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Экспериментальная и клиническая гастроэнтерология

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Место берберина в терапии метаболического синдрома

https://doi.org/10.31146/1682-8658-ecg-218-10-95-103

Аннотация

В данной статье освещается фармакологическая активность берберина, а также его место в лечение эпидемии нынешнего времени - метаболического синдрома. В обзоре подробно рассмотрены молекулярные механизмы, позволяющие достичь противовоспалительного, антимикробного и антиоксидантного эффектов. Такой фармакологический профиль действия берберина позволяет ему оказывать положительное воздействие на течение ожирения, неалкогольной жировой болезни печени, дислипопротеинемию, микробиом кишечника, а также инсулинорезистентность. В дополнении к этому настоящая статья рассматривает основные фармакокинетические параметры и побочные эффекты химически не модифицированного берберина.

Об авторах

Е. В. Шрайнер
Новосибирский государственный университет; Институт химической биологии и фундаментальной медицины СО РАН; ГК Центр Новых медицинских технологий; “Soloways” лаборатория
Россия


А. И. Хавкин
Научно-исследовательский клинический институт детства Министерства здравоохранения Московской области; Белгородский государственный исследовательский университет Министерства науки и высшего образования Российской Федерации
Россия


К. М. Николайчук
Новосибирский государственный университет
Россия


М. Ф. Новикова
Новосибирский государственный университет
Россия


А. С. Веременко
Новосибирский государственный университет
Россия


И. Д. Левченко
Новосибирский государственный университет
Россия


Е. Е. Вергунова
Новосибирский государственный университет
Россия


А. С. Тумас
Новосибирский государственный университет
Россия


П. Я. Платонова
Новосибирский государственный университет
Россия


Д. Р. Шаймарданова
Новосибирский государственный университет
Россия


И. А. Пак
ГК Центр Новых медицинских технологий; “Soloways” лаборатория
Россия


Е. А. Покушалов
ГК Центр Новых медицинских технологий; “Soloways” лаборатория
Россия


Список литературы

1. Xu Z., Feng W., Shen Q. et al. Rhizoma Coptidis and Berberine as a Natural Drug to Combat Aging and Aging-Related Diseases via Anti-Oxidation and AMPK Activation. Aging Dis. 2017 Dec 1;8(6):760-777. doi: 10.14336/AD.2016.0620.

2. Gao Y., Wang F., Song Y. et al. The status of and trends in the pharmacology of berberine: a bibliometric review [1985-2018]. Chin Med. 2020 Jan 20;15:7. doi: 10.1186/s13020-020-0288-z.

3. Patel P. A bird’s eye view on a therapeutically ’wonder molecule’: Berberine. Phytomedicine Plus. 2021;1(3):100070. doi:10.1016/j.phyplu.2021.100070

4. Malhotra B., Kulkarni G. T., Dhiman N. et al. Recent advances on Berberis aristata emphasizing berberine alkaloid including phytochemistry, pharmacology and drug delivery system. Journal of Herbal Medicine. 2021;27:100433. doi: 10.1016/j.hermed.2021.100433.

5. Kumar A., Ekavali, Chopra K. et al. Current knowledge and pharmacological profile of berberine: An update. Eur J Pharmacol. 2015 Aug 15;761:288-97. doi: 10.1016/j.ejphar.2015.05.068.

6. Xu X., Yi H., Wu J. et al. Therapeutic effect of berberine on metabolic diseases: Both pharmacological data and clinical evidence. Biomed Pharmacother. 2021 Jan;133:110984. doi: 10.1016/j.biopha.2020.110984.

7. Leng S. H., Lu F. E., Xu L. J. Therapeutic effects of berberine in impaired glucose tolerance rats and its influence on insulin secretion. Acta Pharmacol Sin. 2004 Apr;25(4):496-502.

8. Zhang Q., Xiao X., Li M. et al. Berberine moderates glucose metabolism through the GnRH-GLP-1 and MAPK pathways in the intestine. BMC Complement Altern Med. 2014 Jun 9;14:188. doi: 10.1186/1472-6882-14-188.

