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Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Research Article

Albiflorin Alleviates Sepsis-induced Acute Liver Injury through mTOR/p70S6K Pathway

Author(s): Yanan Liu, Lizhi Feng and Lan Yao*

Volume 24, Issue 3, 2024

Published on: 10 May, 2023

Page: [344 - 354] Pages: 11

DOI: 10.2174/1566524023666230309124004

Price: $65

Abstract

Background: Sepsis often induces hepatic dysfunction and inflammation, accounting for a significant increase in the incidence and mortality rates. To this end, albiflorin (AF) has garnered enormous interest due to its potent anti-inflammatory activity. However, the substantial effect of AF on sepsis-mediated acute liver injury (ALI), along with its potential mechanism of action, remains to be explored.

Methods: An LPS-mediated primary hepatocyte injury cell model in vitro and a mouse model of CLP-mediated sepsis in vivo were initially built to explore the effect of AF on sepsis. Furthermore, the hepatocyte proliferation by CCK-8 assay in vitro and animal survival analyses in vivo for the survival time of mice were carried out to determine an appropriate concentration of AF. Then, flow cytometry, Western blot (WB), and TUNEL staining analyses were performed to investigate the effect of AF on the apoptosis of hepatocytes. Moreover, the expressions of various inflammatory factors by ELISA and RT-qPCR analyses and oxidative stress by ROS, MDA, and SOD assays were determined. Finally, the potential mechanism of AF alleviating the sepsis-mediated ALI via the mTOR/p70S6K pathway was explored through WB analysis.

Results: AF treatment showed a significant increase in the viability of LPS-inhibited mouse primary hepatocytes cells. Moreover, the animal survival analyses of the CLP model mice group indicated a shorter survival time than the CLP+AF group. AF-treated groups showed significantly decreased hepatocyte apoptosis, inflammatory factors, and oxidative stress. Finally, AF exerted an effect by suppressing the mTOR/p70S6K pathway.

Conclusion: In summary, these findings demonstrated that AF could effectively alleviate sepsis-mediated ALI via the mTOR/p70S6K signaling pathway.

