Protective Effect of Glycyrrhizin on Myocardial Ischemia/reperfusion Injury-induced Oxidative Stress, Inducible Nitric Oxide Synthase and Inflammatory Reactions Through High-mobility Group Box 1 and Mitogen-activated Protein Kinase Expression

Overview

Journal Exp Ther Med

Specialty Pathology

Date 2017 Aug 17

PMID 28810581

Citations 11

Authors

Xiangna Cai

Xin Wang

Jilin Li

Shuying Chen

Affiliations

Soon will be listed here.

Abstract

Glycyrrhizin, which is a type of perennial leguminous caudex, has been used in various Asian countries, including P.R. China, India and Japan, for thousands of years. The present study was designed to investigate the protective effect of glycyrrhizin on myocardial ischemia/reperfusion (I/R) injury through oxidative stress, inducible nitric oxide synthase (iNOS), and inflammatory reactions via high-mobility group box 1 (HMGB1) and mitogen-activated protein kinase (MAPK) expression. Sprague-Dawley rats were divided into five groups: Sham; myocardial I/R injury + non-treated; myocardial I/R injury + 2 mg/kg glycyrrhizin; myocardial I/R injury + 4 mg/kg glycyrrhizin; and myocardial I/R injury + 10 mg/kg glycyrrhizin. Pre-treatment with glycyrrhizin significantly reduced infarct size and inhibited creatine kinase, creatine kinase-MB, lactate dehydrogenase and cardiac troponin T activities in rats with myocardial I/R injury. Furthermore, glycyrrhizin treatment significantly suppressed oxidative stress, iNOS protein expression and inflammatory reactions in rats with myocardial I/R injury. Additionally, treatment with glycyrrhizin significantly decreased the release of HMGB1 from the cerebral cortex into the serum in rats with myocardial I/R injury. Notably, glycyrrhizin significantly suppressed p-ERK, p-p38 MAPK and p-c-Jun N-terminal kinase protein expressions, and promoted extracellular signal-regulated kinase protein expression in rats with myocardial I/R injury. Collectively, the present study indicates that the protective effect of glycyrrhizin may reduce myocardial I/R injury through oxidative stress, iNOS and inflammatory reactions, via HMGB1 and MAPK expression.

Citing Articles

Glycyrrhizin Ameliorates Cardiac Injury in Rats with Severe Acute Pancreatitis by Inhibiting Ferroptosis via the Keap1/Nrf2/HO-1 Pathway.

Cui Q, Wang W, Shi J, Lai F, Luo S, Du Y Dig Dis Sci. 2024; 69(7):2477-2487.

PMID: 38753240 DOI: 10.1007/s10620-024-08398-6.

Effect of Diammonium Glycyrrhizinate in Improving Focal Cerebral Ischemia-Reperfusion Injury in Rats Through Multiple Mechanisms.

Wang H, Zhang B, Dong W, Li Y, Zhao L, Zhang Y Dose Response. 2022; 20(4):15593258221142792.

PMID: 36479318 PMC: 9720820. DOI: 10.1177/15593258221142792.

Synthesis, Antiviral, and Antibacterial Activity of the Glycyrrhizic Acid and Glycyrrhetinic Acid Derivatives.

Mohammed E, Peng Y, Wang Z, Qiang X, Zhao Q Russ J Bioorg Chem. 2022; 48(5):906-918.

PMID: 35919388 PMC: 9333650. DOI: 10.1134/S1068162022050132.

Paracrine signal emanating from stressed cardiomyocytes aggravates inflammatory microenvironment in diabetic cardiomyopathy.

Kaur N, Ruiz-Velasco A, Raja R, Howell G, Miller J, Abouleisa R iScience. 2022; 25(3):103973.

PMID: 35281739 PMC: 8905320. DOI: 10.1016/j.isci.2022.103973.

Promising Therapeutic Candidate for Myocardial Ischemia/Reperfusion Injury: What Are the Possible Mechanisms and Roles of Phytochemicals?.

Chen C, Yu L, Cheng B, Xu J, Cai Y, Jin J Front Cardiovasc Med. 2022; 8:792592.

PMID: 35252368 PMC: 8893235. DOI: 10.3389/fcvm.2021.792592.

References

Ye Y, Perez-Polo J, Birnbaum Y . Protecting against ischemia-reperfusion injury: antiplatelet drugs, statins, and their potential interactions. Ann N Y Acad Sci. 2010; 1207:76-82. DOI: 10.1111/j.1749-6632.2010.05725.x. View

Chan W, Taylor A, Ellims A, Lefkovits L, Wong C, Kingwell B . Effect of iron chelation on myocardial infarct size and oxidative stress in ST-elevation-myocardial infarction. Circ Cardiovasc Interv. 2012; 5(2):270-8. DOI: 10.1161/CIRCINTERVENTIONS.111.966226. View

Geng Z, Huang L, Song M, Song Y . Protective effect of a polysaccharide from Salvia miltiorrhiza on isoproterenol (ISO)-induced myocardial injury in rats. Carbohydr Polym. 2015; 132:638-42. DOI: 10.1016/j.carbpol.2015.06.086. View

