Воздействие полисахаридов из морских водорослей на патогенетические мишени Helicobacter pylori - новое направление в терапии и профилактике хеликобактерной инфекции

Согласно эпидемиологическим данным, инфицированность Helicobacter pylori составляет около 60% населения планеты. Применяемое многокомпонентное лечение в 18-20% случаев не позволяет добиться эрадикации H.pylori. Кроме того у большинства пролеченных пациентов через 3-5 лет наступает реинфекция H.pylori. Альтернативой антибиотикам при лечении этой инфекции являются продукты из морских водорослей, в частности экстракты и полисахариды, обладающие антиадгезивными, антитоксическими, иммуномодулирующими, антиоксидантными и противовоспалительными свойствами. Кроме того, полисахариды водорослей оказытают прямое бактерицидное действие и могут разрушать биоплёнки, образованные H.pylori. Представленные в обзоре литературы современные материалы свидетельствуют о перспективности разработок, связанных с использованием экстрактов и полисахаридов из морских водорослей в качестве основы лекарственных препаратов, БАД к пище и продуктов функционального питания для профилактики и лечения хеликобактерной инфекции.

1. Marshall B.J., Warren L.R. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1984; 1 (8390): 1311–1315.

2. Kao C.Y., Chen J.W., Huang Y.T., Sheu S.M., Sheu B.S., Wu J.J. Genome sequence and annotation of Helicobacter pylori strain Hp238, isolated from a Taiwanese patient with mucosa-associated lymphoid tissue lymphoma. Genome Announc 2015; 3 (1): e00006-15.

3. Wang F., Meng W., Wang B., Qiao L. Helicobacter pylori-induced gastric inflammation and gastric cancer. Cancer Lett 2014; 345 (2): 196–202.

4. Menchicchi B., Hensel A., Goycoolea F.M. Polysaccharides as bacterial antiadhesive agents and «smart» constituents for improved drug delivery systems against Helicobacter pylori infection. Curr Pharm Des 2015; 21 (33): 4888–4906.

5. Ярмолик E.C. Роль хеликобактерной инфекции в развитии хронических кожных заболеваний. Журн Гродненского гос мед университета. - 2012. - № 4. - С. 18-22.

6. Ахмедов B.A., Гауе O.B. Внежелудочные проявления, ассоциированные с инфекцией Helicobacter pylori. Клин мед. - 2017. - № 95 (1). - С. 15-22.

7. Cammarota G., Sanguinetti M., Gallo A., Posteraro B. Review article: biofilm formation by Helicobacter pylori as a target for eradication of resistant infection. Aliment Pharmacol Ther 2012; 36 (3): 222–230.

8. Shibata H., Imuro M., Uchiya N., Kawamori T., Nagaoka M., Ueyama S. et al. Preventive effects of Cladosiphon fucoidan against H. pylori infection in Mongolian gerbils. Helicobacter 2003; 8 (1): 59–65.

9. Fitton J.H., Stringer D.N., Park A.Y., Karpiniec S.S. Therapies from fucoidan: new developments. Mar Drugs 2019; 17 (10): 571.

10. Ofec I., Hasty D.L., Sharon N. Anti-adhesion therapy of bacterial diseases: prospects and problems. FEMS Immunol Med Microbiol 2003; 38 (3): 181–191.

11. Menshova R.V., Shevchenko N.M., Imbs T.I., Zvyagintseva T.N., Maluarenko O.S., Zaporoshets T.S. et al. Fucoidans from brown alga Fucus evanescens: structure and biological activity. Front Mar Sci 2016; 3: 129.

12. Delahay R.M., Rugge M. Pathogenesis of Helicobacter pylori infection. Helicobacter 2012; 17: 9–15.

13. Поздеев O.K., Поздеева A.O., Валеева Ю.В., Гуляев П.Е. Механизмы взаимодействия H. pylori с эпителием слизистой оболочки желудка. Факторы патогенности, способствующие успешной колонизации. Инфекция и иммунитет. - 2018. - № 8 (3). - С. 273-283.

14. Clyne M., Dolan B., Reeves E.P. Bacterial factors that mediate colonization of the stomach and virulence of Helicobacter pylori. FEMS Microbiol Lett 2007; 268: 135–143.

15. Иеаева Г. Ш., Валиева Р.И. Биологические свойства и вирулентность Helicobacter pylori. Клин микробиол антимикроб химиотер. - 2018. Т 20. - № 1. - С. 14-23.

16. Koch K.S., Leffert H.L. Hypothesis: Targeted Ikkβ deletion upregulates MIF signaling responsiveness and MHC class II expression in mouse hepatocytes. Hepat Med 2010; 2010 (2): 39–47.

