open access

Vol 82, No 3 (2023)
Original article
Submitted: 2022-02-09
Accepted: 2022-04-07
Published online: 2022-04-28
Get Citation

Protective effect of liriodendrin against liver ischaemia/reperfusion injury in mice via modulating oxidative stress, inflammation and nuclear factor kappa B/toll-like receptor 4 pathway

Z. Y. Yu1, G. Cheng234
·
Pubmed: 35607873
·
Folia Morphol 2023;82(3):668-676.
Affiliations
  1. Department of General Surgery, Panjin Central Hospital, Panjin, Liaoning Province, China
  2. Department of Intensive Care Unit, The People’s Hospital of Shimen County, Changde, Hunan Province, China
  3. Department of Clinical Medicine, Yiyang Medical College, Yiyang, Hunan Province, China
  4. Changsha Medical University, Changsha, Hunan Province, China

open access

Vol 82, No 3 (2023)
ORIGINAL ARTICLES
Submitted: 2022-02-09
Accepted: 2022-04-07
Published online: 2022-04-28

Abstract

Background: The aim of the present study was to investigate the protective effect
and mechanism of liriodendrin (LDN) is a lignan diglucoside in hepatic ischaemia/
/reperfusion (I/R) injury.
Materials and methods: The liver I/R was established in male C57BL/6 mice. The
effect of LDN is initially investigated on hepatic I/R injury via estimating histopathology
of liver. The level of metabolic enzymes alanine aminotransferase (ALT),
aspartate aminotransferase (AST) and alkaline phosphatase (ALP) was studied
along with apoptosis of mouse hepatocytes via TUNEL and flow cytometry analysis.
The effect of LDN was investigated on oxidative stress biomarkers (glutathione
[GSH] content, malondialdehyde [MDA] and superoxide dismutase [SOD] activities)
and pro-inflammatory cytokines (tumour necrosis factor alpha [TNF-α], interleukin
[IL]-1β and IL-6). Western blot study was also conducted to elucidate the effect
of LDN on toll-like receptor 4/nuclear factor kappa B (TLR4/NF-kB).
Results: Liriodendrin alleviates liver I/R injury, as manifested by decreased plasma
ALT, AST and ALP with improvement in liver necrotic area. LDN also reduces apoptosis
of mouse hepatocytes with reduction of oxidative stress and generation
of pro-inflammatory cytokines. It significantly reduces the expression of TLR4
and NF-kB.
Conclusions: The study demonstrated that LDN reduces liver injury and prevented
apoptosis of hepatocytes following I/R injury. In addition, LDN also reduces
oxidative stress, inflammation, and TLR4/NF-kB in I/R injured mice.

Abstract

Background: The aim of the present study was to investigate the protective effect
and mechanism of liriodendrin (LDN) is a lignan diglucoside in hepatic ischaemia/
/reperfusion (I/R) injury.
Materials and methods: The liver I/R was established in male C57BL/6 mice. The
effect of LDN is initially investigated on hepatic I/R injury via estimating histopathology
of liver. The level of metabolic enzymes alanine aminotransferase (ALT),
aspartate aminotransferase (AST) and alkaline phosphatase (ALP) was studied
along with apoptosis of mouse hepatocytes via TUNEL and flow cytometry analysis.
The effect of LDN was investigated on oxidative stress biomarkers (glutathione
[GSH] content, malondialdehyde [MDA] and superoxide dismutase [SOD] activities)
and pro-inflammatory cytokines (tumour necrosis factor alpha [TNF-α], interleukin
[IL]-1β and IL-6). Western blot study was also conducted to elucidate the effect
of LDN on toll-like receptor 4/nuclear factor kappa B (TLR4/NF-kB).
Results: Liriodendrin alleviates liver I/R injury, as manifested by decreased plasma
ALT, AST and ALP with improvement in liver necrotic area. LDN also reduces apoptosis
of mouse hepatocytes with reduction of oxidative stress and generation
of pro-inflammatory cytokines. It significantly reduces the expression of TLR4
and NF-kB.
Conclusions: The study demonstrated that LDN reduces liver injury and prevented
apoptosis of hepatocytes following I/R injury. In addition, LDN also reduces
oxidative stress, inflammation, and TLR4/NF-kB in I/R injured mice.

Get Citation

Keywords

liriodendrin, liver ischaemia/reperfusion injury, apoptosis, inflammation

About this article
Title

Protective effect of liriodendrin against liver ischaemia/reperfusion injury in mice via modulating oxidative stress, inflammation and nuclear factor kappa B/toll-like receptor 4 pathway

Journal

Folia Morphologica

Issue

Vol 82, No 3 (2023)

Article type

Original article

Pages

668-676

Published online

2022-04-28

Page views

1191

Article views/downloads

669

DOI

10.5603/FM.a2022.0049

Pubmed

35607873

Bibliographic record

Folia Morphol 2023;82(3):668-676.