[1]
Cecconi M, Evans L, Levy M, Rhodes A. Sepsis and septic shock. Lancet 2018; 392(10141): 75-87.
[http://dx.doi.org/10.1016/S0140-6736(18)30696-2] [PMID: 29937192]
[2]
Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016; 315(8): 801-10.
[http://dx.doi.org/10.1001/jama.2016.0287] [PMID: 26903338]
[3]
Strnad P, Tacke F, Koch A, Trautwein C. Liver-guardian, modifier and target of sepsis. Nat Rev Gastroenterol Hepatol 2017; 14(1): 55-66.
[http://dx.doi.org/10.1038/nrgastro.2016.168] [PMID: 27924081]
[4]
Lelubre C, Vincent JL. Mechanisms and treatment of organ failure in sepsis. Nat Rev Nephrol 2018; 14(7): 417-27.
[http://dx.doi.org/10.1038/s41581-018-0005-7] [PMID: 29691495]
[5]
Trefts E, Gannon M, Wasserman DH. The liver. Curr Biol 2017; 27(21): R1147-51.
[http://dx.doi.org/10.1016/j.cub.2017.09.019] [PMID: 29112863]
[6]
Coutinho-Silva R, Morandini AC, Savio LEB. The role of p2x7 receptor in infectious inflammatory diseases and the influence of ectonucleotidases. Biomed J 2014; 37(4): 169-77.
[http://dx.doi.org/10.4103/2319-4170.127803] [PMID: 25116711]
[7]
Samarghandian S, Azimi-Nezhad M, Farkhondeh T, Samini F. Anti-oxidative effects of curcumin on immobilization-induced oxidative stress in rat brain, liver and kidney. Biomed Pharmacother 2017; 87: 223-9.
[http://dx.doi.org/10.1016/j.biopha.2016.12.105] [PMID: 28061405]
[8]
Savio LEB, de Andrade Mello P, Figliuolo VR, et al. CD39 limits P2X7 receptor inflammatory signaling and attenuates sepsis-induced liver injury. J Hepatol 2017; 67(4): 716-26.
[http://dx.doi.org/10.1016/j.jhep.2017.05.021] [PMID: 28554875]
[9]
Xu S, Li L, Wu J, et al. Melatonin attenuates sepsis-induced small-intestine injury by upregulating SIRT3-mediated oxidative-stress inhibition, mitochondrial protection, and autophagy induction. Front Immunol 2021; 12: 625627.
[http://dx.doi.org/10.3389/fimmu.2021.625627] [PMID: 33790896]
[10]
Kim TS, Choi DH. Liver dysfunction in sepsis. Korean J Gastroenterol 2020; 75(4): 182-7.
[http://dx.doi.org/10.4166/kjg.2020.75.4.182] [PMID: 32326684]
[11]
He DY, Dai SM. Anti-inflammatory and immunomodulatory effects of paeonia lactiflora pall., a traditional chinese herbal medicine. Front Pharmacol 2011; 2: 10.
[http://dx.doi.org/10.3389/fphar.2011.00010] [PMID: 21687505]
[12]
Ma X, Song M, Yan Y, et al. Albiflorin alleviates cognitive dysfunction in STZ-induced rats. Aging 2021; 13(14): 18287-97.
[http://dx.doi.org/10.18632/aging.203274] [PMID: 34319254]
[13]
Ruan Y, Ling J, Ye F, et al. Paeoniflorin alleviates CFAinduced inflammatory pain by inhibiting TRPV1 and succinate/ SUCNR1-HIF-1alpha/NLPR3 pathway. Int Immunopharmacol 2021; 101(Pt B): 108364.
[14]
Liu B, Meng X, Ma Y, et al. Clinical safety of total glucosides of paeony adjuvant therapy for rheumatoid arthritis treatment: A systematic review and meta-analysis. BMC Complement Med Ther 2021; 21(1): 102.
[http://dx.doi.org/10.1186/s12906-021-03252-y]
[15]
Zeng XY, Zhou X, Xu J, et al. Screening for the efficacy on lipid accumulation in 3T3-L1 cells is an effective tool for the identification of new anti-diabetic compounds. Biochem Pharmacol 2012; 84(6): 830-7.
[http://dx.doi.org/10.1016/j.bcp.2012.07.003] [PMID: 22820245]
[16]
Liu P, Chen J, Ma S, Zhang J, Zhou J. Albiflorin attenuates mood disorders under neuropathic pain state by suppressing the hippocampal NLRP3 inflammasome activation during chronic constriction injury. Int J Neuropsychopharmacol 2021; 24(1): 64-76.
[http://dx.doi.org/10.1093/ijnp/pyaa076] [PMID: 33000169]
[17]
Pei L, He L. Hepatoprotective effect of anemoside B4 against sepsis-induced acute liver injury through modulating the mTOR/p70S6K-mediated autophagy. Chem Biol Interact 2021; 345: 109534.
[http://dx.doi.org/10.1016/j.cbi.2021.109534] [PMID: 34051206]
[18]