17. Mascellino M.T., Margani M., Oliva A. Helicobacter pylori: determinant and markers of virulence. Dis Markers 2009; 27 (3): 137–156.

18. Успенский Ю.П., Горбачева И.А., Суворов A.H., Галагудза М.М., Барышникова Н.В., Богданова С.А. Иммунологические изменения при инвазии Helicobacter pylori: перспективы создания вакцин. Трансляционная мед. - 2018. - Т. 5. - № 6. - С. 31-40.

19. Ayala G., Cruz-Herrera C.F. Romero I. Exploring alternative treatments for H.pylori infection. World J Gastroenterol 2014; 20 (6): 1450–1469.

20. Kawakubo M., Ito Y., Okimura Y., Kobayashi M., Sakura K., Kasama S. et al. Natural antibiotic function of a human gastric mucin against Helicobacter pylori infection. Science 2004; 305 (5686): 1003–1006.

21. Huang Y., Wang Q.L., Cheng D.D., Xu W.T., Lu N.H. Adhesion and invasion of gastric mucosa epithelial cells by Helicobacter pylori. Front Cell Infect Microbiol 2016; 6: 159.

22. Foegeding N.J, Caston R.R., McClain M.S., Ohi M.D., Cover T.L. An overview of Helicobacter pylori VacA toxin biology. Toxins (Basel) 2016; 8 (6): e173.

23. Terebiznic M.R., Vazquez C.L., Torbick K., Banks D., Wang T., Hong W. et al. Helicobacter pylori VacA toxin promotes bacterial intracellular survival in gastric epithelial cells. Infect. Immun 2006; 74 (12): 6599–6614.

24. Chauhan N., Tay A.C.Y., Marshall B.J., Jain U. Helicobacter pylori VacA, a distinct toxin exert diverse functionalitics in numerous cells: an overview. Helicobacter 2019; 24 (1): e12544.

25. Агеева E.C., Иптышев B.M., Саранчина Ю.В., Штыгашева O.B. Роль апоптоза лимфоцитов крови в дизрегуляции иммунного ответа у пациентов с атрофическнм гастритом. Забайкальский мед вестник. - 2014. - № 3. - С. 94-98.

26. Hathroubi S., Servetas S.L., Windham I., Merrell D.S., Ottemann K.M. Helicobacter pylori formation at its potential role in pathogenesis. Microbiol Mol Biol Rev 2018; 82 (2): e00001-18.

27. Coticchia J.M., Sugawa C., Tran V.R., Gurrola J., Kowalski E., Carron M.A. Presence and density of Helicobacter pylori biofilms in human gastric mucosa in patients with peptic ulcer disease. J Gastrointest Surg 2006; 10 (6): 883–889.

28. Oleastro M., Menard A. The role of Helicobacter pylori outer membrane proteins in adherence and pathogenesis. Biology (Basel) 2013; 2 (3): 1110–1134.

29. Shibata H., Kimura-Takagi I., Nagaoka M., Hashimoto S., Sawada H., Ueyama S. et al. Inhibitory effect of Cladosiphon fucoidan on the adhesion of Helicobacter pylori to human gastric cells. J Nutr Sci Vitaminol 1999; 45 (3): 325–336.

30. Lutau N., Nilsson I., Wadstrom T., Ljungh A. Effect of heparin, fucoidan and other polysaccharides on adhesion of enterohepatic Helicobacter species to murine macrophages. Appl Biochem Biotechnol 2010; 19: 1–18.

31. Chua E.G., Verbrugghe P., Perkins T.T., Tay C.Y. Fucoidans disrupt adherence of H.pylori to AGS cells in vitro. Evid Based Complement Alternat Med 2015; 2015: 120981.

32. Nagaoka M., Shibata H., Takagi I., Aiyama R., Hashimoto S. Effect of fucoidan from Cladosiphon okamuranus (Okinawa Mozuku) on the eradication of Helicobacter pylori. Cell (Tokyo) 2005; 37: 10: 30–33.

33. Loke M.F., Lui S.Y., Ng B.L., Gong M., Ho B. Antiadhesive property of microalgal polysaccharide extract on the binding of Helicobacter pylori to gastric mucin. FEMS Immunol Med Microbiol 2007; 50 (2): 231–238.

34. Krylov V.B., Ustyjuzhanina N.E., Grachev A.A., Nifantiev N.E. Synthesis of large fucoidan fragments, potential inhibitors of microbial adhesion. 4th Baltte Meeting on Microbial Carbohydrates. 2010 Sept 19–22; Hyytiala, Finland. 50.

