Abstract
Lung injury associated with systemic inflammatory response is a common problem affecting human health. Previous studies have shown that lycorine exerts a anti-inflammatory effect. However, whether lycorine alleviates lung injury remains unclear. To explore this issue, BALB/c mice and MLE-12 cells were treated with lipopolysaccharide (LPS) to establish lung injury mouse model and cell model, respectively. Glycyrrhizic acid, known as an inhibitor of ALI, was also used to study the effects of lycorine in vitro. Our results showed that after LPS treatment, the lung injury score, lung wet-to-dry weight ratio, and malondialdehyde (MDA) production in the lung tissues and the expression levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in bronchoalveolar lavage fluid were significantly increased, whereas their levels were decreased by lycorine. Additionally, LPS injection activated the high-mobility group box 1 (HMGB1)/Toll-like receptors (TLRs)/NF-κB pathway. However, lycorine treatment attenuated the activity of the HMGB1/TLRs/NF-κB pathway in the lung tissues. In vitro studies showed that lycorine administration significantly decreased the levels of inflammatory cytokines and MDA and attenuated the activity of the HMGB1/TLRs/NF-κB pathway in LPS-treated cells. Moreover, the inhibitory effects of lycorine on the inflammatory response and oxidative stress in LPS-treated lung cells were similar with that of glycyrrhizic acid, and this inhibition was intensified by both lycorine and glycyrrhizic acid treatment. We suggest that lycorine could alleviate LPS-induced lung injury of inflammation and oxidative stress by blocking the HMGB1/TLRs/NF-κB pathway, which gives a new perspective for ALI therapy to treat lycorine as a potential treatment clinically.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Explore related subjects
Discover the latest articles and news from researchers in related subjects, suggested using machine learning.References
Bi J, Cui R, Li Z, Liu C, Zhang J (2017) Astaxanthin alleviated acute lung injury by inhibiting oxidative/nitrative stress and the inflammatory response in mice. Biomed Pharmacother 95:974–982. https://doi.org/10.1016/j.biopha.2017.09.012
Bouros D et al (2004) The clinical significance of serum and bronchoalveolar lavage inflammatory cytokines in patients at risk for Acute Respiratory Distress Syndrome. BMC Pulm Med 4:6. https://doi.org/10.1186/1471-2466-4-6
Butt Y, Kurdowska A, Allen TC (2016) Acute lung injury: a clinical and molecular review. Arch Pathol Lab Med 140:345–350. https://doi.org/10.5858/arpa.2015-0519-RA
Citoglu GS, Acikara OB, Yilmaz BS, Ozbek H (2012) Evaluation of analgesic, anti-inflammatory and hepatoprotective effects of lycorine from Sternbergia fisheriana (Herbert) Rupr. Fitoterapia 83:81–87. https://doi.org/10.1016/j.fitote.2011.09.008
Crapo JD (2003) Oxidative stress as an initiator of cytokine release and cell damage. Eur Respir J Suppl 44:4s–6s. https://doi.org/10.1183/09031936.03.00000203a
Deng G et al (2017) Lianqinjiedu decoction attenuates LPS-induced inflammation and acute lung injury in rats via TLR4/NF-kappaB pathway. Biomed Pharmacother 96:148–152. https://doi.org/10.1016/j.biopha.2017.09.094
Di Candia L et al (2017) HMGB1 is upregulated in the airways in asthma and potentiates airway smooth muscle contraction via TLR4. J Allergy Clin Immunol 140:584 e588–587 e588. https://doi.org/10.1016/j.jaci.2016.11.049
Dong Z, Yuan Y (2018) Accelerated inflammation and oxidative stress induced by LPS in acute lung injury: iotanhibition by ST1926. Int J Mol Med 41:3405–3421. https://doi.org/10.3892/ijmm.2018.3574
