Глифлозины как средства коррекции неврологических осложнений неалкогольной жировой болезни печени. Часть 2


DOI: https://dx.doi.org/10.18565/therapy.2024.5.150-160

В.А. Приходько, С.В. Оковитый

1) ФГБОУ ВО «Санкт-Петербургский государственный химико-фармацевтический университет» Минздрава России; 2) ФГБОУ ВО «Санкт-Петербургский государственный университет»
Аннотация. Неалкогольная жировая болезнь печени (НАЖБП) и неалкогольный стеатогепатит (НАСГ) имеют ряд общих факторов риска с поражениями центральной нервной системы, а также являются самостоятельной причиной развития цереброваскулярных, нейродегенеративных, когнитивных и психических расстройств. Статья представляет собой вторую и заключительную часть обзора литературы, посвященную молекулярным механизмам нейропротекторного действия ингибиторов натрий-глюкозных котранспортеров (глифлозинов), имеющих наибольшую значимость в контексте коррекции психоневрологических осложнений НАЖБП и НАСГ.

Литература


1. Clough G.F., Chipperfield A.J., Thanaj M. et al. Dysregulated neurovascular control underlies declining microvascular functionality in people with non-alcoholic fatty liver disease (NAFLD) at risk of liver fibrosis. Front Physiol. 2020; 11: 551.


https://doi.org/10.3389/fphys.2020.00551. PMID: 32581841. PMCID: PMC7283580.


2. Cheon S.Y., Song J. Novel insights into non-alcoholic fatty liver disease and dementia: insulin resistance, hyperammonemia, gut dysbiosis, vascular impairment, and inflammation. Cell Biosci. 2022; 12(1): 99.


https://doi.org/10.1186/s13578-022-00836-0. PMID: 35765060. PMCID: PMC9237975.


3. Hayden M.R., Grant D.G., Aroor A.R., DeMarco V.G. Empagliflozin ameliorates type 2 diabetes-induced ultrastructural remodeling of the neurovascular unit and neuroglia in the female db/db mouse. Brain Sci. 2019; 9(3): 57.


https://doi.org/10.3390/brainsci9030057. PMID: 30866531. PMCID: PMC6468773.


4. Hanaguri J., Yokota H., Kushiyama A. et al. The effect of sodium-dependent glucose cotransporter 2 inhibitor tofogliflozin on neurovascular coupling in the retina in type 2 diabetic mice. Int J Mol Sci. 2022; 23(3): 1362.


https://doi.org/10.3390/ijms23031362. PMID: 35163285. PMCID: PMC8835894.


5. Tsuchida A., Nonomura T., Nakagawa T. et al. Brain-derived neurotrophic factor ameliorates lipid metabolism in diabetic mice. Diabetes Obes Metab. 2002; 4(4): 262–69.


https://doi.org/10.1046/j.1463-1326.2002.00206.x. PMID: 12099975.


6. Genzer Y., Chapnik N., Froy O. Effect of brain-derived neurotrophic factor (BDNF) on hepatocyte metabolism. Int J Biochem Cell Biol. 2017; 88: 69–74.


https://doi.org/10.1016/j.biocel.2017.05.008. PMID: 28483667.


7. Hattori Y., Yamada H., Munetsuna E. et al. Increased brain-derived neurotrophic factor in the serum of persons with nonalcoholic fatty liver disease. Endocr J. 2022; 69(8): 999–1006.


https://doi.org/10.1507/endocrj.EJ21-0584. PMID: 35354697.


8 Hashida R., Nakano D., Yamamura S. et al. Association between activity and brain-derived neurotrophic factor in patients with non-alcoholic fatty liver disease: A data-mining analysis. Life (Basel). 2021; 11(8): 799.


https://doi.org/10.3390/life11080799. PMID: 34440543. PMCID: PMC8401718.


9. Stawicka A., Swiderska M., Zbrzeźniak J. et al. Brain-derived neurotrophic factor as a potential diagnostic marker in minimal hepatic encephalopathy. Clin Exp Hepatol. 2021; 7(1): 117–24.


https://doi.org/10.5114/ceh.2021.103242. PMID: 34027124. PMCID: PMC8122095.


10. Sepehrinezhad A., Shahbazi A., Sahab Negah S., Stolze Larsen F. New insight into mechanisms of hepatic encephalopathy: An integrative analysis approach to identify molecular markers and therapeutic targets. Bioinform Biol Insights. 2023; 17: 11779322231155068.


https://doi.org/10.1177/11779322231155068. PMID: 36814683. PMCID: PMC9940182.


