ISSN 2412-4036 (print)
ISSN 2713-1823 (online)

Плейотропные эффекты гимекромона в терапии хронических заболеваний печени и билиарного тракта

Е.Ю. Плотникова, Л.Г. Вологжанина, С.Р. Дружинина, М.А. Синьков, Ю.В. Котелевцев

1) ФГБОУ ВО «Кемеровский государственный медицинский университет» Минздрава России, г. Кемерово, Российская Федерация; 2) ФГБОУ ВО «Пермский государственный медицинский университет имени академика Е.А. Вагнера» Минздрава России, г. Пермь, Российская Федерация; 3) ООО «ГАСТРОЦЕНТР» г. Пермь, Российская Федерация; 4) ФГБНУ «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний», г. Кемерово, Российская Федерация; 5) Центр био- и медицинских технологий, Сколковский институт науки и технологий (Сколтех), г. Москва, Российская Федерация
Аннотация. Фиброз печени является распространенным конечным результатом хронического повреждения гепатоцитов. Клинический прогресс в разработке препаратов против фиброза печени набирает обороты: к ним относятся различные лекарственных средств, включая гимекромон (4-MU). Цель – оценить противовоспалительную и антифибротическую эффективность гимекромона у пациентов с сочетанной патологией билиарного тракта и печени. Материалы и методы. В исследовании приняли участие 55 пациентов (31 женщина и 24 мужчины) 18–75 лет с хроническими гепатитами различной этиологии и фиброзом печени (F 1–4) в сочетании с билиарной патологией. Исследование закончили 20 пациентов. Всем участникам назначался гимекромон по 200 мг 3 раза/сут. в течение 3 нед. с последующим перерывом в 1 нед., курс повторялся в течение 6 мес. Также все пациенты получали урсодезоксихолевую кислоту в дозе 10 мг/кг массы тела на ночь постоянно на протяжении 6 мес. Результаты. Все пациенты на фоне проводившейся терапии отмечали улучшение самочувствия, повышение физической активности и работоспособности. Также у них отмечались статистически значимое снижение уровня биохимических маркеров (р = 0,001–0,049) и положительные статистически значимые изменения показателей фиброэластометрии (p <0,001) через 6 мес. наблюдения. Заключение. Назначенная нами схема лечения продемонстрировала выраженную антифибротическую эффективность (р = 0,001), а также сопровождалась статистически значимым снижением печеночных маркеров. Необходимо продолжать исследования по применению гимекромона (4-MU) при хронических заболеваниях печени.

Ключевые слова

хронический гепатит
фиброз печени
патология билиарного тракта
синдром цитолиза
гимекромон
плейотропные эффекты гимекромона

Список литературы

1. Lambrecht J, van Grunsven LA, Tacke F. Current and emerging pharmacotherapeutic interventions for the treatment of liver fibrosis. Expert Opin Pharmacother. 2020;21(13):1637–50.

PMID: 32543284. https://doi.org/10.1080/14656566.2020.1774553

2. Roehlen N, Crouchet E, Baumert TF. Liver fibrosis: mechanistic concepts and therapeutic perspectives. Cells. 2020;9(4):875.

PMID: 32260126. PMCID: PMC7226751. https://doi.org/10.3390/cells9040875

3. Zhao J, Qi YF, Yu YR. STAT3: A key regulator in liver fibrosis. Ann Hepatol. 2021;21:100224.

PMID: 32702499. https://doi.org/10.1016/j.aohep.2020.06.010

4. Chen S, Wu Z, Zhang J, Lin Y, Xie J, Yin D, Zhu Y. Research and application of medicines for treating liver fibrosis: Current status and prospects. Front Pharmacol. 2025;16:1582258.

PMID: 40703362. PMCID: PMC12283635. https://doi.org/10.3389/fphar.2025.1582258

5. Jeon S, Carr R. Alcohol effects on hepatic lipid metabolism. J Lipid Res. 2020;61(4):470–79.

PMID: 32029510. PMCID: PMC7112138. https://doi.org/10.1194/jlr.R119000547

6. Odenwald MA, Paul S. Viral hepatitis: Past, present, and future. World J Gastroenterol. 2022;28(14):1405–29.

PMID: 35582678. PMCID: PMC9048475. https://doi.org/10.3748/wjg.v28.i14.1405

7. Pouwels S, Sakran N, Graham Y, Leal A, Pintar T, Yang W et al. Non-alcoholic fatty liver disease (NAFLD): A review of pathophysiology, clinical management and effects of weight loss. BMC Endocr Disord. 2022;22(1):63.

