Magnesium isoglycyrrhizinate shows hepatoprotective effects in a cyclophosphamide-induced model of hepatic injury.

Wenjiao Jiang,Jingyan Liu,Guangji Wang,Qianfeng Lu,Yilin Sun,Kun Hao,Peijin Li,Xue Pei

doi:10.18632/oncotarget.16629

Abstract

The purpose of the current study was to investigate the effect of Magnesium Isoglycyrrhizinate (GM) on cyclophosphamide (CP)-induced hepatic injury in vivo and in vitro. The results demonstrated that GM exerted a protective effect on CP-induced acute liver injury, as evidenced by the alleviations of hepatic pathological damage and serum transaminase activities. Meantime, GM attenuated serum and HepG2 cell supernatant levels of TNF-α, IL-6, IL-1β, SOD and MDA. Western blot results presented that GM down-regulated the expressions of the microtubule associated protein 1A/1B-light chain 3 (LC3), Lysosome associated membrane protein-1 (LAMP-1), p-phosphatidylinositol 3-kinase (PI3K), p-protein Kinase B(Akt), p-mechanistic target of rapamycin(mTOR), p-ribosomal protein S6 kinase 70 kDa (p70S6K), p-4E binding protein 1(4EBP1), p- inhibitor of NF-κB(IκB)α and p-nuclear factor kappa B(NF-κB)p65 in CP-stimulated hepatic tissue and HepG2 cells. Taken together, our results suggested that GM showed beneficial effect on CP-induced liver injury through NF-κB-mediated inflammation and PI3K/Akt/mTOR/p70S6K/4EBP1 axis-mediated autophagy in vivo and in vitro.

Highlights

Cyclophosphamide (CP) is one of the universally used antineoplastic drugs for its therapeutic effects against various types of tumors, multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus
The results demonstrated that GM exerted a protective effect on CP-induced acute liver injury, as evidenced by the alleviations of hepatic pathological damage and serum transaminase activities
Western blot results presented that GM down-regulated the expressions of the microtubule associated protein 1A/1B-light chain 3 (LC3), Lysosome associated membrane protein-1 (LAMP-1), p-phosphatidylinositol 3-kinase (PI3K), p-protein Kinase B(Akt), p-mechanistic target of rapamycin(mTOR), p-ribosomal protein S6 kinase 70 kDa (p70S6K), p-4E binding protein 1(4EBP1), pinhibitor of NF-κB(IκB)α and p-nuclear factor kappa B(NF-κB)p65 in CP-stimulated hepatic tissue and HepG2 cells

Summary

Introduction

Cyclophosphamide (CP) is one of the universally used antineoplastic drugs for its therapeutic effects against various types of tumors, multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. A special catabolic pathway, is a dynamic diverse process including the formation of autophagosomes, fusion of the autophagosome with the lysosome to turn into the autolysosome, as well as the degradation of cytoplasmic organelles or cytosolic components in the autolysosome [3]. During the response to some fluctuations beyond a certain threshold which was considered as ‘stress’, cells would take diverse action of stress response pathways to adapt their metabolism and protect themselves against potential damage to maintain survival. The core pathway of mammalian autophagy begins with the formation of a phagophore and involves several molecular components, such as Beclin 1 pathway and PI3K/Akt/mTOR pathway. The present study was aimed to investigate the effect of GM on the regulation of PI3K/ Akt/mTOR pathway

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