Protective role of magnesium isoglycyrrhizinate in non-alcoholic fatty liver disease and the associated molecular mechanisms

Abstract

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide and there is an urgent need to identify effective pharmacological strategies to treat NAFLD. For this purpose, in the present study, we examined the the possible molecular mechanisms responsible for the effects of MgIG and the protective effects of MgIG in a model of NAFLD. The human hepatic L02 cell line and oleic acid were employed to establish an in vitro model of NAFLD. The CCK-8 assay, Hoechst 33258 staining and Annexin V-PI staining were performed in order to evaluate cell viability and apoptosis. Oil red O staining was used to detect lipid accumulation within the L02 cells. We found that MgIG significantly inhibited lipid accumulation and protected the L02 cells against lipid accumulation-induced apoptosis. Key molecules involved in unfolded protein response (UPR) signaling were upregulated in lipid-overloaded hepatic cells whereas MgIG suppressed the activation of the UPR. Furthermore, MgIG significantly inhibited the expression of the downstream inflammatory cytokines which had been induced by lipid accumulation. Taken together, these findings suggest that the activation of UPR signaling induces the expression of inflammatory cytokines through the activation of nuclear factor-κB (NF-κB) in lipid-overloaded hepatic cells. In addition, MgIG may suppress the activation of UPR signaling thereby protecting hepatic cells from NAFLD‑induced injury.

Protective Effects of Magnesium Glycyrrhizinate on Methotrexate-Induced Hepatotoxicity and Intestinal Toxicity May Be by Reducing COX-2

“…At present, the protective effects of MgIG on liver injury are mainly attributed to STAT3 (Zhao Z. et al, 2017), hedgehog (Lu et al, 2017), NF-κB signaling pathway (Xu et al, 2016; Jiang et al, 2017a; Zhao X.J. et al, 2017) and phospholipase A2/arachidonic acid pathway (Xie et al, 2015).…”

Magnesium isoglycyrrhizinate has hepatoprotective effects in an oxaliplatin‑induced model of liver injury

“…The full name of MgiG is tetrahydrate magnesium 18α, 20β-hydroxy-11-oxon orolean-12-en-3β-yl-2-O-β-D-glucopyranurosyl-α-D-glucopy ranosiduronate ( 13 ). Previous studies have demonstrated that MgiG attenuates liver injury caused by toxins (carbon tetrachloride and D-galactosamine) and other factors, including free fatty acid, ethanol and ischemia/reperfusion ( 14 ). MgiG exerts a greater liver-protecting effect than glycyrrhizin or β-glycyrrhizic acid ( 15 - 17 ).…”

Magnesium Isoglycyrrhizinate Ameliorates Fibrosis and Disrupts TGF-β-Mediated SMAD Pathway in Activated Hepatic Stellate Cell Line LX2

“…However, we further argued that while these cells seemed to activate the apoptotic machinery, the cells did not exhibit higher cell death compared to activated LX2 cells when subjected to the same concentrations of MgIG. Therefore, this led us to hypothesize that (1) either LO2 cells were indeed more resistant to MgIG-induced cytotoxicity than LX2 cells or (2) that MgIG might indeed have cell specific hepatoprotective effects on LO2 cells, the latter being more plausible due to the number of mechanistic studies supporting its protective effects on hepatocytes ( Zheng et al, 2015 ; Xu et al, 2016 ; Lu et al, 2017 ; Wu et al, 2018 ). In the context of liver fibrosis, as the injury persist, apoptotic hepatocytes may trigger the activation of HSCs and thus deteriorate the fibrotic condition ( Puche et al, 2013 ).…”