Glycyrrhizic Acid Ameliorates LPS-induced Acute Lung Injury by Regulating Autophagy Through the PI3K/AKT/mTOR Pathway

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2019 May 21

PMID 31105816

Citations 53

Authors

Lihua Qu

Chao Chen

Wei He

Yangye Chen

Yi Li

Yi Wen

Sichun Zhou

Yiqun Jiang

Xiaoping Yang

Ran Zhang

Li Shen

Affiliations

Soon will be listed here.

Abstract

Acute lung injury (ALI) is a major pathological issue characterized by serious inflammatory response, and a major clinically critical illness with high morbidity and mortality. Glycyrrhizic acid (GA) is a major bioactive constituent isolated from traditional Chinese herb licorice, which has been reported to have positive effects on inflammation. Nevertheless, the effects of GA on lipopolysaccharide (LPS)-treated ALI in mice have not been reported. The purpose of our study is to investigate the inhibitory effects of GA on ALI treated by LPS and to elucidate its possible mechanisms. We found that GA significantly attenuated lung injury and decreased the production of inflammatory factors TNF-α, IL-1β, and HMGB1 with LPS treatment. GA induced autophagy which was showed by enhanced number of autophagosomes through upregulating the protein levels of LC3-II/I and Beclin-1 and downregulating SQSTM1/P62. Moreover, pre-treatment of 3-Methyladenine (3-MA), an autophagy inhibitor, reversed the inhibiting effects of GA on the secretion of inflammatory factors in ALI. The PI3K/AKT/mTOR pathway was associated with GA-induced autophagy under ALI induced by LPS. In conclusion, this study indicated that GA inhibited the production of inflammatory factors in LPS-induced ALI by regulating the PI3K/AKT/mTOR pathway related autophagy, which may provide a novel therapeutic perspective of GA in ameliorating ALI.

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References

Atabai K, Matthay M . The pulmonary physician in critical care. 5: Acute lung injury and the acute respiratory distress syndrome: definitions and epidemiology. Thorax. 2002; 57(5):452-8. PMC: 1746331. DOI: 10.1136/thorax.57.5.452. View

Mizushima N, Levine B, Cuervo A, Klionsky D . Autophagy fights disease through cellular self-digestion. Nature. 2008; 451(7182):1069-75. PMC: 2670399. DOI: 10.1038/nature06639. View

Menegazzi M, Di Paola R, Mazzon E, Genovese T, Crisafulli C, Dal Bosco M . Glycyrrhizin attenuates the development of carrageenan-induced lung injury in mice. Pharmacol Res. 2008; 58(1):22-31. DOI: 10.1016/j.phrs.2008.05.012. View

Saitoh T, Fujita N, Jang M, Uematsu S, Yang B, Satoh T . Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production. Nature. 2008; 456(7219):264-8. DOI: 10.1038/nature07383. View

Yang Z, Klionsky D . Mammalian autophagy: core molecular machinery and signaling regulation. Curr Opin Cell Biol. 2009; 22(2):124-31. PMC: 2854249. DOI: 10.1016/j.ceb.2009.11.014. View

Scherz-Shouval R, Elazar Z . Regulation of autophagy by ROS: physiology and pathology. Trends Biochem Sci. 2010; 36(1):30-8. DOI: 10.1016/j.tibs.2010.07.007. View

Tang D, Loze M, Zeh H, Kang R . The redox protein HMGB1 regulates cell death and survival in cancer treatment. Autophagy. 2010; 6(8):1181-3. DOI: 10.4161/auto.6.8.13367. View

Kang R, Livesey K, Zeh H, Loze M, Tang D . HMGB1: a novel Beclin 1-binding protein active in autophagy. Autophagy. 2010; 6(8):1209-11. DOI: 10.4161/auto.6.8.13651. View

Zhou R, Yazdi A, Menu P, Tschopp J . A role for mitochondria in NLRP3 inflammasome activation. Nature. 2010; 469(7329):221-5. DOI: 10.1038/nature09663. View

10.

Nakahira K, Haspel J, Rathinam V, Lee S, Dolinay T, Lam H . Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat Immunol. 2010; 12(3):222-30. PMC: 3079381. DOI: 10.1038/ni.1980. View

11.

Harris J, Hartman M, Roche C, Zeng S, OShea A, Sharp F . Autophagy controls IL-1beta secretion by targeting pro-IL-1beta for degradation. J Biol Chem. 2011; 286(11):9587-97. PMC: 3058966. DOI: 10.1074/jbc.M110.202911. View

12.

Muller C, Salvayre R, Negre-Salvayre A, Vindis C . Oxidized LDLs trigger endoplasmic reticulum stress and autophagy: prevention by HDLs. Autophagy. 2011; 7(5):541-3. DOI: 10.4161/auto.7.5.15003. View

13.

Cross L, Matthay M . Biomarkers in acute lung injury: insights into the pathogenesis of acute lung injury. Crit Care Clin. 2011; 27(2):355-77. PMC: 3073651. DOI: 10.1016/j.ccc.2010.12.005. View

14.

Harris J . Autophagy and cytokines. Cytokine. 2011; 56(2):140-4. DOI: 10.1016/j.cyto.2011.08.022. View

15.

Tanaka A, Jin Y, Lee S, Zhang M, Kim H, Stolz D . Hyperoxia-induced LC3B interacts with the Fas apoptotic pathway in epithelial cell death. Am J Respir Cell Mol Biol. 2011; 46(4):507-14. PMC: 3359946. DOI: 10.1165/rcmb.2009-0415OC. View

16.

Jin Y, Tanaka A, Choi A, Ryter S . Autophagic proteins: new facets of the oxygen paradox. Autophagy. 2012; 8(3):426-8. PMC: 3337844. DOI: 10.4161/auto.19258. View

17.

Hayes M, Curley G, Ansari B, Laffey J . Clinical review: Stem cell therapies for acute lung injury/acute respiratory distress syndrome - hope or hype?. Crit Care. 2012; 16(2):205. PMC: 3681334. DOI: 10.1186/cc10570. View

18.

Taylor W, Hanson J, Turner G, White N, Dondorp A . Respiratory manifestations of malaria. Chest. 2012; 142(2):492-505. DOI: 10.1378/chest.11-2655. View

19.

Subramani S, Malhotra V . Non-autophagic roles of autophagy-related proteins. EMBO Rep. 2013; 14(2):143-51. PMC: 3566844. DOI: 10.1038/embor.2012.220. View

20.

Levitt J, Calfee C, Goldstein B, Vojnik R, Matthay M . Early acute lung injury: criteria for identifying lung injury prior to the need for positive pressure ventilation*. Crit Care Med. 2013; 41(8):1929-37. PMC: 3748809. DOI: 10.1097/CCM.0b013e31828a3d99. View