11. Suliman S., Hemmings S.M., Seedat S. Brain-derived neurotrophic factor (BDNF) protein levels in anxiety disorders: Systematic review and meta-regression analysis. Front Integr Neurosci. 2013; 7: 55.


https://doi.org/10.3389/fnint.2013.00055. PMID: 23908608. PMCID: PMC3725410.


12. Porter G.A., O’Connor J.C. Brain-derived neurotrophic factor and inflammation in depression: Pathogenic partners in crime? World J Psychiatry. 2022; 12(1): 77–97.


https://doi.org/10.5498/wjp.v12.i1.77. PMID: 35111580. PMCID: PMC8783167.


13. Gangopadhyay A., Ibrahim R., Theberge K. et al. Non-alcoholic fatty liver disease (NAFLD) and mental illness: Mechanisms linking mood, metabolism and medicines. Front Neurosci. 2022; 16: 1042442.


https://doi.org/10.3389/fnins.2022.1042442. PMID: 36458039. PMCID: PMC9707801.


14. Cao T., Matyas J.J., Renn C.L. et al. Function and mechanisms of truncated BDNF receptor TrkB.T1 in neuropathic pain. Cells. 2020; 9(5): 1194.


https://doi.org/10.3390/cells9051194. PMID: 32403409. PMCID: PMC7290366.


15. Zhang J.C., Yao W., Hashimoto K. Brain-derived neurotrophic factor (BDNF)-TrkB signaling in inflammation-related depression and potential therapeutic targets. Curr Neuropharmacol. 2016; 14(7): 721–31.


https://doi.org/10.2174/1570159x14666160119094646. PMID: 26786147. PMCID: PMC5050398.


16. Wang H.Y., Stucky A., Hahn C.G. et al. BDNF-trkB signaling in late life cognitive decline and Alzheimer’s disease. Translational Neuroscience. 2011; 2(2): 91–100.


https://doi.org/10.2478/s13380-011-0015-4.


17. Ye S., Xie D.J., Zhou P. et al. Huang-Pu-Tong-Qiao formula ameliorates the hippocampus apoptosis in diabetic cognitive dysfunction mice by activating CREB/BDNF/TrkB signaling pathway. Evid Based Complement Alternat Med. 2021; 2021: 5514175.


https://doi.org/10.1155/2021/5514175. PMID: 34211563. PMCID: PMC8211510.


18. Saral S., Topçu A., Alkanat M. et al. Apelin-13 activates the hippocampal BDNF/TrkB signaling pathway and suppresses neuroinflammation in male rats with cisplatin-induced cognitive dysfunction. Behav Brain Res. 2021; 408: 113290.


https://doi.org/10.1016/j.bbr.2021.113290. PMID: 33845103.


19. Piątkowska-Chmiel I., Herbet M., Gawrońska-Grzywacz M. et al. Molecular and neural roles of sodium-glucose cotransporter 2 inhibitors in alleviating neurocognitive impairment in diabetic mice. Psychopharmacology (Berl). 2023; 240(4): 983–1000.


https://doi.org/10.1007/s00213-023-06341-7. PMID: 36869919. PMCID: PMC10006050.


20. Mousa H.H., Sharawy M.H., Nader M.A. Empagliflozin enhances neuroplasticity in rotenone-induced parkinsonism: Role of BDNF, CREB and Npas4. Life Sci. 2023; 312: 121258.


https://doi.org/10.1016/j.lfs.2022.121258. PMID: 36462721.


21. Lin B., Koibuchi N., Hasegawa Y. et al. Glycemic control with empagliflozin, a novel selective SGLT2 inhibitor, ameliorates cardiovascular injury and cognitive dysfunction in obese and type 2 diabetic mice. Cardiovasc Diabetol. 2014; 13: 148.


https://doi.org/10.1186/s12933-014-0148-1. PMID: 25344694. PMCID: PMC4219031.


22. Millar P., Pathak N., Parthsarathy V. et al. Metabolic and neuroprotective effects of dapagliflozin and liraglutide in diabetic mice. J Endocrinol. 2017; 234(3): 255–67.


https://doi.org/10.1530/JOE-17-0263. PMID: 28611211.


23. Mohammed S.K., Magdy Y.M., El-Waseef D.A. et al. Modulation of hippocampal TLR4/BDNF signal pathway using probiotics is astep closer towards treating cognitive impairment in NASH model. Physiol Behav. 2020; 214: 112762.


https://doi.org/10.1016/j.physbeh.2019.112762. PMID: 31786271.