35. Back H.I., Kim S.Y., Park S.H., Oh M.R., Kim M.G., Jeon J.Y. et al. Effects of fucoidan supplementation on Helicobacter pylori in humans. FASEB J 2010; 24: 1: Suppl Ib 347.

36. Kim T.S., Choi E.K., Kim J., Shin K., Lee S.P., Choi Y. et al. Anti-Helicobacter pylori activities of FEMY-R7 composed of fucoidan and evening primrose extract in mice and humans. Lab Anim Res 2014; 30 (3): 131–135.

37. Kim T.S., Shin K., Jeon J.H., Choi E.K., Choi Y., Lee S.P. et al. Comparative analysis of anti-Helicobacter pylori activities of FEMY-R7 composed of Laminaria japonica and Oenothera biennis extracts in mice and humans. Lab Anim Res 2015; 31 (1): 7–12.

38. Cai J., Kim T.S., Jang J.Y., Kim J., Shin K., Lee S.P. et al. In vitro and in vivo anti-Helicobacter pylori activities of FEMY-R7 composed of fucoidan and evening primrose extract. Lab Anim Res 2014; 30 (1): 28–34.

39. Funatogawa K., Hayashi S., Shimomura H., Yoshida T., Hatano T., Ito H. et al. Antibacterial activity of hydrolyzable tannins derived from medicinal plants against Helicobacter pylori. Microbiol Immunol 2004; 48 (4): 251–261.

40. Решетников О.В., Курилович C.A., Кротов C.A., Белковец Ф.В. Физиологическое и клиническое значение пепсиногенов желудка. Клин мед. - 2014. - № 3. - С. 26-30.

41. Massarrat S., Haj-Sheykholeslami A., Mohamadkhani A., Zendehdel N., Aliasgari A., Rakhshani N. et al. Pepsinogen II can be a potential surrogate marker of morphological changes in corpus before and after H.pylori eradication. Biomed Res Int 2014; 2014: 481607.

42. Choi H.S., Lee S.Y., Kim J.H., Sung I.K., Park H.S., Shim C.S. et al. Combining the serum pepsinogen level and Helicobacter pylori antibody test for predicting the histology of gastric neoplasm. J Dig Dis 2014; 15 (6): 293–298.

43. Fitton J.H., Stringer D.N., Karpiniec S.S. Therapies from fucoidan: an update. Mar Drugs 2015; 13 (9): 5920–5946.

44. Subhash V., Ho B. Inflammation and proliferation — a causal event of host response to Helicobacter pylori infection. Microbiol 2015; 161 (6): 1150–1160.

45. Fitton J.H. Therapies from fucoidans: multifunctional marine polymers. Mar Drugs 2011; 9: 1731–1760.

46. Soares C.M., Malagoli B.G., Menezes G.B., Pinho V.,Souza D.G.,Teixeira M.M. et al. Antiadhesive activity of polysaccharide-rich fractions from Lithothamnion muelleri. Z Naturforsch C J Biosci 2012; 67 (7–8): 391–397.

47. Jin W.,Zhang W., Liang H., Zhang Q. The structure — activity relationship between marine algae polysaccharides and anti-complement activity. Mar Drugs 2016; 14 (1): 3.

48. Manlusoc J.K.T., Hsieh C.L., Hsieh C.Y., Salac E.S.N., Lee Y.T., Tsai P.W. Pharmacologic application potentials of sulfated polysaccharide from marine algae. Polymers 2019; 11: 1163–1184.

49. Park H.Y., Han M.H., Park C., Jin C.Y., Kim G.Y., Choi I.W. et al. Anti-inflammatory effects of fucoidan through inhibition of NF-κB, MAPK and Akt activation in lipopolysaccharide-induced BV2 microglia cells. Food Chem Toxicol 2011; 49: 1745–1752.

50. Wu G.J., Shiu S.M., Hsieh M.C., Tsai G.J. Anti-inflammatory activity of a sulfated polysaccharide from the brown alga Sargassum cristaefolium. Food Hydrocoll 2016; 53: 16–23.

51. Sanjeeva K.K.A., Fernando I.P.S., Kim S.Y., Kim W. S., Ahn G., Jee Y. et al. Ecklonia cava (Laminariales) and Sargassum horneri (Fucales) synergistically inhibit the lipopolysaccharide-induced inflammation via blocking NF-kB and MAPK pathways. Algae 2019; 34 (1): 45–56.

52. Saraswaty, Giriwono P.E., Iskandriati D.,Tan C.P., Andarwulan N. Sargassum seaweed as a source of anti-inflammatory substances and the potential insight of the tropical species: a review. Mar. Drugs 2019; 17 (10): 590.