9. Jiang S. J., Dong H., Li J. B. et al. Berberine inhibits hepatic gluconeogenesis via the LKB1-AMPK-TORC2 signaling pathway in streptozotocin-induced diabetic rats. World J Gastroenterol. 2015 Jul 7;21(25):7777-85. doi: 10.3748/wjg.v21.i25.7777.

10. Zhong Y., Jin J., Liu P. et al. Berberine Attenuates Hyperglycemia by Inhibiting the Hepatic Glucagon Pathway in Diabetic Mice. Oxid Med Cell Longev. 2020 Jan 3;2020:6210526. doi: 10.1155/2020/6210526.

11. Xu M., Xiao Y., Yin J. et al. Berberine promotes glucose consumption independently of AMP-activated protein kinase activation. PLoS One. 2014 Jul 29;9(7): e103702. doi: 10.1371/journal.pone.0103702.

12. Donath M. Y., Shoelson S. E. Type 2 diabetes as an inflammatory disease. Nat Rev Immunol. 2011 Feb;11(2):98-107. doi: 10.1038/nri2925.

13. Hirabara S. M., Gorjão R., Vinolo M. A. et al. Molecular targets related to inflammation and insulin resistance and potential interventions. J Biomed Biotechnol. 2012;2012:379024. doi: 10.1155/2012/379024.

14. Chandirasegaran G., Elanchezhiyan C., Ghosh K. et al. Berberine chloride ameliorates oxidative stress, inflammation and apoptosis in the pancreas of Streptozotocin induced diabetic rats. Biomed Pharmacother. 2017 Nov;95:175-185. doi: 10.1016/j.biopha.2017.08.040.

15. Ma X., Chen Z., Wang L. et al. The Pathogenesis of Diabetes Mellitus by Oxidative Stress and Inflammation: Its Inhibition by Berberine. Front Pharmacol. 2018 Jul 27;9:782. doi: 10.3389/fphar.2018.00782.

16. Mo C., Wang L., Zhang J. et al. The crosstalk between Nrf2 and AMPK signal pathways is important for the anti-inflammatory effect of berberine in LPS-stimulated macrophages and endotoxin-shocked mice. Antioxid Redox Signal. 2014 Feb 1;20(4):574-88. doi: 10.1089/ars.2012.5116.

17. Gong J., Li J., Dong H., Chen G., Qin X., Hu M. et al. Inhibitory effects of berberine on proinflammatory M1 macrophage polarization through interfering with the interaction between TLR4 and MyD88. BMC Complement Altern Med. 2019 Nov 19;19(1):314. doi: 10.1186/s12906-019-2710-6.

18. Xu T., Kuang T., Du H., Li Q., Feng T., Zhang Y., Fan G. Magnoflorine: A review of its pharmacology, pharmacokinetics and toxicity. Pharmacol Res. 2020 Feb;152:104632. doi: 10.1016/j.phrs.2020.104632.

19. Xu J. H., Liu X. Z., Pan W. et al. Berberine protects against diet-induced obesity through regulating metabolic endotoxemia and gut hormone levels. Mol Med Rep. 2017 May;15(5):2765-2787. doi: 10.3892/mmr.2017.6321.

20. Wang L., Ye X., Hua Y. et al. Berberine alleviates adipose tissue fibrosis by inducing AMP-activated kinase signaling in high-fat diet-induced obese mice. Biomed Pharmacother. 2018 Sep;105:121-129. doi: 10.1016/j.biopha.2018.05.110.

21. Hu M., Wu F., Luo J. et al. The Role of Berberine in the Prevention of HIF-1α Activation to Alleviate Adipose Tissue Fibrosis in High-Fat-Diet-Induced Obese Mice. Evid Based Complement Alternat Med. 2018 Dec 2;2018:4395137. doi: 10.1155/2018/4395137.

