3):208-215.
  14. Kim B, Jo C, Choi HY, Lee K. Vasorelaxant and hypotensive effects of Cheonwangbosimdan in SD and SHR rats. Evid Based Complement Alternat Med. 2018;2018:6128604.
  15. Thompson LJ, Danon SJ, Wilson JE, O'Rourke JL, Salama NR, Falkow S, Mitchell H, Lee A. Chronic Helicobacter pylori infection with Sydney strain 1 and a newly identified mouse-adapted strain (Sydney strain 2000) in C57BL/6 and BALB/c mice. Infect Immun. 2004;72(8):4668-4679. https://doi.org/10.1128/IAI.72.8.4668-4679.2004
  16. Shinilbooks Committee. The Korean Herbal Pharmacopoeia. 5th ed. Seoul: Shinilbooks; 2016, p 458.
  17. Seo CS, Kim OS, Shin HK. Quantitative determination and antioxidant effects of Cheonwangbosimdan. Korean J Pharmacogn. 2014;45(4):300-314.
  18. Seo CS, Shin HK. Development and validation of a high-performance liquid chromatographic method for the simultaneous quantification of marker constituents in Cheonwangbosimdan. Nat Prod Commun. 2014;9(12):1751-1754.
  19. Park HS, Wijerathne CU, Jeong HY, Seo CS, Ha H, Kwun HJ. Gastroprotective effects of Hwanglyeonhaedok-tang against Helicobacter pylori-induced gastric cell injury. J Ethnopharmacol. 2018;216:239-250. https://doi.org/10.1016/j.jep.2018.01.025
  20. Crabtree JE, Lindley IJ. Mucosal interleukin-8 and Helicobacter pylori-associated gastroduodenal disease. Eur J Gastroenterol Hepatol. 1994;6 Suppl 1:S33-S38.
  21. Huang HL, Ko CH, Yan YY, Wang CK. Antiadhesion and anti-inflammation effects of noni (Morinda citrifolia) fruit extracts on AGS cells during Helicobacter pylori infection. J Agric Food Chem. 2014;62(11):2374-2383. https://doi.org/10.1021/jf405199w
  22. Drake IM, Mapstone NP, Schorah CJ, White KL, Chalmers DM, Dixon MF, Axon AT. Reactive oxygen species activity and lipid peroxidation in Helicobacter pylori associated gastritis: relation to gastric mucosal ascorbic acid concentrations and effect of H pylori eradication. Gut. 1998;42(6):768-771. https://doi.org/10.1136/gut.42.6.768
  23. Saeidi E, Sheikhshahrokh A. vacA genotype status of Helicobacter pylori isolated from foods with animal origin. Biomed Res Int. 2016;2016:8701067. https://doi.org/10.1155/2016/8701067
  24. Momtaz H, Dabiri H, Souod N, Gholami M. Study of Helicobacter pylori genotype status in cows, sheep, goats and human beings. BMC Gastroenterol. 2014;14(1):61. https://doi.org/10.1186/1471-230X-14-61
  25. Vega AE, Wendel GH, Maria AO, Pelzer L. Antimicrobial activity of Artemisia douglasiana and dehydroleucodine against Helicobacter pylori. J Ethnopharmacol. 2009;124(3):653-655. https://doi.org/10.1016/j.jep.2009.04.051
  26. Bonifacio BV, dos Santos Ramos MA, da Silva PB, Bauab TM. Antimicrobial activity of natural products against Helicobacter pylori: a review. Ann Clin Microbiol Antimicrob. 2014;13(1):54. https://doi.org/10.1186/PREACCEPT-1712290149140143
  27. Li MM, Wu LY, Zhao T, Xiong L, Huang X, Liu ZH, Fan XL, Xiao CR, Gao Y, Ma YB, Chen JJ, Zhu LL, Fan M. The protective role of 5-HMF against hypoxic injury. Cell Stress Chaperones. 2011;16(3):267-273. https://doi.org/10.1007/s12192-010-0238-2