PMID: 35287643. PMCID: PMC8919523. https://doi.org/10.1186/s12902-022-00980-1

8. Ahmed A, Wong RJ, Harrison SA. Nonalcoholic fatty liver disease review: Diagnosis, treatment, and outcomes. Clin Gastroenterol Hepatol. 2015;13(12):2062–70.

PMID: 26226097. https://doi.org/10.1016/j.cgh.2015.07.029

9. Bandmann O, Weiss KH, Kaler SG. Wilson’s disease and other neurological copper disorders. Lancet Neurol. 2015;14(1):103–13.

PMID: 25496901. PMCID: PMC4336199. https://doi.org/10.1016/S1474-4422(14)70190-5

10. Kane SF, Roberts C, Paulus R. Hereditary hemochromatosis: Rapid evidence review. Am Fam Physician. 2021;104(3):263–70. PMID: 34523883.

11. Carbone M, Neuberger JM. Autoimmune liver disease, autoimmunity and liver transplantation. J Hepatol. 2014;60(1):210–23.

PMID: 24084655. https://doi.org/10.1016/j.jhep.2013.09.020

12. Sanyal AJ, Castera L, Wong VW. Noninvasive assessment of liver fibrosis in NAFLD. Clin Gastroenterol Hepatol. 2023;21(8):2026–39.

PMID: 37062495. https://doi.org/10.1016/j.cgh.2023.03.042

13. Kaplan DE, Teerlink CC, Schwantes-An TH, Norden-Krichmar TM, DuVall SL, Morgan TR et al. Clinical and genetic risk factors for progressive fibrosis in metabolic dysfunction-associated steatotic liver disease. Hepatol Commun. 2024;8(7):e0487.

PMID: 38967582. PMCID: PMC11227360. https://doi.org/10.1097/HC9.0000000000000487

14. Ericson E, Bergenholm L, Andreasson AC, Dix CI, Knochel J, Hansson SF et al. Hepatic patatin-like phospholipase domain-containing 3 levels are increased in I148M risk allele carriers and correlate with NAFLD in humans. Hepatol Commun. 2022;6(10):2689–701.

PMID: 35833455. PMCID: PMC9512469. https://doi.org/10.1002/hep4.2032

15. Liu J, Ginsberg HN, Reyes-Soffer G. Basic and translational evidence supporting the role of TM6SF2 in VLDL metabolism. Curr Opin Lipidol. 2024;35(3):157–61.

PMID: 38465912. PMCID: PMC11168781. https://doi.org/10.1097/MOL.0000000000000930

16. Fabbrini E, Rady B, Koshkina A, Jeon JY, Ayyar VS, Gargano C et al. Phase 1 trials of PNPLA3 siRNA in I148M homozygous patients with MAFLD. N Engl J Med. 2024;391(5):475–76.

PMID: 39083780. https://doi.org/10.1056/NEJMc2402341

17. Moran-Salvador E, Mann J. Epigenetics and liver fibrosis. Cell Mol Gastroenterol Hepatol. 2017;4(1):125–34.

PMID: 28593184. PMCID: PMC5453904. https://doi.org/10.1016/j.jcmgh.2017.04.007

18. Barchetta I, Zampieri M, Cimini FA, Dule S, Sentinelli F, Passarella G et al. Association between active DNA demethylation and liver fibrosis in individuals with metabolic-associated steatotic liver disease (MASLD). Int J Mol Sci. 2025;26(3):1271.

PMID: 39941038. PMCID: PMC11818491. https://doi.org/10.3390/ijms26031271

19. Akkız H, Gieseler RK, Canbay A. Liver fibrosis: From basic science towards clinical progress, focusing on the central role of hepatic stellate cells. Int J Mol Sci. 2024;25(14):7873.

PMID: 39063116. PMCID: PMC11277292. https://doi.org/10.3390/ijms25147873

20. Liu Y, Wen D, Ho C, Yu L, Zheng D, O’Reilly S et al. Epigenetics as a versatile regulator of fibrosis. J Transl Med. 2023;21(1):164.

PMID: 36864460. PMCID: PMC9983257. https://doi.org/10.1186/s12967-023-04018-5

21. Li H, Liu T, Yang Y, Cho WC, Flynn RJ, Harandi MF et al. Interplays of liver fibrosis-associated microRNAs: Molecular mechanisms and implications in diagnosis and therapy. Genes Dis. 2022;10(4):1457–69.

