Противовоспалительные эффекты оливкового масла и его компонентов. Перспективы применения в лечении воспалительных заболеваний кишечника

В последние годы отмечается значительный рост распространенности воспалительных заболеваний кишечника. Несмотря на значительный прогресс, достигнутый в инструментальной диагностике данной группы заболеваний, их лечение в большинстве случаев остается формализованным, основанным на достаточно жестких схемах. В этом контексте актуальным направлением современных исследований является изучение эффективности использования диетотерапии и определенных продуктов питания в целях модуляции активности воспалительного процесса, позволяющей избежать побочных реакций иммуносупрессивной, в том числе и иммунобиологической, терапии. Соблюдение средиземноморской диеты доказало свою эффективность в терапии хронической неинфекционной патологии. Недавние исследования также установили ее преимущества в лечении воспалительных заболеваний кишечника. Одной из составляющих средиземноморской диеты является оливковое масло. В данной статье будут представлены результаты современных исследований, посвященных влиянию употребления оливкового масла и его соединений на течение воспалительных процессов в кишечнике. Ряд исследований, проведенных in vitro и на животных моделях, выявил механизмы, с помощью которых оливковое масло и его компоненты оказывают положительное влияние на течение воспаления в кишечной стенке посредством противовоспалительного, антиоксидантного, иммуномодулирующего и противоопухолевого действия. Немногочисленные клинические исследования, проведенные на пациентах с воспалительными заболеваниями кишечника, показали возможность использования диетотерапии с добавлением оливкового масла у данной группы пациентов в качестве дополнительного лечения.

1. Хавкин А.И., Налетов А.В., Марченко Н.А. Воспалительные заболевания кишечника у детей: современные достижения в диагностике и терапии // Российский журнал гастроэнтерологии, гепатологии, колопроктологии. — 2023. — Т. 33. — № 6. — С. 7–15. — https://doi.org/10.22416/1382-4376-2023-33-6-7-15

2. Хавкин А.И., Налетов А.В., Федулова Э.Н., Марченко Н.А. Воспалительные заболевания кишечника у детей: алгоритмы диагностики и современные стратегии терапии // Вопросы диетологии. — 2023. — Т. 13. — № 3. — С. 32–43. — https://doi.org/10.20953/2224-5448-2023-3-32-42

3. Хавкин А.И., Налетов А.В., Марченко Н.А. Кишечная микробиота и микроРНК при воспалительных заболеваниях кишечника // Вопросы диетологии. — 2023. — Т. 13. — № 4. — С. 55–63. — https://doi.org/10.20953/2224-5448-2023-4-55-63

4. Хавкин А.И., Налетов А.В., Шумилов П.В. и др. Диетические аспекты лечения воспалительных заболеваний кишечника // Вопросы детской диетологии. — 2024. — Т. 22. — № 1. — С. 51–62. — https://doi.org/10.20953/1727-5784-2024-1-51-62

5. Cox SR, Lindsay JO, Fromentin S, et al. Effects of Low-FODMAP diet on symptoms, fecal microbiome, and markers of inflammation in patients with quiescent inflammatory bowel disease in a randomized trial. Gastroenterology. 2020;158(1):176–188.e7. https://doi.org/10.1053/j.gastro.2019.09.024

6. Bodini G, Zanella C, Crespi M, et al. A randomized, 6-wk trial of a low FODMAP diet in patients with inflammatory bowel disease. Nutrition. 2019;67-68:110542. https://doi.org/10.1016/j.nut.2019.06.023

7. Schreiner P, Yilmaz B, Rossel JB, et al. Vegetarian or gluten-free diets in patients with inflammatory bowel disease are associated with lower psychological well-being and a different gut microbiota, but no beneficial effects on the course of the disease. United Eur Gastroenterol J. 2019;7(6):767–781. https://doi.org/10.1177/2050640619841249

8. Chicco F, Magrì S, Cingolani A, et al. Multidimensional impact of Mediterranean diet on IBD patients. Inflamm Bowel Dis.2021;27(1):1–9. https://doi.org/10.1093/ibd/izaa097

9. Papada E, Amerikanou C, Forbes A, Kaliora AC. Adherence to Mediterranean diet in Crohn’s disease. Eur J Nutr. 2020;59(3):1115–1121. https://doi.org/10.1007/s00394-019-01972-z