Jeong MY, Park J, Youn DH, et al. Albiflorin ameliorates obesity by inducing thermogenic genes via AMPK and PI3K/AKT in vivo and in vitro. Metabolism 2017; 73: 85-99.
[http://dx.doi.org/10.1016/j.metabol.2017.05.009] [PMID: 28732574]
[19]
Wang L, Cheng L, Ma L, et al. Alnustone inhibits the growth of hepatocellular carcinoma via ROS ‐ mediated PI3K /Akt/mTOR/ p70S6K axis. Phytother Res 2022; 36(1): 525-42.
[http://dx.doi.org/10.1002/ptr.7337] [PMID: 34847624]
[20]
Dai Y, Chen Y, Wei G, Zha L, Li X. Ivabradine protects rats against myocardial infarction through reinforcing autophagy via inhibiting PI3K/AKT/mTOR/p70S6K pathway. Bioengineered 2021; 12(1): 1826-37.
[http://dx.doi.org/10.1080/21655979.2021.1925008] [PMID: 33975512]
[21]
Jiang Z, Bo L, Meng Y, et al. Overexpression of homeodomain-interacting protein kinase 2 (HIPK2) attenuates sepsis-mediated liver injury by restoring autophagy. Cell Death Dis 2018; 9(9): 847.
[http://dx.doi.org/10.1038/s41419-018-0838-9] [PMID: 30154452]
[22]
Rittirsch D, Huber-Lang MS, Flierl MA, Ward PA. Immunodesign of experimental sepsis by cecal ligation and puncture. Nat Protoc 2009; 4(1): 31-6.
[http://dx.doi.org/10.1038/nprot.2008.214] [PMID: 19131954]
[23]
Possamai LA, Thursz MR, Wendon JA, Antoniades CG. Modulation of monocyte/macrophage function: A therapeutic strategy in the treatment of acute liver failure. J Hepatol 2014; 61(2): 439-45.
[http://dx.doi.org/10.1016/j.jhep.2014.03.031] [PMID: 24703954]
[24]
Jun P, Rahmat E, Han CH, Yang C, Kang Y. Traditional chinese medicine and traditional indonesian medicine: A comparative review of herbal medicines restricted in pregnancy. Chin J Integr Med 2021; 27(10): 794-800.
[http://dx.doi.org/10.1007/s11655-021-3487-7] [PMID: 34241802]
[25]
Antoniades CG, Khamri W, Abeles RD, et al. Secretory leukocyte protease inhibitor: A pivotal mediator of anti-inflammatory responses in acetaminophen-induced acute liver failure. Hepatology 2014; 59(4): 1564-76.
[http://dx.doi.org/10.1002/hep.26933] [PMID: 24282114]
[26]
Pang GM, Li FX, Yan Y, et al. Herbal medicine in the treatment of patients with type 2 diabetes mellitus. Chin Med J 2019; 132(1): 78-85.
[http://dx.doi.org/10.1097/CM9.0000000000000006] [PMID: 30628962]
[27]
Zhang L, Wei W. Anti-inflammatory and immunoregulatory effects of paeoniflorin and total glucosides of paeony. Pharmacol Ther 2020; 207: 107452.
[http://dx.doi.org/10.1016/j.pharmthera.2019.107452] [PMID: 31836457]
[28]
Zhao ZX, Fu J, Ma SR, et al. Gut-brain axis metabolic pathway regulates antidepressant efficacy of albiflorin. Theranostics 2018; 8(21): 5945-59.
[http://dx.doi.org/10.7150/thno.28068] [PMID: 30613273]
[29]
Wang YS, Shen CY, Jiang JG. Antidepressant active ingredients from herbs and nutraceuticals used in TCM: Pharmacological mechanisms and prospects for drug discovery. Pharmacol Res 2019; 150: 104520.
[http://dx.doi.org/10.1016/j.phrs.2019.104520] [PMID: 31706012]
[30]
Mayr FB, Yende S, Angus DC. Epidemiology of severe sepsis. Virulence 2014; 5(1): 4-11.
[http://dx.doi.org/10.4161/viru.27372] [PMID: 24335434]
[31]
Liu X, Yang X, Han L, et al. Pterostilbene alleviates polymicrobial sepsis-induced liver injury: Possible role of SIRT1 signaling. Int Immunopharmacol 2017; 49: 50-9.
[http://dx.doi.org/10.1016/j.intimp.2017.05.022] [PMID: 28550734]
[32]
Jhanwar-Uniyal M, Wainwright JV, Mohan AL, et al. Diverse signaling mechanisms of mTOR complexes: mTORC1 and mTORC2 in forming a formidable relationship. Adv Biol Regul 2019; 72: 51-62.
[http://dx.doi.org/10.1016/j.jbior.2019.03.003] [PMID: 31010692]
[33]
Newton PT, Vuppalapati KK, Bouderlique T, Chagin AS. Pharmacological inhibition of lysosomes activates the MTORC1 signaling pathway in chondrocytes in an autophagy-independent manner. Autophagy 2015; 11(9): 1594-607.
[http://dx.doi.org/10.1080/15548627.2015.1068489] [PMID: 26259639]

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