PMID: 37397560. PMCID: PMC10311052. https://doi.org/10.1016/j.gendis.2022.08.013

22. Rodimova S, Mikhailova L, Arabuli K, Kozlov D, Kozlova V, Kuzmin D et al. MicroRNA-200a as a therapeutic agent for acute and chronic liver pathologies and regeneration. Biomaterials. 2026;331:124125.

PMID: 41855855. https://doi.org/10.1016/j.biomaterials.2026.124125

23. Schwabe RF, Luedde T. Apoptosis and necroptosis in the liver: a matter of life and death. Nat Rev Gastroenterol Hepatol. 2018;15(12):738–52.

PMID: 30250076. PMCID: PMC6490680. https://doi.org/10.1038/s41575-018-0065-y

24. Woolbright BL, Jaeschke H. Role of the inflammasome in acetaminophen-induced liver injury and acute liver failure. J Hepatol. 2017;66(4):836–48.

PMID: 27913221. PMCID: PMC5362341. https://doi.org/10.1016/j.jhep.2016.11.017

25. Chen M, Zhong W, Xu W. Alcohol and the mechanisms of liver disease. J Gastroenterol Hepatol. 2023;38(8):1233–40.

PMID: 37423758. https://doi.org/10.1111/jgh.16282

26. Banerjee A, Farci P. Fibrosis and hepatocarcinogenesis: Role of gene-environment interactions in liver disease progression. Int J Mol Sci. 2024;25(16):8641.

PMID: 39201329. PMCID: PMC11354981. https://doi.org/10.3390/ijms25168641

27. Paradies G, Paradies V, Ruggiero FM, Petrosillo G. Oxidative stress, cardiolipin and mitochondrial dysfunction in nonalcoholic fatty liver disease. World J Gastroenterol. 2014;20(39):14205–18.

PMID: 25339807. PMCID: PMC4202349. https://doi.org/10.3748/wjg.v20.i39.14205

28. Zheng H, Sechi LA, Navarese EP, Casu G, Vidili G. Metabolic dysfunction-associated steatotic liver disease and cardiovascular risk: A comprehensive review. Cardiovasc Diabetol. 2024;23(1):346.

PMID: 39342178. PMCID: PMC11439309. https://doi.org/10.1186/s12933-024-02434-5

29. Zhao YQ, Deng XW, Xu GQ, Lin J, Lu HZ, Chen J. Mechanical homeostasis imbalance in hepatic stellate cells activation and hepatic fibrosis. Front Mol Biosci. 2023;10:1183808.

PMID: 37152902. PMCID: PMC10157180. https://doi.org/10.3389/fmolb.2023.1183808

30. Yang AT, Kim YO, Yan XZ, Abe H, Aslam M, Park KS et al. Fibroblast activation protein activates macrophages and promotes parenchymal liver inflammation and fibrosis. Cell Mol Gastroenterol Hepatol. 2023;15(4):841–67.

PMID: 36521660. PMCID: PMC9972574. https://doi.org/10.1016/j.jcmgh.2022.12.005

31. Liu X, Liu D, Tan C, Feng W. Gut microbiome-based machine learning for diagnostic prediction of liver fibrosis and cirrhosis: A systematic review and meta-analysis. BMC Med Inform Decis Mak. 2023;23(1):294.

PMID: 38115019. PMCID: PMC10731850. https://doi.org/10.1186/s12911-023-02402-1

32. Fuchs CD, Simbrunner B, Baumgartner M, Campbell C, Reiberger T, Trauner M. Bile acid metabolism and signalling in liver disease. J Hepatol. 2025;82(1):134–53.

PMID: 39349254. https://doi.org/10.1016/j.jhep.2024.09.032

33. Tang YL, Zhu L, Tao Y, Lu W, Cheng H. Role of targeting TLR4 signaling axis in liver-related diseases. Pathol Res Pract. 2023;244:154410.

PMID: 36917917. https://doi.org/10.1016/j.prp.2023.154410

34. Wang XX, Xie C, Libby AE, Ranjit S, Levi J, Myakala K et al. The role of FXR and TGR5 in reversing and preventing progression of Western diet-induced hepatic steatosis, inflammation, and fibrosis in mice. J Biol Chem. 2022;298(11):102530.