22. Leitner B. P., Huang S., Brychta R. J. et al. Mapping of human brown adipose tissue in lean and obese young men. Proc Natl Acad Sci U S A. 2017 Aug 8;114(32):8649-8654. doi: 10.1073/pnas.1705287114.

23. Zhang Z., Zhang H., Li B. et al. Berberine activates thermogenesis in white and brown adipose tissue. Nat Commun. 2014 Nov 25;5:5493. doi: 10.1038/ncomms6493.

24. Wu L., Xia M., Duan Y. et al. Berberine promotes the recruitment and activation of brown adipose tissue in mice and humans. Cell Death Dis. 2019 Jun 13;10(6):468. doi: 10.1038/s41419-019-1706-y.

25. Guo T., Woo S. L., Guo X., Li H., Zheng J., Botchlett R. et al. Berberine Ameliorates Hepatic Steatosis and Suppresses Liver and Adipose Tissue Inflammation in Mice with Diet-induced Obesity. Sci Rep. 2016 Mar 3;6:22612. doi: 10.1038/srep22612.

26. Lin J., Cai Q., Liang B. et al. Berberine, a Traditional Chinese Medicine, Reduces Inflammation in Adipose Tissue, Polarizes M2 Macrophages, and Increases Energy Expenditure in Mice Fed a High-Fat Diet. Med Sci Monit. 2019 Jan 4;25:87-97. doi: 10.12659/MSM.911849.

27. Zhang X., Zhao Y., Xu J. et al. Modulation of gut microbiota by berberine and metformin during the treatment of high-fat diet-induced obesity in rats. Sci Rep. 2015 Sep 23;5:14405. doi: 10.1038/srep14405.

28. Cui H. X., Hu Y. N., Li J. W. et al. Hypoglycemic Mechanism of the Berberine Organic Acid Salt under the Synergistic Effect of Intestinal Flora and Oxidative Stress. Oxid Med Cell Longev. 2018 Dec 19;2018:8930374. doi: 10.1155/2018/8930374.

29. Yue S. J., Liu J., Wang A. T. et al. Berberine alleviates insulin resistance by reducing peripheral branched-chain amino acids. Am J Physiol Endocrinol Metab. 2019 Jan 1;316(1): E73-E85. doi: 10.1152/ajpendo.00256.2018.

30. Zhang W., Xu J. H., Yu T. et al. Effects of berberine and metformin on intestinal inflammation and gut microbiome composition in db/db mice. Biomed Pharmacother. 2019 Oct;118:109131. doi: 10.1016/j.biopha.2019.109131.

31. Xie W., Gu D., Li J. et al. Effects and action mechanisms of berberine and Rhizoma coptidis on gut microbes and obesity in high-fat diet-fed C57BL/6J mice. PLoS One. 2011;6(9): e24520. doi: 10.1371/journal.pone.0024520.

32. Sun H., Wang N., Cang Z., Zhu C., Zhao L., Nie X., Cheng J., Xia F., Zhai H., Lu Y. Modulation of Microbiota-Gut-Brain Axis by Berberine Resulting in Improved Metabolic Status in High-Fat Diet-Fed Rats. Obes Facts. 2016;9(6):365-378. doi: 10.1159/000449507.

33. Zhang Y., Yan J., Zhang P. et al. Berberine maintains gut microbiota homeostasis and ameliorates liver inflammation in experimental non-alcoholic fatty liver disease. Chinese Journal of Gastroenterology. 2018;23:209-215. doi: 10.3969/j.issn.1008-7125.2018.04.004.

34. Li D., Zheng J., Hu Y. et al. Amelioration of Intestinal Barrier Dysfunction by Berberine in the Treatment of Nonalcoholic Fatty Liver Disease in Rats. Pharmacogn Mag. 2017 Oct-Dec;13(52):677-682. doi: 10.4103/pm.pm_584_16.