24. Sharifnia T., Antoun J., Verriere T.G. et al. Hepatic TLR4 signaling in obese NAFLD. Am J Physiol Gastrointest Liver Physiol. 2015; 309(4): G270–G278.


https://doi.org/10.1152/ajpgi.00304.2014. PMID: 26113297. PMCID: PMC4537925.


25. Sun B.L., Sun X., Kempf C.L. et al. Involvement of eNAMPT/TLR4 inflammatory signaling in progression of non-alcoholic fatty liver disease, steatohepatitis, and fibrosis. FASEB J. 2023; 37(3): e22825.


https://doi.org/10.1096/fj.202201972RR. PMID: 36809677.


26. Yi M., Zhou J., Sun H. et al. Correlation between TLR4 expression and gene polymorphism in peripheral blood mononuclear cells and condition of nonalcoholic fatty acid disease in Han people of Shaanxi. Int J Clin Exp Pathol. 2017; 10(3): 3496–3502.


27. Shi X.Y., Zheng X.M., Liu H.J. et al. Rotundic acid improves nonalcoholic steatohepatitis in mice by regulating glycolysis and the TLR4/AP1 signaling pathway. Lipids Health Dis. 2023; 22(1): 214.


https://doi.org/10.1186/s12944-023-01976-z. PMID: 38049817. PMCID: PMC10694891.


28. Liu H., Li N., Kuang G. et al. Protectin D1 inhibits TLR4 signaling pathway to alleviate non-alcoholic steatohepatitis via upregulating IRAK-M. Free Radic Biol Med. 2024; 210: 42–53.


https://doi.org/10.1016/j.freeradbiomed.2023.11.011. PMID: 37984750.


29. Zhou Y., Chen Y., Xu C. et al. TLR4 Targeting as a Promising Therapeutic Strategy for Alzheimer Disease Treatment. Front Neurosci. 2020; 14: 602508.


https://doi.org/10.3389/fnins.2020.602508. PMID: 33390886. PMCID: PMC7775514.


30. Connolly M.G., Potter O.V., Sexton A.R., Kohman R.A. Effects of Toll-like receptor 4 inhibition on spatial memory and cell proliferation in male and female adult and aged mice. Brain Behav Immun. 2021; 97: 383–93.


https://doi.org/10.1016/j.bbi.2021.06.008. PMID: 34343615. PMCID: PMC8453097.


31. Fei X., Dou Y.N., Lv W. et al. TLR4 deletion improves cognitive brain function and structure in aged mice. Neuroscience. 2022; 492: 1–17.


https://doi.org/10.1016/j.neuroscience.2022.04.007. PMID: 35405301.


32. Obadia N., Andrade G., Leardini-Tristao M. et al. TLR4 mutation protects neurovascular function and cognitive decline in high-fat diet-fed mice. J Neuroinflammation. 2022; 19(1): 104.


https://doi.org/10.1186/s12974-022-02465-3. PMID: 35488354. PMCID: PMC9052472.


33. Zou H., Chen X., Lu J. et al. Neurotropin alleviates cognitive impairment by inhibiting TLR4/MyD88/NF-κB inflammation signaling pathway in mice with vascular dementia. Neurochem Int. 2023; 171: 105625.


https://doi.org/10.1016/j.neuint.2023.105625. PMID: 37774797.


34. Lu B., Wu C., Azami N.L.B. et al. Babao Dan improves neurocognitive function by inhibiting inflammation in clinical minimal hepatic encephalopathy. Biomed Pharmacother. 2021; 135: 111084.


https://doi.org/10.1016/j.biopha.2020.111084. PMID: 33383371.


35. Shelke V., Kale A., Dagar N. et al. Concomitant inhibition of TLR-4 and SGLT2 by phloretin and empagliflozin prevents diabetes-associated ischemic acute kidney injury. Food Funct. 2023; 14(11): 5391–5403.


https://doi.org/10.1039/d3fo01379k. PMID: 37218423.


36. Kuno A., Kimura Y., Mizuno M. et al. Empagliflozin attenuates acute kidney injury after myocardial infarction in diabetic rats. Sci Rep. 2020; 10(1): 7238.


https://doi.org/10.1038/s41598-020-64380-y. PMID: 32350374. PMCID: PMC7190820.


37. Abdollahi E., Keyhanfar F., Delbandi A.A. et al. Dapagliflozin exerts anti-inflammatory effects via inhibition of LPS-induced TLR-4 overexpression and NF-κB activation in human endothelial cells and differentiated macrophages. Eur J Pharmacol. 2022; 918: 174715.


https://doi.org/10.1016/j.ejphar.2021.174715. PMID: 35026193.