PMID: 36209823. PMCID: PMC9638804. https://doi.org/10.1016/j.jbc.2022.102530

35. Hizo GH, Rampelotto PH. The impact of probiotic Bifidobacterium on liver diseases and the microbiota. Life (Basel). 2024;14(2):239.

PMID: 38398748. PMCID: PMC10890151. https://doi.org/10.3390/life14020239

36. Gleeson J, Barry J, O’Reilly S. Use of liver imaging and biopsy in clinical practice. N Engl J Med. 2017;377(23):2296.

PMID: 29215220. https://doi.org/10.1056/NEJMc1712445

37. Wendum D, Lacombe K, Chevallier M, Callard P, Valet F, Miailhes P et al. Histological scoring of fibrosis and activity in HIV-chronic hepatitis B related liver disease: Performance of the METAVIR score assessed on virtual slides. J Clin Pathol. 2009;62(4):361–63.

PMID: 19126564. https://doi.org/10.1136/jcp.2008.062349

38. Scott DR, Levy MT. Liver transient elastography (Fibroscan): A place in the management algorithms of chronic viral hepatitis. Antivir Ther. 2010;15(1):1–11.

PMID: 20167986. https://doi.org/10.3851/IMP1474

39. Xu X, Jin J, Liu Y. Performance of FibroScan in grading steatosis and fibrosis in patients with nonalcoholic fatty liver disease: A meta-analysis. Arab J Gastroenterol. 2023;24(4):189–97.

PMID: 37996351. https://doi.org/10.1016/j.ajg.2023.08.003

40. Liguori A, Esposto G, Ainora ME, Mignini I, Borriello R, Galasso L et al. Liver elastography for liver fibrosis stratification: A Comparison of three techniques in a biopsy-controlled MASLD Cohort. Biomedicines. 2025;13(1):138.

PMID: 39857722. PMCID: PMC11762890. https://doi.org/10.3390/biomedicines13010138

41. Xiao H, Shi M, Xie Y, Chi X. Comparison of diagnostic accuracy of magnetic resonance elastography and Fibroscan for detecting liver fibrosis in chronic hepatitis B patients: A systematic review and meta-analysis. PLoS One. 2017;12(11):e0186660.

PMID: 29107943. PMCID: PMC5673175. https://doi.org/10.1371/journal.pone.0186660

42. Castera L, Rinella ME, Tsochatzis EA. Noninvasive assessment of liver fibrosis. N Engl J Med. 2025;393(17):1715–29.

PMID: 41160822. https://doi.org/10.1056/NEJMra2403308

43. Honda Y, Yoneda M, Kobayashi T, Iwaki M, Kawamura N, Nogami A et al. Meta-analysis of the diagnostic accuracy of serum type IV collagen 7S concentration for the staging of liver fibrosis in nonalcoholic fatty liver disease. Hepatol Res. 2023;53(3):219–27.

PMID: 36378589. https://doi.org/10.1111/hepr.13857

44. Li W, Chi Y, Xiao X, Li J, Sun M, Sun S et al. Plasma FSTL-1 as a noninvasive diagnostic biomarker for patients with advanced liver fibrosis. Hepatology. 2025;82(3):669–82.

PMID: 40833998. PMCID: PMC12356556. https://doi.org/10.1097/HEP.0000000000001167

45. Cerrito L, Galasso L, Iaccarino J, Pizzi A, Termite F, Esposto G et al. Present and future perspectives in the treatment of liver fibrosis. Pharmaceuticals (Basel). 2025;18(9):1321.

PMID: 41011192. PMCID: PMC12472440. https://doi.org/10.3390/ph18091321

46. Qu J, Qin W, Dong M, Ma Z, Li S, Liu R et al. Liver fibrosis: Molecular pathogenesis and therapeutic interventions. MedComm. 2026;7(5):e70750.

PMID: 42087905. PMCID: PMC13136092. https://doi.org/10.1002/mco2.70750

47. Wang X, Wang L, Geng L, Tanaka N, Ye B. Resmetirom ameliorates NASH-model mice by suppressing STAT3 and NF-κB signaling pathways in an RGS5-dependent manner. Int J Mol Sci. 2023;24(6):5843.

PMID: 36982915. PMCID: PMC10058113. https://doi.org/10.3390/ijms24065843

48. Loomba R, Noureddin M, Kowdley KV, Kohli A, Sheikh A, Neff G et al.; for the ATLAS Investigators. Combination therapies including cilofexor and firsocostat for bridging fibrosis and cirrhosis attributable to NASH. Hepatology. 2021;73(2):625–43.