10. Tosti V, Bertozzi B, Fontana L. Health benefits of the Mediterranean Diet: metabolic and molecular mechanisms. J Gerontol A Biol Sci Med Sci. 2018;73(3):318–326. https://doi.org/10.1093/gerona/glx227

11. Mattioli AV, Palmiero P, Manfrini O, et al. Mediterranean diet impact on cardiovascular diseases: A narrative review. J Cardiovasc Med (Hagerstown). 2017;18(12):925–935. https://doi.org/10.2459/JCM.0000000000000573

12. De Santis S, Cariello M, Piccinin E, et al. Extra virgin olive oil: lesson from nutrigenomics. Nutrients. 2019;11(9):2085. https://doi.org/10.3390/nu11092085

13. Blekas G, Tsimidou M, Boskou D. Olive oil composition. In: Olive Oil. Urbana, IL, USA: AOCS Press; 2006.

14. Corona G, Tzounis X, Dessì MA, et al. The fate of olive oil polyphenols inthe gastrointestinal tract: Implications of gastric and colonic microflora-dependent biotransformation. Free Radic Res. 2006;40(6):647–658. https://doi.org/10.1080/10715760500373000

15. Menicacci B, Cipriani C, Margheri F, et al. Modulation of the senescence-associated inflammatory phenotype in human fibroblasts by olive phenols. Int J Mol Sci. 2017;18(11):2275. https://doi.org/10.3390/ijms18112275

16. Karković Marković A, Torić J, Barbarić M, Jakobušić Brala C. Hydroxytyrosol, tyrosol and derivatives and their potential effects on human health. Molecules. 2019;24(10):2001. https://doi.org/10.3390/molecules24102001

17. Deiana M, Serra G, Corona G. Modulation of intestinal epithelium homeostasis by extra virgin olive oil phenolic compounds. Food Funct. 2018;9(8):4085–4099. https://doi.org/10.1039/c8fo00354h

18. Шрайнер Е.В., Хавкин А.И., Новикова М.С. и др. Современные стратегии и перспективы лечения язвенного колита // Экспериментальная и клиническая гастроэнтерология. — 2023. — № 1. — С. 149–157. — https://doi.org/10.31146/1682-8658-ecg-209-1-149-157

19. Яблокова Е.А., Джабарова А.К., Лохматов М.М. и др. Внекишечные проявления воспалительных заболеваний кишечника у детей // Экспериментальная и клиническая гастроэнтерология. — 2023. — № 1. — С. 165–177. — https://doi.org/10.31146/1682-8658-ecg-209-1-165-177

20. Cardeno A, Sanchez-Hidalgo M, Aparicio-Soto M, Alarcón-De-La-Lastra C. Unsaponifiable fraction from extra virgin olive oil inhibits the inflammatory response in LPS-activated murine macrophages. Food Chem. 2014;147:117–123. https://doi.org/10.1016/j.foodchem.2013.09.117

21. Cárdeno A, Magnusson M, Strid H, et al. The unsaponifiable fraction of extra virgin olive oil promotes apoptosis and attenuates activation and homing properties of T cells from patients with inflammatory bowel disease. Food Chem. 2014;161:353–360. https://doi.org/10.1016/j.foodchem.2014.04.016

22. Serra G, Incani A, Serreli G, et al. Olive oil polyphenols reduce oxysterols-induced redox imbalance and pro-inflammatory response in intestinal cells. Redox Biol. 2018;17:348–354. https://doi.org/10.1016/j.redox.2018.05.006

23. Serra G, Deiana M, Spencer JPE, Corona G. Olive oil phenolics prevent oxysterol-induced proinflammatory cytokine secretion and reactive oxygen species production in human peripheral blood mononuclear cells, through modulation of p38 and JNK pathways. Mol Nutr Food Res. 2017;61(12):1700283. https://doi.org/10.1002/mnfr.201700283

24. Chiesi C, Fernandez-Blanco C, Cossignani L, et al. Alternariolinduced cytotoxicity in Caco-2 cells. Protective effect of the phenolic fraction from virgin olive oil. Toxicon. 2015;93:103–111. https://doi.org/10.1016/j.toxicon.2014.11.230

25. Muto E, Dell’Agli M, Sangiovanni E, et al. Olive oil phenolic extract regulates interleukin-8 expression by transcriptional and posttranscriptional mechanisms in Caco-2 cells. Mol Nutr Food Res. 2015;59(6):1217–1221. https://doi.org/10.1002/mnfr.201400800