38. Abdelmageed M.E., Abdelrahman R.S. Canagliflozin attenuates thioacetamide-induced liver injury through modulation of HMGB1/RAGE/TLR4 signaling pathways. Life Sci. 2023; 322: 121654.


https://doi.org/10.1016/j.lfs.2023.121654. PMID: 37023955.


39. Althagafy H.S., Ali F.E.M., Hassanein E.H.M. et al. Canagliflozin ameliorates ulcerative colitis via regulation of TLR4/MAPK/NF-κB and Nrf2/PPAR-γ/SIRT1 signaling pathways. Eur J Pharmacol. 2023; 960: 176166.


https://doi.org/10.1016/j.ejphar.2023.176166. PMID: 37898288.


40. Abd Uljaleel A.Q., Hassan E.S. Protective Effect of Ertugliflozin against acute lung injury caused by endotoxemia model in mice. Iranian Journal of War and Public Health. 2023; 15(1): 67–75.


https://doi.org/10.58209/ijwph.15.1.67.


41. Gong Y., Kong B., Shuai W. et al. Effect of sotagliflozin on ventricular arrhythmias in mice with myocardial infraction. EurJ Pharmacol. 2022; 936: 175357.


https://doi.org/10.1016/j.ejphar.2022.175357. PMID: 36330901.


42. Qin Z.Y., Gu X., Chen Y.L. et al. Toll‑like receptor 4 activates the NLRP3 inflammasome pathway and periodontal inflammaging by inhibiting Bmi‑1 expression. Int J Mol Med. 2021; 47(1): 137–50.


https://doi.org/10.3892/ijmm.2020.4787. PMID: 33236134. PMCID: PMC7723510.


43. Yu L., Hong W., Lu S. et al. The NLRP3 Inflammasome in non-alcoholic fatty liver disease and steatohepatitis: Therapeutic targets and treatment. Front Pharmacol. 2022; 13: 780496.


https://doi.org/10.3389/fphar.2022.780496. PMID: 35350750. PMCID: PMC8957978.


44. Cheon S.Y., Kim M.Y., Kim J. et al. Hyperammonemia induces microglial NLRP3 inflammasome activation via mitochondrial oxidative stress in hepatic encephalopathy. Biomed J. 2023; 46(5): 100593.


https://doi.org/10.1016/j.bj.2023.04.001. PMID: 37059364. PMCID: PMC10498413.


45. Smith C., Trageser K.J., Wu H. et al. Anxiolytic effects of NLRP3 inflammasome inhibition in a model of chronic sleep deprivation. Transl Psychiatry. 2021; 11(1): 52.


https://doi.org/10.1038/s41398-020-01189-3. PMID: 33446652. PMCID: PMC7809257.


46. Roy S., Arif Ansari M., Choudhary K., Singh S. NLRP3 inflammasome in depression: A review. Int Immunopharmacol. 2023; 117: 109916.


https://doi.org/10.1016/j.intimp.2023.109916. PMID: 36827927.


47. Zhang Z., Ma X., Xia Z. et al. NLRP3 inflammasome activation mediates fatigue-like behaviors in mice via neuroinflammation. Neuroscience. 2017; 358: 115–23.


https://doi.org/10.1016/j.neuroscience.2017.06.048. PMID: 28684277.


48. Amini M., Yousefi Z., Ghafori S.S., Hassanzadeh G. Sleep deprivation and NLRP3 inflammasome: Is there a causal relationship? Front Neurosci. 2022; 16: 1018628.


https://doi.org/10.3389/fnins.2022.1018628. PMID: 36620464. PMCID: PMC9815451.


49. Li W., Liang J., Li S. et al. Research progress of targeting NLRP3 inflammasome in peripheral nerve injury and pain. Int Immunopharmacol. 2022; 110: 109026.


https://doi.org/10.1016/j.intimp.2022.109026. PMID: 35978503.


50. Ye Y., Bajaj M., Yang H.C., Perez-Polo J.R. Birnbaum Y. SGLT-2 inhibition with dapagliflozin reduces the activation of the Nlrp3/ASC inflammasome and attenuates the development of diabetic cardiomyopathy in mice with type 2 diabetes. Further augmentation of the effects with saxagliptin, a DPP4 inhibitor. Cardiovasc Drugs Ther. 2017; 31(2): 119–32.


https://doi.org/10.1007/s10557-017-6725-2. PMID: 28447181.