PMID: 33169409. https://doi.org/10.1002/hep.31622

49. Gao YS, Qian MY, Wei QQ, Duan XB, Wang SL, Hu HY et al. WZ66, a novel acetyl-CoA carboxylase inhibitor, alleviates nonalcoholic steatohepatitis (NASH) in mice. Acta Pharmacol Sin. 2020;41(3):336–47.

PMID: 31645659. PMCID: PMC7468331. https://doi.org/10.1038/s41401-019-0310-0

50. Newsome PN, Sanyal AJ, Engebretsen KA, Kliers I, Ostergaard L, Vanni D et al. Semaglutide 2.4 mg in participants with metabolic dysfunction-associated steatohepatitis: Baseline characteristics and design of the phase 3 ESSENCE trial. Aliment Pharmacol Ther. 2024;60(11–12):1525–33.

PMID: 39412509. PMCID: PMC11599791. https://doi.org/10.1111/apt.18331

51. Desjardins EM, Wu J, Lavoie DCT, Ahmadi E, Townsend LK, Morrow MR et al. Combination of an ACLY inhibitor with a GLP-1R agonist exerts additive benefits on nonalcoholic steatohepatitis and hepatic fibrosis in mice. Cell Rep Med. 202;4(9):101193.

PMID: 37729871. PMCID: PMC10518624. https://doi.org/10.1016/j.xcrm.2023.101193

52. Brown E, Heerspink HJL, Cuthbertson DJ, Wilding JPH. SGLT2 inhibitors and GLP-1 receptor agonists: Established and emerging indications. Lancet. 2021;398(10296):262–76.

PMID: 34216571. https://doi.org/10.1016/S0140-6736(21)00536-5

53. Nguyen G, Park SY, Le CT, Park WS, Choi DH, Cho EH. Metformin ameliorates activation of hepatic stellate cells and hepatic fibrosis by succinate and GPR91 inhibition. Biochem Biophys Res Commun. 2018;495(4):2649–56.

PMID: 29278707. https://doi.org/10.1016/j.bbrc.2017.12.143

54. Puengel T, Tacke F. Efruxifermin, an investigational treatment for fibrotic or cirrhotic nonalcoholic steatohepatitis (NASH). Expert Opin Investig Drugs. 2023;32(6):451–61.

PMID: 37376813. https://doi.org/10.1080/13543784.2023.2230115

55. Loomba R, Sanyal AJ, Kowdley KV, Bhatt DL, Alkhouri N, Frias JP et al. Randomized, controlled trial of the FGF21 analogue pegozafermin in NASH. N Engl J Med. 2023;389(11):998–1008.

PMID: 37356033. PMCID: PMC10718287. https://doi.org/10.1056/NEJMoa2304286

56. Ye HL, Zhang JW, Chen XZ, Wu PB, Chen L, Zhang G. Ursodeoxycholic acid alleviates experimental liver fibrosis involving inhibition of autophagy. Life Sci. 2020;242:117175.

PMID: 31843528. https://doi.org/10.1016/j.lfs.2019.117175

57. Sanyal AJ, Ratziu V, Loomba R, Anstee QM, Kowdley KV, Rinella ME et al. Results from a new efficacy and safety analysis of the REGENERATE trial of obeticholic acid for treatment of pre-cirrhotic fibrosis due to non-alcoholic steatohepatitis. J Hepatol. 2023;79(5):1110–20.

PMID: 37517454. https://doi.org/10.1016/j.jhep.2023.07.014

58. Loomba R, Bedossa P, Grimmer K, Kemble G, Bruno Martins E, McCulloch W et al. Denifanstat for the treatment of metabolic dysfunction-associated steatohepatitis: a multicentre, double-blind, randomised, placebo-controlled, phase 2b trial. Lancet Gastroenterol Hepatol. 2024;9(12):1090–100.

PMID: 39396529. https://doi.org/10.1016/S2468-1253(24)00246-2

59. Okanoue T, Sakamoto M, Harada K, Inagaki M, Totsuka N, Hashimoto G, Kumada H. Efficacy and safety of apararenone (MT-3995) in patients with nonalcoholic steatohepatitis: A randomized controlled study. Hepatol Res. 2021;51(9):943–56.