Keywords

liriodendrin
liver ischaemia/reperfusion injury
apoptosis
inflammation

Authors

Z. Y. Yu
G. Cheng

References (40)
  1. Agrawal S, Dhiman RK, Limdi JK. Evaluation of abnormal liver function tests. Postgrad Med J. 2016; 92(1086): 223–234.
  2. Arumugam TV, Okun E, Tang SC, et al. Toll-like receptors in ischemia-reperfusion injury. Shock. 2009; 32(1): 4–16.
  3. Badrick T, Turner P. Review and recommendations for the component tests in the liver function test profile. Indian J Clin Biochem. 2016; 31(1): 21–29.
  4. Balunas MJ, Kinghorn AD. Drug discovery from medicinal plants. Life Sci. 2005; 78(5): 431–441.
  5. Bavarsad K, Riahi MM, Saadat S, et al. Protective effects of curcumin against ischemia-reperfusion injury in the liver. Pharmacol Res. 2019; 141: 53–62.
  6. Birben E, Sahiner UM, Sackesen C, et al. Oxidative stress and antioxidant defense. World Allergy Organ J. 2012; 5(1): 9–19.
  7. Czigány Z, Turóczi Z, Bulhardt O, et al. [Remote ischemic conditioning: short-term effects on rat liver ischemic-reperfusion injury]. Orv Hetil. 2012; 153(40): 1579–1587.
  8. Datta G, Fuller BJ, Davidson BR. Molecular mechanisms of liver ischemia reperfusion injury: insights from transgenic knockout models. World J Gastroenterol. 2013; 19(11): 1683–1698.
  9. Feng C, Li BG, Gao XP, et al. A new triterpene and an antiarrhythmic liriodendrin from Pittosporum brevicalyx. Arch Pharm Res. 2010; 33(12): 1927–1932.
  10. Gan M, Zhang Y, Lin S, et al. Glycosides from the root of Iodes cirrhosa. J Nat Prod. 2008; 71(4): 647–654.
  11. Gong J, Xue L, Wei M, et al. Liriodendrin alleviates sciatic endometriosis-associated pain in rats via suppressing inflammatory response and regulating the signaling pathway of Pl3K/Akt/mToR. Arch Med Sci. 2021.
  12. Han SJ, Lee HT. Mechanisms and therapeutic targets of ischemic acute kidney injury. Kidney Res Clin Pract. 2019; 38(4): 427–440.
  13. Jung HJ, Park HJ, Kim RG, et al. In vivo anti-inflammatory and antinociceptive effects of liriodendrin isolated from the stem bark of Acanthopanax senticosus. Planta Med. 2003; 69(7): 610–616.
  14. Kudoh K, Uchinami H, Yoshioka M, et al. Nrf2 activation protects the liver from ischemia/reperfusion injury in mice. Ann Surg. 2014; 260(1): 118–127.
  15. Li J, Li RJ, Lv GY, et al. The mechanisms and strategies to protect from hepatic ischemia-reperfusion injury. Eur Rev Med Pharmacol Sci. 2015; 19(11): 2036–2047.
  16. Li S, Qin Q, Luo D, et al. Hesperidin ameliorates liver ischemia/reperfusion injury via activation of the Akt pathway. Mol Med Rep. 2020; 22(6): 4519–4530.
  17. Li Y, Tong L, Zhang J, et al. Galangin alleviates liver ischemia-reperfusion injury in a rat model by mediating the PI3K/AKT pathway. Cell Physiol Biochem. 2018; 51(3): 1354–1363.
  18. Ligeret H, Brault A, Vallerand D, et al. Antioxidant and mitochondrial protective effects of silibinin in cold preservation-warm reperfusion liver injury. J Ethnopharmacol. 2008; 115(3): 507–514.
  19. Lin J, Huang HF, Yang SK, et al. The effect of Ginsenoside Rg1 in hepatic ischemia reperfusion (I/R) injury ameliorates ischemia-reperfusion-induced liver injury by inhibiting apoptosis. Biomed Pharmacother. 2020; 129: 110398.
  20. Liu H, Fan J, Zhang W, et al. OTUD4 alleviates hepatic ischemia-reperfusion injury by suppressing the K63-linked ubiquitination of TRAF6. Biochem Biophys Res Commun. 2020; 523(4): 924–930.
  21. Masih A, Agnihotri AK, Srivastava JK, et al. Discovery of novel pyrazole derivatives as a potent anti-inflammatory agent in RAW264.7 cells via inhibition of NF-ĸB for possible benefit against SARS-CoV-2. J Biochem Mol Toxicol. 2021; 35(3): e22656.