51. Chen H., Tran D., Yang H.C. et al. Dapagliflozin and ticagrelor have additive effects on the attenuation of the activation of the NLRP3 inflammasome and the progression of diabetic cardiomyopathy: An AMPK-mTOR interplay. Cardiovasc Drugs Ther. 2020; 34(4): 443–61.


https://doi.org/10.1007/s10557-020-06978-y. PMID: 32335797.


52. Kim S.R., Lee S.G., Kim S.H. et al. SGLT2 inhibition modulates NLRP3 inflammasome activity via ketones and insulin in diabetes with cardiovascular disease. Nat Commun. 2020; 11(1): 2127.


https://doi.org/10.1038/s41467-020-15983-6. PMID: 32358544. PMCID: PMC7195385.


53. Pawlos A., Broncel M., Wozniak E., Gorzelak-Pabis P. Neuroprotective effect of SGLT2 inhibitors. Molecules. 2021; 26(23): 7213.


https://doi.org/10.3390/molecules26237213. PMID: 34885795. PMCID: PMC8659196.


54. Alharthi J., Latchoumanin O., George J., Eslam M. Macrophages in metabolic associated fatty liver disease. World J Gastroenterol. 2020; 26(16): 1861–78.


https://doi.org/10.3748/wjg.v26.i16.1861. PMID: 32390698. PMCID: PMC7201150.


55. Xu L., Nagata N., Nagashimada M. et al. SGLT2 inhibition by empagliflozin promotes fat utilization and browning and attenuates inflammation and insulin resistance by polarizing M2 macrophages in diet-induced obese mice. EBioMedicine. 2017; 20: 137–49.


https://doi.org/10.1016/j.ebiom.2017.05.028. PMID: 28579299. PMCID: PMC5478253.


56. Lee S.G., Lee S.J., Lee J.J. et al. Anti-Inflammatory effect for atherosclerosis progression by sodium-glucose cotransporter 2 (SGLT-2) inhibitor in a normoglycemic rabbit model. Korean Circ J. 2020; 50(5): 443–57.


https://doi.org/10.4070/kcj.2019.0296. PMID: 32153145. PMCID: PMC7098824.


57. Lee T.M., Chang N.C., Lin S.Z. Dapagliflozin, a selective SGLT2 inhibitor, attenuated cardiac fibrosis by regulating the macrophage polarization via STAT3 signaling in infarcted rat hearts. Free Radic Biol Med. 2017; 104: 298–310.


https://doi.org/10.1016/j.freeradbiomed.2017.01.035. PMID: 28132924.


58. Walczak-Nowicka Ł.J., Herbet M. Acetylcholinesterase inhibitors in the treatment of neurodegenerative diseases and the role of acetylcholinesterase in their pathogenesis. Int J Mol Sci. 2021; 22(17): 9290.


https://doi.org/10.3390/ijms22179290. PMID: 34502198. PMCID: PMC8430571.


59. Li W., Antuono P.G., Xie C. et al. Changes in regional cerebral blood flow and functional connectivity in the cholinergic pathway associated with cognitive performance in subjects with mild Alzheimer’s disease after 12-week donepezil treatment. Neuroimage. 2012; 60(2): 1083–91.


https://doi.org/10.1016/j.neuroimage.2011.12.077. PMID: 22245641. PMCID: PMC3324180.


60. Moss D.E., Perez R.G. Anti-neurodegenerative benefits of acetylcholinesterase inhibitors in Alzheimer’s disease: Nexus of cholinergic and nerve growth factor dysfunction. Curr Alzheimer Res. 2021; 18(13): 1010–22.


https://doi.org/10.2174/1567205018666211215150547. PMID: 34911424. PMCID: PMC8855657.


61. Meng F., Yin X., Ma X. et al. Assessment of the value of serum cholinesterase as a liver function test for cirrhotic patients. Biomed Rep. 2013; 1(2): 265–68.


https://doi.org/10.3892/br.2013.60. PMID: 24648933. PMCID: PMC3917072.


62. García-Ayllon M.S., Millan C., Serra-Basante C. et al. Readthrough acetylcholinesterase is increased in human liver cirrhosis. PLoS One. 2012; 7(9): e44598.


https://doi.org/10.1371/journal.pone.0044598. PMID: 23028565. PMCID: PMC3441564.