35. Sun R., Yang N., Kong B., Cao B., Feng D., Yu X. et al. Orally Administered Berberine Modulates Hepatic Lipid Metabolism by Altering Microbial Bile Acid Metabolism and the Intestinal FXR Signaling Pathway. Mol Pharmacol. 2017 Feb;91(2):110-122. doi: 10.1124/mol.116.106617.

36. Tian Y., Cai J., Gui W. et al. Berberine Directly Affects the Gut Microbiota to Promote Intestinal Farnesoid X Receptor Activation. Drug Metab Dispos. 2019 Feb;47(2):86-93. doi: 10.1124/dmd.118.083691.

37. Zhang Z., Li B., Meng X. et al. Berberine prevents progression from hepatic steatosis to steatohepatitis and fibrosis by reducing endoplasmic reticulum stress. Sci Rep. 2016 Feb 9;6:20848. doi: 10.1038/srep20848.

38. Zhang Y. P., Deng Y. J., Tang K. R. et al. Berberine Ameliorates High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Rats via Activation of SIRT3/AMPK/ACC Pathway. Curr Med Sci. 2019 Feb;39(1):37-43. doi: 10.1007/s11596-019-1997-3.

39. Liu Y. N., Zhang Z. X. Effect of berberine on a cellular model of non-alcoholic fatty liver disease.Int J Clin Exp Med. 2017;10(12):16360-16366.

40. Zhu X., Bian H., Wang L. et al. Berberine attenuates nonalcoholic hepatic steatosis through the AMPK-SREBP-1c-SCD1 pathway. Free Radic Biol Med. 2019 Sep;141:192-204. doi: 10.1016/j.freeradbiomed.2019.06.019.

41. Xu X., Zhu X. P., Bai J. Y. et al. Berberine alleviates nonalcoholic fatty liver induced by a high-fat diet in mice by activating SIRT3. FASEB J. 2019 Jun;33(6):7289-7300. doi: 10.1096/fj.201802316R.

42. Yang J., Ma X. J., Li L. et al. Berberine ameliorates non-alcoholic steatohepatitis in ApoE-/- mice. Exp Ther Med. 2017 Nov;14(5):4134-4140. doi: 10.3892/etm.2017.5051.

43. Zhao J., Wang Y., Wu X. et al. Inhibition of CCL19 benefits non alcoholic fatty liver disease by inhibiting TLR4/NF κB p65 signaling. Mol Med Rep. 2018 Nov;18(5):4635-4642. doi: 10.3892/mmr.2018.9490.

44. Luo Y., Tian G., Zhuang Z. et al. Berberine prevents non-alcoholic steatohepatitis-derived hepatocellular carcinoma by inhibiting inflammation and angiogenesis in mice. Am J Transl Res. 2019 May 15;11(5):2668-2682.

45. Guo T., Woo S. L., Guo X., Li H., Zheng J., Botchlett R. et al. Berberine Ameliorates Hepatic Steatosis and Suppresses Liver and Adipose Tissue Inflammation in Mice with Diet-induced Obesity. Sci Rep. 2016 Mar 3;6:22612. doi: 10.1038/srep22612.

46. Ashrafizadeh M., Fekri H. S., Ahmadi Z. et al. Therapeutic and biological activities of berberine: The involvement of Nrf2 signaling pathway. J Cell Biochem. 2020 Feb;121(2):1575-1585. doi: 10.1002/jcb.29392.

47. Dinesh P., Rasool M. Berberine, an isoquinoline alkaloid suppresses TXNIP mediated NLRP3 inflammasome activation in MSU crystal stimulated RAW 264.7 macrophages through the upregulation of Nrf2 transcription factor and alleviates MSU crystal induced inflammation in rats.Int Immunopharmacol. 2017 Mar;44:26-37. doi: 10.1016/j.intimp.2016.12.031.

48. Deng Y., Tang K., Chen R. et al. Berberine attenuates hepatic oxidative stress in rats with non-alcoholic fatty liver disease via the Nrf2/ARE signalling pathway. Exp Ther Med. 2019 Mar;17(3):2091-2098. doi: 10.3892/etm.2019.7208.