PMID: 34260795. https://doi.org/10.1111/hepr.13695

60. Fraser DA, Wang X, Lund J, Nikolic N, Iruarrizaga-Lejarreta M, Skjaeret T et al. A structurally engineered fatty acid, icosabutate, suppresses liver inflammation and fibrosis in NASH. J Hepatol. 2022;76(4):800–11.

PMID: 34915054. https://doi.org/10.1016/j.jhep.2021.12.004

61. Scorletti E, Creasy KT, Vujkovic M, Vell M, Zandvakili I, Rader DJ et al. Dietary vitamin E intake is associated with a reduced risk of developing digestive diseases and nonalcoholic fatty liver disease. Am J Gastroenterol. 2022;117(6):927–30.

PMID: 35288522. PMCID: PMC9177739. https://doi.org/10.14309/ajg.0000000000001726

62. Choi J, Nguyen VH, Przybyszewski E, Song J, Carroll A, Michta M et al. Statin use and risk of hepatocellular carcinoma and liver fibrosis in chronic liver disease. JAMA Intern Med. 2025;185(5):522–30.

PMID: 40094696. PMCID: PMC11915111. https://doi.org/10.1001/jamainternmed.2025.0115

63. Navarro VJ, Belle SH, D’Amato M, Afdhal N, Brunt EM, Fried MW et al.; Silymarin in NASH and C Hepatitis (SyNCH) Study Group. Silymarin in non-cirrhotics with non-alcoholic steatohepatitis: A randomized, double-blind, placebo-controlled trial. PLoS ONE 2019;14(10):e0223915.

PMID: 31600349. PMCID: PMC6786547. https://doi.org/10.1371/journal.pone.0223915

64. Ramachandran G, Pottakkat B. Probiotics – a promising novel therapeutic approach in the management of chronic liver diseases. J Med Food. 2024;27(6):467–76.

PMID: 38574254. https://doi.org/10.1089/jmf.2023.K.0129

65. Israelsen M, Madsen BS, Torp N, Johansen S, Hansen CD, Detlefsen S et al.; GALAXY; MicrobLiver Consortia. Rifaximin-α for liver fibrosis in patients with alcohol-related liver disease (GALA-RIF): A randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Gastroenterol Hepatol. 2023;8(6):523–32.

PMID: 36893774. PMCID: PMC10172147. https://doi.org/10.1016/S2468-1253(23)00010-9

66. Ng SC, Xu Z, Mak JWY, Yang K, Liu Q, Zuo T et al. Microbiota engraftment after faecal microbiota transplantation in obese subjects with type 2 diabetes: A 24-week, double-blind, randomised controlled trial. Gut. 2022;71(4):716–23.

PMID: 33785557. https://doi.org/10.1136/gutjnl-2020-323617

67. Tsitrina AA, Halimani N, Andreichenko IN, Sabirov M, Nesterchuk M, Dashenkova NO et al. 4-methylumbelliferone targets revealed by public data analysis and liver transcriptome sequencing. Int J Mol Sci. 2023;24(3):2129.

PMID: 36768453. PMCID: PMC9917189. https://doi.org/10.3390/ijms24032129

68. Плотникова Е.Ю., Вологжанина Л.Г., Азанов А., Сухих А.С. Коморбидность заболеваний печени и билиарного тракта. Фарматека. 2025;32(1):76–86. (Plotnikova EYu, Vologzhanina LG, Azanov AZ, Sukhikh AS. Comorbidity of liver and biliary tract diseases. Farmateka. 2025;32(1):76–86 (In Russ.)).

EDN: SBEDSW. https://doi.org/10.18565/pharmateca.2025.1.76-86

69. Плотникова Е.Ю. Известный и неизвестный гимекромон. Consilium Medicum. 2024;26(5):324–330. (Plotnikova EYu. Known and unknown hymecromone. A review. Consilium Medicum. 2024;26(5):324–330 (In Russ.)).

EDN: OPOFNF. https://doi.org/10.26442/20751753.2024.5.202877

70. Охлобыстин А.В., Шульпекова Ю.О., Зольникова О.Ю., Ивашкин В.Т. Роль гимекромона в лечении дисфункции билиарного тракта: систематический обзор и метаанализ клинических исследований. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2026;36(2):46–58. (Okhlobystin AV, Shulpekova YuO, Zolnikova OYu, Ivashkin VT. The role of hymecromone in the treatment of biliary tract dysfunction: A systematic review and meta-analysis of clinical trials. Rossiyskiy zhurnal gastroenterologii, gepatologii, koloproktologii = Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2026;36(2):46–58 (In Russ.)).