53. Matsumoto S., Nagaoka M., Hara T., Kimura-Takagi I., Mistuyama K., Ueyama S. Fucoidan derived from Cladosiphon okamuranus Tokida ameliorates murine chronic colitis through down-regulation of interleukin-6 production on colonic epithelial cells. Clin Exp Immunol 2004; 136 (3): 432–439.

54. Никитина Л.В. Коррекция иммунных нарушений у детей с хроническим гастродуоденитом, ассоциированным с Helicobacter pylori. : автореф. днс. канд. мед. наук: Курск, 2012. - 18 с.

55. Kuznetsova T.A., Besednova N.N., Somova L.M., Plekhova N.G. Fucoidan Extracted from Fucus evanescens Prevents Endotoxin-Induced Damage in a Mouse Model of Endotoxemia. Mar Drugs 2014; 12 (2): 886–898.

56. Butcher L.D., den Hartog G., Ernst P.B., Crowe S.E. Oxidative stress resulting from Helicobacter pylori infection contributes to gastric carcinogenesis. Cell Mol Gastroenterol Hepatol 2017; 3 (3): 316–322.

57. Байдик О.Д., Титаренко M.A., Сысолятин П.Г. Роль оксида азота (11) и его активных метаболитов в канцерогенезе полости рта. Российский стоматол журн. - 2016. - Т. 20. - № 3. - С. 165-168.

58. Ajisaka K., Yokoyama T., Matsuo K. Structural Characteristics and antioxidant activities from five brown seaweed. J of Applied Glycoscience 2016; 63 (2): 31–37.

59. Xu S-Y., Huang X., Cheong K-L. Recent advances in marine algae polysaccharides: isolation, structure and activities. Mar Drugs 2017; 15 (12): 388.

60. Tomori M., Nagamine T., Miyamoto T., Iha M. Evaluation of the immunomodulatory effects of fucoidan derived from Cladosiphon okamuranus Tokida in mice. Mar Drugs 2019; 17 (10): 547.

61. Asker M.S., El Kady E.M., Mahmoud M.G. New trends of the Polysaccharides as a drug. World J Agri Soil Sci 2019; 3 (4): 1–22.

62. Lin Y.H., Lu K.Y., Tseng C.L., Wu J.Y., Chen C.H., Mi F.L. Development of genipin-crosslinked fucoidan/chitosan-N-arginine nanogels for preventing Helicobacter infection. Nanomedicine 2017; 12 (12): 1491-510.

63. Gutiérrez-Zamorano C., González-Ávila M., Díaz-Blas G., Smith C.T., González-Correa C., García-Cancino A. Increased anti-Helicobacter pylori effect of the probiotic Lactobacillus fermentum UCO-979C strain encapsulated in gastric simulations under fasting conditions. Food Res Int 2019; 121: 812-816.

64. Pandey S., Kalvadia P., Patel H., Shah R., Gupta A., Shah D. Mucoadhesive microcapsules of amoxicillin trihydrate for effective treatment of H.pylori. Der Pharmacia Sinica 2014; 5 (2): 45–-55.

65. Arora S., Gupta S., Narang R.K., Budhiraja R.D. Amoxicillin loaded chitosan-alginate polyelectrolyte complex nanoparticles as mucopenetrating delivery system for H.pylori. Sci Pharm. 2011; 79 (3): 673–694.

66. Adebisi A.O.,Conway B.R. Preparation and characterization of gastroretentive alginate beads for targeting H. pylori. J Microencapsul 2014; 31 (1): 58–67.

67. Аминина Н.М. Биологическая ценность морских водорослей дальневосточного побережья. Рыбпром: технологии и оборудование для переработки водных биоресурсов. - 2010. - № 3. - С. 32-35.

68. Abadi A.T.B. Vaccine against Helicobacter pylori: invitable approach. World J Gastroenterol 2016; 22 (11): 3150–3157.

69. Pan X., Ke H., Niu X., Li S., Lv J., Pan L. Protection against Helicobacter pylori infection in Balb/c mouse model by oral administration of multi- valent epitope-based vaccine of cholera toxin B subunit-HUUC. Front Immunol 2018; 9: 1003.

70. Kuznetsova T.A., Persiyanova E.V., Ermakova S.P., Khotimchenko M.Y., Besednova N.N. The Sulfated Polysaccharides of Brown Algae and Products of Their Enzymatic Transformation as Potential Vaccine Adjuvants. Nat Prod Commun 2018; 13 (8): 1083–1095.

71. Richter M.F., Hergenrother P.J. The challenge of converting Gram-positive-only compounds into broad-spectrum antibiotics. Ann N Y Acad Sci 2019; 1435 (1): 18–38.

72. Willyard C. The drug-resistant bacteria that pose the greatest health threats. Nature 2017; 543 (7643): 15.