63. Kim D.G., Krenz A., Toussaint L.E. et al. Non-alcoholic fatty liver disease induces signs of Alzheimer’s disease (AD) in wild-type mice and accelerates pathological signs of AD in an AD model. J Neuroinflammation. 2016; 13: 1.


https://doi.org/10.1186/s12974-015-0467-5. PMID: 26728181. PMCID: PMC4700622.


64. Rizvi S.M., Shakil S., Biswas D. et al. Invokana (Canagliflozin) as a dual inhibitor of acetylcholinesterase and sodium glucose co-transporter 2: advancement in Alzheimer’s disease- diabetes type 2 linkage via an enzoinformatics study. CNS Neurol Disord Drug Targets. 2014; 13(3): 447–51.


https://doi.org/10.2174/18715273113126660160. PMID: 24059302.


65. Shaikh S., Rizvi S.M., Suhail T. et al. Prediction of anti-diabetic drugs as dual inhibitors against acetylcholinesterase and beta-secretase: A neuroinformatics study. CNS Neurol Disord Drug Targets. 2016; 15(10): 1216–21.


https://doi.org/10.2174/1871527315666161003125752. PMID: 27697060.


66. Shakil S. Molecular interaction of anti-diabetic drugs with acetylcholinesterase and sodium glucose co-transporter 2. J Cell Biochem. 2017; 118(11): 3855–65.


https://doi.org/10.1002/jcb.26036. PMID: 28387957.


67. Клинические рекомендации. Когнитивные расстройства у лиц пожилого и старческого возраста. Общественная организация «Российское общество психиатров», общероссийская общественная организация «Российская ассоциация геронтологов и гериатров». Рубрикатор клинических рекомендаций Минздрава России. 2020. ID: 617. Доступ: https://cr.minzdrav.gov.ru/recomend/617_1 (дата обращения – 17.06.2024). (Clinical guidelines. Cognitive disorders in the elderly and senile. Russian Association of gerontologists and geriatricians, Russian Society of Psychiatrists. Rubricator of clinical guidelines of the Ministry of Healthcare of Russia. 2020. ID: 617. URL: https://cr.minzdrav.gov.ru/recomend/617_1 (date of access – 17.06.2024) (In Russ.)).


68. Darvesh S., Walsh R., Kumar R. et al. Inhibition of human cholinesterases by drugs used to treat Alzheimer disease. Alzheimer Dis Assoc Disord. 2003; 17(2): 117–26.


https://doi.org/10.1097/00002093-200304000-00011. PMID: 12794390.


69. Arafa N.M.S., Ali E.H.A., Hassan M.K. Canagliflozin prevents scopolamine-induced memory impairment in rats: Comparison with galantamine hydrobromide action. Chem Biol Interact. 2017; 277: 195–203.


https://doi.org/10.1016/j.cbi.2017.08.013. PMID: 28837785.


70. Stanciu G.D., Ababei D.C., Solcan C. et al. Preclinical studies of canagliflozin, a sodium-glucose co-transporter 2 inhibitor, and donepezil combined therapy in Alzheimer’s disease. Pharmaceuticals (Basel). 2023; 16(11): 1620.


https://doi.org/10.3390/ph16111620. PMID: 38004485. PMCID: PMC10674192.


71. Abd-Elsalam R.M., Rizk H.A., Masoud M.A. et al. Lactulose and donepezil ameliorate thioacetamide-induced hepatic encephalopathy in rats. J Drug Res Egypt. 2014; 35(1): 21–31.


72. Kappus M.R., Bajaj J.S. Covert hepatic encephalopathy: Not as minimal as you might think. Clin Gastroenterol Hepatol. 2012; 10(11): 1208–19.


https://doi.org/10.1016/j.cgh.2012.05.026. PMID: 22728384.


73. Basu P.P., Shah N.J., Aloysius M.M., Brown R.S. Randomized, placebo-controlled trial of transdermal rivastigmine for the treatment of encephalopathy in liver cirrhosis (TREC Trial). Open Journal of Gastroenterology. 2014; 4(6): 255–64.


https://doi.org/10.4236/ojgas.2014.46038.


74. Feng J., Qiu S., Zhou S. et al. mTOR: A potential new target in nonalcoholic fatty liver disease. Int J Mol Sci. 2022; 23(16): 9196.


https://doi.org/10.3390/ijms23169196. PMID: 36012464. PMCID: PMC9409235.


75. Crino P.B. The mTOR signalling cascade: Paving new roads to cure neurological disease. Nat Rev Neurol. 2016; 12(7): 379–92.


https://doi.org/10.1038/nrneurol.2016.81. PMID: 27340022.