26. Serreli G, Melis MP, Corona G, Deiana M. Modulation of LPSinduced nitric oxide production in intestinal cells by hydroxytyrosol and tyrosol metabolites: Insight into the mechanism of action. Food Chem Toxicol. 2019;125:520–527. https://doi.org/10.1016/j.fct.2019.01.039

27. Di Nunzio M, Picone G, Pasini F, et al. Olive oil industry by-products. Effects of a polyphenol-rich extract on the metabolome and response to inflammation in cultured intestinal cell. Food Res Int. 2018;113:392–400. https://doi.org/10.1016/j.foodres.2018.07.025

28. Borges TH, Cabrera-Vique C, Seiquer I. Antioxidant properties of chemical extracts and bioaccessible fractions obtained from six Spanish monovarietal extra virgin olive oils: Assays in Caco-2 cells. Food Funct. 2015;6(7):2375–2383. https://doi.org/10.1039/c5fo00529a

29. Guina T, Deiana M, Calfapietra S, et al. The role of p38 MAPK in the induction of intestinal inflammation by dietary oxysterols: Modulation by wine phenolics. Food Funct. 2015;6(4):1218–1228. https://doi.org/10.1039/c4fo01116c

30. Mateos R, Caro GP, Bacon JR, et al. Anticancer activity of olive oil hydroxytyrosyl acetate in human adenocarcinoma Caco-2 cells. J Agric Food Chem. 2013;61(13):3264–3269. https://doi.org/10.1021/jf305158q

31. Lopez de las Hazas MC, Piñol C, Macià A, Motilva MJ. Hydroxytyrosol and the colonic metabolites derived from virgin olive oil intake induce cell cycle arrest and apoptosis in colon cancer cells. J Agric Food Chem. 2017;65(31):6467–6476. https://doi.org/10.1021/acs.jafc.6b04933

32. LaRussa T, Oliverio M, Suraci E, et al. Oleuropein Decreases Cyclooxygenase-2 and Interleukin-17 Expression and Attenuates Inflammatory Damage in Colonic Samples from Ulcerative Colitis Patients. Nutrients. 2017;9(4):391. https://doi.org/10.3390/nu9040391

33. Vezza T, Algieri F, Rodríguez-Nogales A, et al. Immunomodulatory properties of Olea europaea leaf extract in intestinal inflammation. Mol Nutr Food Res. 2017;61(10):1601066. https://doi.org/10.1002/mnfr.201601066

34. Kondreddy VKR, Naidu KA. Oleic acid, hydroxytyrosol and n-3 fatty acids collectively modulate colitis through reduction of oxidative stress and IL-8 synthesis; in vitro and in vivo studies. Int Immunopharmacol. 2016;35:29–42. https://doi.org/10.1016/j.intimp.2016.03.019

35. Sánchez-Fidalgo S, Sánchez De Ibargüen L, Cárdeno A, Alarcon De La Lastra C. Influence of extra virgin olive oil diet enriched with hydroxytyrosol in a chronic DSS colitis model. Eur J Nutr. 2011;51(4):497–506. https://doi.org/10.1007/s00394-011-0235-y

36. Sánchez-Fidalgo S, Cárdeno A, Hidalgo MS, et al. Dietary extra virgin olive oil polyphenols supplementation modulates DSS-induced chronic colitis in mice. J Nutr Biochem. 2013;24(7):1401–1413. https://doi.org/10.1016/j.jnutbio.2012.11.008

37. Sánchez-Fidalgo S, Cárdeno A, Hidalgo MS, et al. Dietary unsapon-ifiable fraction from extra virgin olive oil supplementation attenuates acute ulcerative colitis in mice. Eur J Pharm Sci. 2013;48(3):572–581. https://doi.org/10.1016/j.ejps.2012.12.004

38. Takashima T, Sakata Y, Iwakiri R, et al. Feeding with olive oil attenuates inflammation in dextran sulfate sodium-induced colitis in rat. J Nutr Biochem. 2014;25(2):186–192. https://doi.org/10.1016/j.jnutbio.2013.10.005

39. Cariello M, Contursi A, Gadaleta RM, et al. Extra-virgin olive oil from Apulian Cultivars and intestinal inflammation. Nutrients. 2020;12(4):1084. https://doi.org/10.3390/nu12041084

40. Huguet-Casquero A, Xu Y, Gainza E, et al. Oral delivery of oleuropein-loaded lipid nanocarriers alleviates inflammation and oxidative stress in acute colitis. Int J Pharm. 2020;586:119515. https://doi.org/10.1016/j.ijpharm.2020.119515