  22. Nam JW, Kim SY, Yoon T, et al. Heat shock factor 1 inducers from the bark of Eucommia ulmoides as cytoprotective agents. Chem Biodivers. 2013; 10(7): 1322–1327.
  23. Neumann M, Naumann M. Beyond IkappaBs: alternative regulation of NF-kappaB activity. FASEB J. 2007; 21(11): 2642–2654.
  24. Pan Y, Yu S, Wang J, et al. N-acetyl-L-tryptophan attenuates hepatic ischemia-reperfusion injury via regulating TLR4/NLRP3 signaling pathway in rats. PeerJ. 2021; 9: e11909.
  25. Rampes S, Ma D. Hepatic ischemia-reperfusion injury in liver transplant setting: mechanisms and protective strategies. J Biomed Res. 2019; 33(4): 221–234.
  26. Ran XK, Wang XT, Liu PP, et al. Cytotoxic constituents from the leaves of Broussonetia papyrifera. Chin J Nat Med. 2013; 11(3): 269–273.
  27. U PR, M MU, Videla L. Mecanismos moleculares en el daño por isquemia-reperfusión hepática y en el preacondicionamiento isquémico. Revista Médica de Chile. 2005; 133(4).
  28. Srivastava J, Awatade N, Bhat H, et al. Pharmacological evaluation of hybrid thiazolidin-4-one-1,3,5-triazines for NF-κB, biofilm and CFTR activity. RSC Advances. 2015; 5(108): 88710–88718.
  29. Storz G, Imlay JA. Oxidative stress. Curr Opin Microbiol. 1999; 2(2): 188–194.
  30. Tüfek A, Tokgöz O, Aliosmanoglu I, et al. The protective effects of dexmedetomidine on the liver and remote organs against hepatic ischemia reperfusion injury in rats. Int J Surg. 2013; 11(1): 96–100.
  31. Wang J, Yu S, Li J, et al. Protective role of -acetyl-l-tryptophan against hepatic ischemia-reperfusion injury via the RIP2/caspase-1/IL-1β signaling pathway. Pharm Biol. 2019; 57(1): 385–391.
  32. Wang M, Zhang Ji, Zhang J, et al. Methyl eugenol attenuates liver ischemia reperfusion injury via activating PI3K/Akt signaling. Int Immunopharmacol. 2021; 99: 108023.
  33. Wang S, Hu Y, Liu T. Plant distribution and pharmacological activity of flavonoids. Trad Med Res. 2019; 4(5): 269–287.
  34. Wu QR. Wang YG. Apoptosis and ischemia-reperfusion injury following liver transplantation. J Clin Rehab Tissue Eng Res. 2011; 15(18): 3371–3375.
  35. Xue S, He W, Zeng X, et al. Hypothermic machine perfusion attenuates ischemia/reperfusion injury against rat livers donated after cardiac death by activating the Keap1/Nrf2‑ARE signaling pathway. Mol Med Rep. 2018; 18(1): 815–826.
  36. Yang G, Yang Yu, Li Y, et al. Remote liver ischaemic preconditioning protects rat brain against cerebral ischaemia-reperfusion injury by activation of an AKT-dependent pathway. Exp Physiol. 2020; 105(5): 852–863.
  37. Yang Y, Tang Z, Wei Y. Hypoglycemic effects of active constituents extracted from the stem bark of Kalopanax septemlobus (Thunb.) Koidz. in Guangxi. Med J Wuhan Uni. 2008; 29(6): 759–762.
  38. Yang Yi, Wang P, Zhang C, et al. Hepatocyte-derived MANF alleviates hepatic ischaemia-reperfusion injury via regulating endoplasmic reticulum stress-induced apoptosis in mice. Liver Int. 2021; 41(3): 623–639.
  39. Yoon SY, Kim CY, Han HJ, et al. Protective effect of ischemic postconditioning against hepatic ischemic reperfusion injury in rat liver. Ann Surg Treat Res. 2015; 88(5): 241–245.
  40. Yu Q, Chen S, Tang H, et al. Veratric acid alleviates liver ischemia/reperfusion injury by activating the Nrf2 signaling pathway. Int Immunopharmacol. 2021; 101(Pt B): 108294.

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By VM Media Group sp. z o.o., Grupa Via Medica, Świętokrzyska 73, 80–180 Gdańsk, Poland

tel.: +48 58 320 94 94, faks: +48 58 320 94 60, e-mail: viamedica@viamedica.pl