Jose R, Sajitha G, Augusti K . A review on the role of nutraceuticals as simple as se(2+) to complex organic molecules such as glycyrrhizin that prevent as well as cure diseases. Indian J Clin Biochem. 2014; 29(2):119-32. PMC: 3990793. DOI: 10.1007/s12291-013-0362-8. View

Qiu J, Nishimura M, Wang Y, Sims J, Qiu S, Savitz S . Early release of HMGB-1 from neurons after the onset of brain ischemia. J Cereb Blood Flow Metab. 2007; 28(5):927-38. DOI: 10.1038/sj.jcbfm.9600582. View

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

Wang Z, Hsieh C, Liu W, Yin M . Glycyrrhizic acid attenuated glycative stress in kidney of diabetic mice through enhancing glyoxalase pathway. Mol Nutr Food Res. 2014; 58(7):1426-35. DOI: 10.1002/mnfr.201300910. View

He S, Gao M, Fu Y, Zhang Y . Glycyrrhizic acid inhibits leukemia cell growth and migration via blocking AKT/mTOR/STAT3 signaling. Int J Clin Exp Pathol. 2015; 8(5):5175-81. PMC: 4503086. View

Zaitone S, Abo-Gresha N . Rosuvastatin promotes angiogenesis and reverses isoproterenol-induced acute myocardial infarction in rats: role of iNOS and VEGF. Eur J Pharmacol. 2012; 691(1-3):134-42. DOI: 10.1016/j.ejphar.2012.06.022. View

10.

Zhang J, Wu Y, Weng Z, Zhou T, Feng T, Lin Y . Glycyrrhizin protects brain against ischemia-reperfusion injury in mice through HMGB1-TLR4-IL-17A signaling pathway. Brain Res. 2014; 1582:176-86. DOI: 10.1016/j.brainres.2014.07.002. View

11.

Liehn E, Tuchscheerer N, Kanzler I, Drechsler M, Fraemohs L, Schuh A . Double-edged role of the CXCL12/CXCR4 axis in experimental myocardial infarction. J Am Coll Cardiol. 2011; 58(23):2415-23. DOI: 10.1016/j.jacc.2011.08.033. View

12.

Yung M, Chan D, Liu V, Yao K, Ngan H . Activation of AMPK inhibits cervical cancer cell growth through AKT/FOXO3a/FOXM1 signaling cascade. BMC Cancer. 2013; 13:327. PMC: 3702529. DOI: 10.1186/1471-2407-13-327. View

13.

Chen T, Liao F, Yang Y, Wang J . Inhibition of inducible nitric oxide synthase ameliorates myocardial ischemia/reperfusion injury - induced acute renal injury. Transplant Proc. 2014; 46(4):1123-6. DOI: 10.1016/j.transproceed.2013.12.018. View

14.

Frost R, Nystrom G, Burrows P, Lang C . Temporal differences in the ability of ethanol to modulate endotoxin-induced increases in inflammatory cytokines in muscle under in vivo conditions. Alcohol Clin Exp Res. 2005; 29(7):1247-56. DOI: 10.1097/01.alc.0000171935.06914.5d. View

15.

Jeong C, Yoo K, Lee S, Jeong H, Lee C, Kim S . Curcumin protects against regional myocardial ischemia/reperfusion injury through activation of RISK/GSK-3β and inhibition of p38 MAPK and JNK. J Cardiovasc Pharmacol Ther. 2012; 17(4):387-94. DOI: 10.1177/1074248412438102. View

16.

Yang X, Liu Y, Wang L, Cui L, Wang T, Ge Y . Reduction in myocardial infarct size by postconditioning in patients after percutaneous coronary intervention. J Invasive Cardiol. 2007; 19(10):424-30. View

17.

Wang Z, Wang Y, Ye J, Lu X, Cheng Y, Xiang L . bFGF attenuates endoplasmic reticulum stress and mitochondrial injury on myocardial ischaemia/reperfusion via activation of PI3K/Akt/ERK1/2 pathway. J Cell Mol Med. 2014; 19(3):595-607. PMC: 4369816. DOI: 10.1111/jcmm.12346. View

18.

Nogueira-Machado J, de Oliveira Volpe C . HMGB-1 as a target for inflammation controlling. Recent Pat Endocr Metab Immune Drug Discov. 2012; 6(3):201-9. DOI: 10.2174/187221412802481784. View

19.

Xiong J, Wang Q, Xue F, Yuan Y, Li S, Liu J . Comparison of cardioprotective and anti-inflammatory effects of ischemia pre- and postconditioning in rats with myocardial ischemia-reperfusion injury. Inflamm Res. 2011; 60(6):547-54. DOI: 10.1007/s00011-010-0303-4. View

20.

Kim Y, Kim H, Chang K . Glycyrrhizin reduces HMGB1 secretion in lipopolysaccharide-activated RAW 264.7 cells and endotoxemic mice by p38/Nrf2-dependent induction of HO-1. Int Immunopharmacol. 2015; 26(1):112-8. DOI: 10.1016/j.intimp.2015.03.014. View