41. Voltes A, Bermúdez A, Rodríguez-Gutiérrez G, et al. AntiInflammatory local effect of hydroxytyrosol combined with pectinalginate and olive oil on trinitrobenzene sulfonic acidinduced colitis in wistar rats. J Investig Surg. 2020;33(1):8–14. https://doi.org/10.1080/08941939.2018.1469697

42. Marcelino G, Hiane PA, Freitas KDC, et al. Effects of olive oil and its minor components on cardiovascular diseases, inflammation, and gut microbiota. Nutrients. 2019;11(8):1826. https://doi.org/10.3390/nu11081826

43. Skrypnik K, Bogdański P., Łoniewski I. et al. Effect of probiotic supplementation on liver function and lipid status in rats. Acta Sci Pol Technol Aliment. 2015;17(2):185–192. https://doi.org/10.17306/J.AFS.0554

44. Liu Z, Wang N, Ma Y, Wen D. Hydroxytyrosol improves obesity and insulin resistance by modulating gut microbiota in high-fat dietinduced obese mice. Front Microbiol. 2019;10:390. https://doi.org/10.3389/fmicb.2019.00390

45. Millman J, Okamoto S, Kimura A, et al. Metabolically and immunologically beneficial impact of extra virgin olive and flaxseed oils on composition of gut microbiota in mice. Eur J Nutr. 2020;59(6):2411–2425. https://doi.org/10.1007/s00394-019-02088-0

46. Farràs M, Martinez-Gili L, Portune K, et al. Modulation of the gut microbiota by olive oil phenolic compounds: implications for lipid metabolism, immune system, and obesity. Nutrients. 2020;12(8):2200. https://doi.org/10.3390/nu12082200

47. do Nascimento RDP, Lima AV, Oyama LM, et al. Extra virgin olive oil and flaxseed oil have no preventive effects on DSS-induced acute ulcerative colitis. Nutrients. 2020;74:110731. https://doi.org/10.1016/j.nut.2020.110731

48. Bigagli E, Toti S, Lodovici M, et al. Dietary extra-virgin olive oil polyphenols do not attenuate colon inflammation in transgenic HLAB-27 rats but exert hypocholesterolemic effects through the modulation of HMGCR and PPAR-α gene expression in the liver. Lifestyle Genom. 2018;11(2):99–108. https://doi.org/10.1159/000495516

49. Daniel K, Vitetta L, Singh MAF. Effects of olives and their constituents on the expression of ulcerative colitis: A systematic review of randomised controlled trials. Br J Nutr. 2021;127(8):1153–1171. https://doi.org/10.1017/S0007114521001999

50. De Filippis F, Pellegrini N, Vannini L, et al. High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome. Gut. 2016;65(11):1812–1821. https://doi.org/10.1136/gutjnl-2015-309957

51. Godny L, Reshef L, Pfeffer-Gik T, et al. Adherence to the Mediterranean diet is associated with decreased fecal calprotectin in patients with ulcerative colitis after pouch surgery. Eur J Nutr. 2020;59(7):3183–3190. https://doi.org/10.1007/s00394-019-02158-3

52. Vrdoljak J, Vilović M, Živković PM, et al. Mediterranean diet adherence and dietary attitudes in patients with inflammatory bowel disease. Nutrients. 2020;12(11):3429. https://doi.org/10.3390/nu12113429

53. Morvaridi M, Jafarirad S, Seyedian SS, et al. The effects of extra virgin olive oil and canola oil on inflammatory markers and gastrointestinal symptoms in patients with ulcerative colitis. Eur J Clin Nutr. 2020;74(6):891–899. https://doi.org/10.1038/s41430-019-0549-z

54. Martín-Peláez S, Mosele JI, Pizarro N, et al. Effect of virgin olive oil and thyme phenolic compounds on blood lipid profile: Implications of human gut microbiota. Eur J Nutr. 2015;56(1):119–131. https://doi.org/10.1007/s00394-015-1063-2

55. de Silva PS, Luben R, Shrestha SS, et al. Dietary arachidonic and oleic acid intake in ulcerative colitis etiology: A prospective cohort study using 7-day food diaries. Eur J Gastroenterol Hepatol. 2014;26(1):11–18. https://doi.org/10.1097/MEG.0b013e328365c372