49. Mahmoud A. M., Hozayen W. G., Ramadan S. M. Berberine ameliorates methotrexate-induced liver injury by activating Nrf2/HO-1 pathway and PPARγ, and suppressing oxidative stress and apoptosis in rats. Biomed Pharmacother. 2017 Oct;94:280-291. doi: 10.1016/j.biopha.2017.07.101.

50. Wang Y., Tong Q., Shou J. W. et al. Gut Microbiota-Mediated Personalized Treatment of Hyperlipidemia Using Berberine. Theranostics. 2017 Jun 24;7(9):2443-2451. doi: 10.7150/thno.18290.

51. Li Z., Jiang J. D., Kong W. J. Berberine up-regulates hepatic low-density lipoprotein receptor through Ras-independent but AMP-activated protein kinase-dependent Raf-1 activation. Biol Pharm Bull. 2014;37(11):1766-75. doi: 10.1248/bpb.b14-00412.

52. Li X. Y., Zhao Z. X., Huang M., Feng R., He C. Y., Ma C., et al. Effect of Berberine on promoting the excretion of cholesterol in high-fat diet-induced hyperlipidemic hamsters. J Transl Med. 2015 Aug 27;13:278. doi: 10.1186/s12967-015-0629-3.

53. Li M., Shu X., Xu H. et al.Integrative analysis of metabolome and gut microbiota in diet-induced hyperlipidemic rats treated with berberine compounds. J Transl Med. 2016 Aug 5;14(1):237. doi: 10.1186/s12967-016-0987-5.

54. Wang Y., Yang R., Shan L. Efficacy and safety of berberine combined with benzbromarone in the treatment of hyperuricemia with gout. Chin J Mod Drug Appl. 2018;12(7):3-6. doi: 10.14164/j.cnki.cn11-5581/r.2018.17.002.

55. Liu Y. F., Wen C. Y., Chen Z. et al. Effects of Berberine on NLRP3 and IL-1β Expressions in Monocytic THP-1 Cells with Monosodium Urate Crystals-Induced Inflammation. Biomed Res Int. 2016;2016:2503703. doi: 10.1155/2016/2503703.

56. Almatroodi S. A., Alsahli M. A., Rahmani A. H. Berberine: An Important Emphasis on Its Anticancer Effects through Modulation of Various Cell Signaling Pathways. Molecules. 2022 Sep 10;27(18):5889. doi: 10.3390/molecules27185889.

57. Lin C. C., Lin S. Y., Chung J. G., Lin J. P., Chen G. W., Kao S. T. Down-regulation of cyclin B1 and up-regulation of Wee1 by berberine promotes entry of leukemia cells into the G2/M-phase of the cell cycle. Anticancer Res. 2006 Mar-Apr;26(2A):1097-104.

58. Letasiová S., Jantová S., Cipák L. et al. Berberine-antiproliferative activity in vitro and induction of apoptosis/necrosis of the U937 and B16 cells. Cancer Lett. 2006 Aug 8;239(2):254-62. doi: 10.1016/j.canlet.2005.08.024.

59. Yang X., Huang N. Berberine induces selective apoptosis through the AMPK-mediated mitochondrial/caspase pathway in hepatocellular carcinoma. Mol Med Rep. 2013 Aug;8(2):505-10. doi: 10.3892/mmr.2013.1506.

60. Hu H. Y., Li K. P., Wang X. J. et al. Set9, NF-κB, and microRNA-21 mediate berberine-induced apoptosis of human multiple myeloma cells. Acta Pharmacol Sin. 2013 Jan;34(1):157-66. doi: 10.1038/aps.2012.161.

61. Wang J., Qi Q., Feng Z., Zhang X., Huang B., Chen A. et al. Berberine induces autophagy in glioblastoma by targeting the AMPK/mTOR/ULK1-pathway. Oncotarget. 2016 Oct 11;7(41):66944-66958. doi: 10.18632/oncotarget.11396.