EDN: NHKKDNю https://doi.org/10.22416/1382-4376-2026-1995-5633

71. Плотникова Е.Ю., Вологжанина Л.Г., Азанов А., Сухих А.С. Коморбидность заболеваний печени и билиарного тракта. Фарматека. 2025;32(1):76–86. (Plotnikova EYu, Vologzhanina LG, Azanov AZ, Sukhikh AS. Comorbidity of liver and biliary tract diseases. Farmateka. 2025;32(1):76–86 (In Russ.)).

EDN: SBEDSW. https://doi.org/10.18565/pharmateca.2025.1.76-86

72. Kim SM, Song GY, Shim A, Lee JH, Eom CB, Liu C et al. Hyaluronan synthase 2, a target of miR-200c, promotes carbon tetrachloride-induced acute and chronic liver inflammation via regulation of CCL3 and CCL4. Exp Mol Med. 2022;54(6):739–52.

PMID: 35662287. PMCID: PMC9256637. https://doi.org/10.1038/s12276-022-00781-5

73. Andreichenko IN, Tsitrina AA, Fokin AV, Gabdulkhakova AI, Maltsev DI, Perelman GS et al. 4-methylumbelliferone prevents liver fibrosis by affecting hyaluronan deposition, FSTL1 expression and cell localization. Int J Mol Sci. 2019;20(24):6301.

PMID: 31847129. PMCID: PMC6941058. https://doi.org/10.3390/ijms20246301

74. Kultti A, Pasonen-Seppänen S, Jauhiainen M, Rilla KJ, Karna R, Pyoria E et al. 4-Methylumbelliferone inhibits hyaluronan synthesis by depletion of cellular UDP-glucuronic acid and downregulation of hyaluronan synthase 2 and 3. Exp Cell Res. 2009;315(11):1914–23.

. PMID: 19285976. https://doi.org/10.1016/j.yexcr.2009.03.002

75. Rosser JI, Nagy N, Goel R, Kaber G, Demirdjian S, Saxena J et al. Oral hymecromone decreases hyaluronan in human study participants. J Clin Invest. 2022;132(9):e157983.

PMID: 35499083. PMCID: PMC9057598. https://doi.org/10.1172/JCI157983

76. Nagy N, Gurevich I, Kuipers HF, Ruppert SM, Marshall PL, Xie BJ et al. 4-Methylumbelliferyl glucuronide contributes to hyaluronan synthesis inhibition. J Biol Chem. 2019;294(19):7864–77.

PMID: 30914479. PMCID: PMC6514619. https://doi.org/10.1074/jbc.RA118.006166

Об авторах / Для корреспонденции

Екатерина Юрьевна Плотникова, д. м. н., профессор, профессор кафедры последипломного образования и сестринского дела, руководитель курса клинической гастроэнтерологии, ФГБОУ ВО КемГМУ Минздрава России, Кемерово, Российская Федерация.
E-mail: eka-pl@rambler.ru
ORCID: https://orcid.org/0000-0002-6150-1808
Людмила Георгиевна Вологжанина, к. м. н., доцент кафедры факультетской терапии № 1 ФГБОУ ВО ПГМУ им. академика Е.А. Вагнера Минздрава России, директор ООО «ГАСТРОЦЕНТР», Пермь, Российская Федерация.
E-mail: ludovica@mail.ru
ORCID: https://orcid.org/0000-0003-3105-4645
Софья Романовна Дружинина, врач-гастроэнтеролог ООО «ГАСТРОЦЕНТР», Пермь, Российская Федерация.
Максим Алексеевич Синьков, к. м. н., сердечно-сосудистый хирург ФГБНУ «НИИ КПССЗ», Кемерово, Российская Федерация.
E-mail: fox2you@mail.ru
ORCID: https://orcid.org/0000-0002-2494-8694. Scopus ID: 57189646155. eLibrary SPIN: 8327-3979
Юрий Васильевич Котелевцев, д. б. н., профессор ЦБМТ АНОО ВО «Сколтех», Москва, Российская Федерация.
E-mail: y.kotelevtsev@skoltech.ru
ORCID: https://orcid.org/0000-0002-7255-7794. Scopus ID: 7003856033

Также по теме