76. Abdelrahman R.S., El-Tanbouly G.S. Protocatechuic acid protects against thioacetamide-induced chronic liver injury and encephalopathy in mice via modulating mTOR, p53 and the IL-6/IL-17/IL-23 immunoinflammatory pathway. Toxicol Appl Pharmacol. 2022; 440: 115931.


https://doi.org/10.1016/j.taap.2022.115931. PMID: 35202709.


77. Xu T., Liu J., Li X.R. et al. The mTOR/NF-κB pathway mediates neuroinflammation and synaptic plasticity in diabetic encephalopathy. Mol Neurobiol. 2021; 58(8): 3848–62.


https://doi.org/10.1007/s12035-021-02390-1. PMID: 33860440.


78. Weinstein A.A., de Avila L., Paik J. et al. Cognitive performance in individuals with non-alcoholic fatty liver disease and/or type 2 diabetes mellitus. Psychosomatics. 2018; 59(6): 567–74.


https://doi.org/10.1016/j.psym.2018.06.001. PMID: 30086995.


79. Wu K.C., Huang H.C., Chang T. et al. Effect of sirolimus on liver cirrhosis and hepatic encephalopathy of common bile duct-ligated rats. Eur J Pharmacol. 2018; 824: 133–39.


https://doi.org/10.1016/j.ejphar.2018.02.016. PMID: 29444470.


80. Kwon M., Han J., Kim U.J. et al. Inhibition of mammalian target of rapamycin (mTOR) signaling in the insular cortex alleviates neuropathic pain after peripheral nerve injury. Front Mol Neurosci. 2017; 10: 79.


https://doi.org/10.3389/fnmol.2017.00079. PMID: 28377693. PMCID: PMC5359287.


81. Ma Y., Zhang G., Kuang Z. et al. Empagliflozin activates sestrin2-mediated AMPK/mTOR pathway and ameliorates lipid accumulation in obesity-related nonalcoholic fatty liver disease. Front Pharmacol. 2022; 13: 944886.


https://doi.org/10.3389/fphar.2022.944886. PMID: 36133815. PMCID: PMC9483033.


82. Zhou Y., Zhang Y., Botchway B.O.A. et al. Sestrin2 can alleviate endoplasmic reticulum stress to improve traumatic brain injury by activating AMPK/mTORC1 signaling pathway. Metab Brain Dis. 2024; 39(3): 439–52.


https://doi.org/10.1007/s11011-023-01323-2. PMID: 38047978.


83. Li Y., Zhang J., Zhou K. et al. Elevating sestrin2 attenuates endoplasmic reticulum stress and improves functional recovery through autophagy activation after spinal cord injury. Cell Biol Toxicol. 2021; 37(3): 401–19.


https://doi.org/10.1007/s10565-020-09550-4. PMID: 32740777.


84. Li Y., Wu J., Yu S. et al. Sestrin2 promotes angiogenesis to alleviate brain injury by activating Nrf2 through regulating the interaction between p62 and Keap1 following photothrombotic stroke in rats. Brain Res. 2020; 1745: 146948.


https://doi.org/10.1016/j.brainres.2020.146948. PMID: 32526292.


85. Yang Y., Ding H., Yang C. et al. Sestrin2 provides cerebral protection through activation of Nrf2 signaling in microglia following subarachnoid hemorrhage. Front Immunol. 2023; 14: 1089576.


https://doi.org/10.3389/fimmu.2023.1089576. PMID: 36761756. PMCID: PMC9903076.


86. Chen S.D., Yang J.L., Hsieh Y.H. et al. Potential roles of sestrin2 in Alzheimer’s disease: Antioxidation, autophagy promotion, and beyond. Biomedicines. 2021; 9(10): 1308.


https://doi.org/10.3390/biomedicines9101308. PMID: 34680426. PMCID: PMC8533411.


87. Kallenborn-Gerhardt W., Lu R., Syhr K.M. et al. Antioxidant activity of sestrin 2 controls neuropathic pain after peripheral nerve injury. Antioxid Redox Signal. 2013; 19(17): 2013–23.


https://doi.org/10.1089/ars.2012.4958. PMID: 23495831. PMCID: PMC3869453.


88. Takahara T., Amemiya Y., Sugiyama R. et al. Amino acid-dependent control of mTORC1 signaling: a variety of regulatory modes. J Biomed Sci. 2020; 27(1): 87.


https://doi.org/10.1186/s12929-020-00679-2. PMID: 32799865. PMCID: PMC7429791.