  28. Kong F, Lee BH, Wei K. 5-hydroxymethylfurfural mitigates lipopolysaccharide-stimulated inflammation via suppression of MAPK, NF-κB and mTOR activation in RAW 264.7 cells. Molecules. 2019;24(2):275. https://doi.org/10.3390/molecules24020275
  29. Li C, Huang P, Wong K, Xu Y, Tan L, Chen H, Lu Q, Luo C, Tam C, Zhu L, Su Z, Xie J. Coptisine-induced inhibition of Helicobacter pylori: elucidation of specific mechanisms by probing urease active site and its maturation process. J Enzyme Inhib Med Chem. 2018;33(1):1362-1375. https://doi.org/10.1080/14756366.2018.1501044
  30. Lee IA, Hyun YJ, Kim DH. Berberine ameliorates TNBS-induced colitis by inhibiting lipid peroxidation, enterobacterial growth and NF-κB activation. Eur J Pharmacol. 2010;648(1-3):162-170. https://doi.org/10.1016/j.ejphar.2010.08.046
  31. The European Committee on Antimicrobial Susceptibility Testing. Breakpoint Tables for Interpretation of MICs and Zone Diameters. version 9.0 [Internet]. Vaxjo: The European Committee on Antimicrobial Susceptibility Testing; http://www.eucast.org/clinical_breakpoints. Updated 2019.
  32. Clinical and Laboratory Standards Institute (CLSI). Methods for Antimicrobial Dilution and Disk Susceptibility Testing of Infrequently Isolated or Fastidious Bacteria. 3rd ed. Wayne: CLSI; 2016.
  33. Backert S, Clyne M. Pathogenesis of Helicobacter pylori infection. Helicobacter. 2011;16 Suppl 1:19-25. https://doi.org/10.1111/j.1523-5378.2011.00876.x
  34. Lee KE, Khoi PN, Xia Y, Park JS, Joo YE, Kim KK, Choi SY, Jung YD. Helicobacter pylori and interleukin-8 in gastric cancer. World J Gastroenterol. 2013;19(45):8192-8202. https://doi.org/10.3748/wjg.v19.i45.8192
  35. Siddiqui RA, Akard LP, Garcia JG, Cui Y, English D. Chemotactic migration triggers IL-8 generation in neutrophilic leukocytes. J Immunol. 1999;162(2):1077-1083.
  36. Berg K, Chatterjee A, Yasmin T, Shara M, Bagchi D. Cytokine expression due to Helicobacter pylori in a tissue culture model. Mol Cell Biochem. 2007;300(1-2):171-175. https://doi.org/10.1007/s11010-006-9380-7
  37. Wang YK, Chiang WC, Kuo FC, Wu MC, Shih HY, Wang SSW, Liu CJ, Chen YH, Wu DC, Su WW, Huang YL. Levels of malondialdehyde in the gastric juice: its association with Helicobacter pylori infection and stomach diseases. Helicobacter. 2018;23(2):e12460. https://doi.org/10.1111/hel.12460
  38. Fu S, Ramanujam KS, Wong A, Fantry GT, Drachenberg CB, James SP, Meltzer SJ, Wilson KT. Increased expression and cellular localization of inducible nitric oxide synthase and cyclooxygenase 2 in Helicobacter pylori gastritis. Gastroenterology. 1999;116(6):1319-1329. https://doi.org/10.1016/S0016-5085(99)70496-8
  39. Cho SO, Lim JW, Kim KH, Kim H. Involvement of Ras and AP-1 in Helicobacter pylori-induced expression of COX-2 and iNOS in gastric epithelial AGS cells. Dig Dis Sci. 2010;55(4):988-996. https://doi.org/10.1007/s10620-009-0828-y
  40. Israel DA, Peek RM. Pathogenesis of Helicobacter pylori-induced gastric inflammation. Aliment Pharmacol Ther. 2001;15(9):1271-1290. https://doi.org/10.1046/j.1365-2036.2001.01052.x