62. Palmieri A., Scapoli L., Iapichino A., Mercolini L., Mandrone M., Poli F. et al. Berberine and Tinospora cordifolia exert a potential anticancer effect on colon cancer cells by acting on specific pathways.Int J Immunopathol Pharmacol. 2019 Jan-Dec;33:2058738419855567. doi: 10.1177/2058738419855567.

63. Yang X. J., Liu F., Feng N. et al. Berberine Attenuates Cholesterol Accumulation in Macrophage Foam Cells by Suppressing AP-1 Activity and Activation of the Nrf2/HO-1 Pathway. J Cardiovasc Pharmacol. 2020 Jan;75(1):45-53. doi: 10.1097/FJC.0000000000000769.

64. Imenshahidi M., Hosseinzadeh H. Berberine and barberry (Berberis vulgaris): A clinical review. Phytother Res. 2019 Mar;33(3):504-523. doi: 10.1002/ptr.6252.

65. Spinozzi S., Colliva C., Camborata C., Roberti M., Ianni C., Neri F. et al. Berberine and its metabolites: relationship between physicochemical properties and plasma levels after administration to human subjects. J Nat Prod. 2014 Apr 25;77(4):766-72. doi: 10.1021/np400607k.

66. Liu C. S., Zheng Y. R., Zhang Y. F. et al. Research progress on berberine with a special focus on its oral bioavailability. Fitoterapia. 2016 Mar;109:274-82. doi: 10.1016/j.fitote.2016.02.001.

67. Wang K., Feng X., Chai L. et al. The metabolism of berberine and its contribution to the phar-macological effects. Drug Metab Rev. 2017 May;49(2):139-157. doi: 10.1080/03602532.2017.1306544.

68. Feng X., Sureda A., Jafari S., Memariani Z., Tewari D., Annunziata G. et al. Berberine in Cardiovascular and Metabolic Diseases: From Mechanisms to Therapeutics. Theranostics. 2019 Mar 16;9(7):1923-1951. doi: 10.7150/thno.30787.

69. Lan J., Zhao Y., Dong F. et al. Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. J Ethnopharmacol. 2015 Feb 23;161:69-81. doi: 10.1016/j.jep.2014.09.049.

70. Mohammadzadeh N., Mehri S., Hosseinzadeh H. Berberis vulgaris and its constituent berberine as antidotes and protective agents against natural or chemical toxicities. Iran J Basic Med Sci. 2017 May;20(5):538-551. doi: 10.22038/IJBMS.2017.8678.

71. Yi J., Ye X., Wang D. et al. Safety evaluation of main alkaloids from Rhizoma Coptidis. J Ethnopharmacol. 2013 Jan 9;145(1):303-10. doi: 10.1016/j.jep.2012.10.062.

72. Yin J., Xing H., Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. 2008 May;57(5):712-7. doi: 10.1016/j.metabol.2008.01.013.


Рецензия

Для цитирования:


Шрайнер Е.В., Хавкин А.И., Николайчук К.М., Новикова М.Ф., Веременко А.С., Левченко И.Д., Вергунова Е.Е., Тумас А.С., Платонова П.Я., Шаймарданова Д.Р., Пак И.А., Покушалов Е.А. Место берберина в терапии метаболического синдрома. Экспериментальная и клиническая гастроэнтерология. 2023;(10):95-103. https://doi.org/10.31146/1682-8658-ecg-218-10-95-103

For citation:


Shrayner E.V., Khavkin A.I., Nikolaychuk K.M., Novikova M.F., Veremenko A.S., Levchenko I.D., Vergunova E.E., Tumas A.S., Platonova P.Ya., Shaimardanova D.R., Pak I.A., Pokushalov E.A. The place of berberine in the treatment of metabolic syndrome. Experimental and Clinical Gastroenterology. 2023;(10):95-103. (In Russ.) https://doi.org/10.31146/1682-8658-ecg-218-10-95-103

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