89. Ying Y., Jiang C., Zhang M. et al. Phloretin protects against cardiac damage and remodeling via restoring SIRT1 and anti-inflammatory effects in the streptozotocin-induced diabetic mouse model. Aging (Albany NY). 2019; 11(9): 2822–35.


https://doi.org/10.18632/aging.101954. PMID: 31076562. PMCID: PMC6535073.


90. Ghosh H.S., McBurney M., Robbins P.D. SIRT1 negatively regulates the mammalian target of rapamycin. PLoS One. 2010; 5(2): e9199.


https://doi.org/10.1371/journal.pone.0009199. PMID: 20169165. PMCID: PMC2821410.


91. Takashima M., Nakamura K., Kiyohara T. et al. Low-dose sodium-glucose cotransporter 2 inhibitor ameliorates ischemic brain injury in mice through pericyte protection without glucose-lowering effects. Commun Biol. 2022; 5(1): 653.


https://doi.org/10.1038/s42003-022-03605-4. PMID: 35780235. PMCID: PMC9250510.


92. Joosten L.A.B., Crişan T.O., Bjornstad P., Johnson R.J. Asymptomatic hyperuricaemia: a silent activator of the innate immune system. Nat Rev Rheumatol. 2020; 16(2): 75–86.


https://doi.org/10.1038/s41584-019-0334-3. PMID: 31822862. PMCID: PMC7075706.


93. Suijk D.L.S., van Baar M.J.B., van Bommel E.J.M. et al. SGLT2 inhibition and uric acid excretion in patients with type 2 diabetes and normal kidney function. Clin J Am Soc Nephrol. 2022; 17(5): 663–71.


https://doi.org/10.2215/CJN.11480821. PMID: 35322793. PMCID: PMC9269569.


94. Soria L.R., Brunetti-Pierri N. Ammonia and autophagy: An emerging relationship with implications for disorders with hyperammonemia. J Inherit Metab Dis. 2019; 42(6): 1097–1104.


https://doi.org/10.1002/jimd.12061. PMID: 30671986.


95. Davuluri G., Krokowski D., Guan B.J. et al. Metabolic adaptation of skeletal muscle to hyperammonemia drives the beneficial effects of l-leucine in cirrhosis. J Hepatol. 2016; 65(5): 929–37.


https://doi.org/10.1016/j.jhep.2016.06.004. PMID: 27318325. PMCID: PMC5069194.


96. Trendelenburg A.U., Meyer A., Rohner D. et al. Myostatin reduces Akt/TORC1/p70S6K signaling, inhibiting myoblast differentiation and myotube size. Am J Physiol Cell Physiol. 2009; 296(6): C1258–C1270.


https://doi.org/10.1152/ajpcell.00105.2009. PMID: 19357233.


97. Kang S.H., Yoon E.L. Sarcopenic obesity, the possible culprit for nonalcoholic fatty liver disease or fibrosis. Gut Liver. 2023; 17(1): 8–9.


https://doi.org/10.5009/gnl220543. PMID: 36636885. PMCID: PMC9840918.


98. Ehinger Y., Zhang Z., Phamluong K. et al. Brain-specific inhibition of mTORC1 eliminates side effects resulting from mTORC1 blockade in the periphery and reduces alcohol intake in mice. Nat Commun. 2021; 12(1): 4407.


https://doi.org/10.1038/s41467-021-24567-x. PMID: 34315870. PMCID: PMC8316332.


Об авторах / Для корреспонденции


Вероника Александровна Приходько, к. биол. н., старший преподаватель кафедры фармакологии и клинической фармакологии ФГБОУ ВО «Санкт-Петербургский государственный химико-фармацевтический университет» Минздрава России. Адрес: 197022, г. Санкт-Петербург, ул. Профессора Попова, д. 14, лит. А.
E-mail: veronika.prihodko@pharminnotech.com
ORCID: https://orcid.org/0000-0002-4690-1811
Сергей Владимирович Оковитый, д. м. н., профессор, заведующий кафедрой фармакологии и клинической фармакологии ФГБОУ ВО «Санкт-Петербургский государственный химико-фармацевтический университет» Минздрава России, профессор Научно-клинического и образовательного центра гастроэнтерологии и гепатологии ФГБОУ ВО «Санкт-Петербургский государственный университет». Адрес: 197022, г. Санкт-Петербург,
ул. Профессора Попова, д. 14, лит. А.
E-mail: sergey.okovity@pharminnotech.com
ORCID: https://orcid.org/0000-0003-4294-5531


Похожие статьи


Бионика Медиа