Fan E, Brodie D, Slutsky AS (2018) Acute respiratory distress syndrome: advances in diagnosis and treatment. JAMA 319:698–710. https://doi.org/10.1001/jama.2017.21907
Fan EKY, Fan J (2018) Regulation of alveolar macrophage death in acute lung inflammation. Respir Res 19:50. https://doi.org/10.1186/s12931-018-0756-5
Gao F, Chen R, Xi Y, Zhao Q, Gao H (2019) Long noncoding RNA MALAT1 regulates sepsis in patients with burns by modulating miR214 with TLR5. Mol Med Rep 19:3756–3766. https://doi.org/10.3892/mmr.2019.10028
Ghosh S, Hayden MS (2008) New regulators of NF-kappaB in inflammation. Nat Rev Immunol 8:837–848. https://doi.org/10.1038/nri2423
Giridharan S, Srinivasan M (2018) Mechanisms of NF-kappaB p65 and strategies for therapeutic manipulation. J Inflamm Res 11:407–419. https://doi.org/10.2147/JIR.S140188
Guo RF, Ward PA (2007) Role of oxidants in lung injury during sepsis. Antioxid Redox Signal 9:1991–2002. https://doi.org/10.1089/ars.2007.1785
Guo Y et al (2016) A conserved inhibitory mechanism of a lycorine derivative against enterovirus and hepatitis C virus. Antimicrob Agents Chemother 60:913–924. https://doi.org/10.1128/AAC.02274-15
Han X, Wu YC, Meng M, Sun QS, Gao SM, Sun H (2018) Linarin prevents LPSinduced acute lung injury by suppressing oxidative stress and inflammation via inhibition of TXNIP/NLRP3 and NFkappaB pathways. Int J Mol Med 42:1460–1472. https://doi.org/10.3892/ijmm.2018.3710
Herold S, Gabrielli NM, Vadasz I (2013) Novel concepts of acute lung injury and alveolar-capillary barrier dysfunction. Am J Physiol Lung Cell Mol Physiol 305:L665–681. https://doi.org/10.1152/ajplung.00232.2013
Ito H et al (2019) Role of TLR5 in inflammation and tissue damage after intestinal ischemia-reperfusion injury. Biochem Biophys Res Commun 519:15–22. https://doi.org/10.1016/j.bbrc.2019.08.083
Jiang W et al (2016) The protective effect of Trillin LPS-induced acute lung injury by the regulations of inflammation and oxidative state. Chem Biol Interact 243:127–134. https://doi.org/10.1016/j.cbi.2015.09.010
Kang J et al (2012) Lycorine inhibits lipopolysaccharide-induced iNOS and COX-2 up-regulation in RAW264.7 cells through suppressing P38 and STATs activation and increases the survival rate of mice after LPS challenge. Int immunopharmacol 12:249–256. https://doi.org/10.1016/j.intimp.2011.11.018
Lei J, Wei Y, Song P, Li Y, Zhang T, Feng Q, Xu G (2018) Cordycepin inhibits LPS-induced acute lung injury by inhibiting inflammation and oxidative stress. Eur J Pharmacol 818:110–114. https://doi.org/10.1016/j.ejphar.2017.10.029
Meduri GU, Headley S, Kohler G, Stentz F, Tolley E, Umberger R, Leeper K (1995) Persistent elevation of inflammatory cytokines predicts a poor outcome in ARDS. Plasma IL-1 beta and IL-6 levels are consistent and efficient predictors of outcome over time. Chest 107:1062–1073. https://doi.org/10.1378/chest.107.4.1062
Meng L et al (2018) The protective effect of dexmedetomidine on LPS-induced acute lung injury through the HMGB1-mediated TLR4/NF-kappaB and PI3K/Akt/mTOR pathways. Mol Immunol 94:7–17. https://doi.org/10.1016/j.molimm.2017.12.008
Nair JJ, van Staden J (2019) Antiplasmodial lycorane alkaloid principles of the plant family amaryllidaceae. Planta Med 85:637–647. https://doi.org/10.1055/a-0880-5414
Park HJ, Gholam-Zadeh M, Suh JH, Choi HS (2019) Lycorine attenuates autophagy in osteoclasts via an axis of mROS/TRPML1/TFEB to Reduce LPS-induced bone loss. Oxid Med Cell Longev 2019:8982147. https://doi.org/10.1155/2019/8982147
Park WY et al (2001) Cytokine balance in the lungs of patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 164:1896–1903. https://doi.org/10.1164/ajrccm.164.10.2104013
Qu L et al (2019a) High-mobility group box 1 (HMGB1) and autophagy in acute lung injury (ALI): a review. Med Sci Monit 25:1828–1837. https://doi.org/10.12659/MSM.912867
Qu L et al (2019b) Glycyrrhizic acid ameliorates LPS-induced acute lung injury by regulating autophagy through the PI3K/AKT/mTOR pathway. Am J Transl Res 11:2042–2055
Rahman I, Marwick J, Kirkham P (2004) Redox modulation of chromatin remodeling: impact on histone acetylation and deacetylation NF-kappaB and pro-inflammatory gene expression. Biochem Pharmacol 68:1255–1267. https://doi.org/10.1016/j.bcp.2004.05.042
Roy M et al (2016) Lycorine downregulates HMGB1 to inhibit autophagy and enhances bortezomib activity in multiple myeloma. Theranostics 6:2209–2224. https://doi.org/10.7150/thno.15584
Toba H et al (2016) XB130 deficiency enhances lipopolysaccharide-induced septic response and acute lung injury. Oncotarget 7:25420–25431. https://doi.org/10.18632/oncotarget.8326
Wang G et al (2018) Lycorine suppresses endplate-chondrocyte degeneration and prevents intervertebral disc degeneration by inhibiting NF-kappaB signalling pathway. Cell Physiol Biochem 45:1252–1269. https://doi.org/10.1159/000487457
Winterbourn CC, Buss IH, Chan TP, Plank LD, Clark MA, Windsor JA (2000) Protein carbonyl measurements show evidence of early oxidative stress in critically ill patients. Crit Care Med 28:143–149. https://doi.org/10.1097/00003246-200001000-00024
Yan J, Shen S, He Y, Li Z (2019) TLR5 silencing reduced hyperammonaemia-induced liver injury by inhibiting oxidative stress and inflammation responses via inactivating NF-kappaB and MAPK signals. Chem Biol Interact 299:102–110. https://doi.org/10.1016/j.cbi.2018.11.026
Yang R, Yuan BC, Ma YS, Zhou S, Liu Y (2017) The anti-inflammatory activity of licorice, a widely used Chinese herb. Pharm Biol 55:5–18. https://doi.org/10.1080/13880209.2016.1225775
Ying X, Huang A, Xing Y, Lan L, Yi Z, He P (2017) Lycorine inhibits breast cancer growth and metastasis via inducing apoptosis and blocking Src/FAK-involved pathway. Sci China Life Sci 60:417–428. https://doi.org/10.1007/s11427-016-0368-y
Zhang ZM, Wang YC, Chen L, Li Z (2019) Protective effects of the suppressed NF-kappaB/TLR4 signaling pathway on oxidative stress of lung tissue in rat with acute lung injury. Kaohsiung J Med Sci 35:265–276. https://doi.org/10.1002/kjm2.12065
Zhao H, Zhao M, Wang Y, Li F, Zhang Z (2016) Glycyrrhizic acid prevents sepsis-induced acute lung injury and mortality in rats. J Histochem Cytochem 64:125–137. https://doi.org/10.1369/0022155415610168
Acknowledgements
This study was supported by grants from the National Natural Scientific Foundation of China (no. 81772045).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflicts of interest.
Ethics approval
All animal experiments were performed according to the National Institutes of Health guide for the care and use of laboratory animals and with the approval of the ethic committee of Harbin Medical University.
Rights and permissions
About this article
Cite this article
Ge, X., Meng, X., Fei, D. et al. Lycorine attenuates lipopolysaccharide-induced acute lung injury through the HMGB1/TLRs/NF-κB pathway. 3 Biotech 10, 369 (2020). https://doi.org/10.1007/s13205-020-02364-5
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s13205-020-02364-5