Blockade of hedgehog pathway is required for the protective effects of magnesium isoglycyrrhizinate against ethanol‐induced hepatocyte steatosis and apoptosis

Abstract

Alcoholic liver disease (ALD), characterized by excessive deposition of lipids in hepatocytes, causes heavy health burden personally and socially. Mechanistically, hedgehog signaling was activated during the development of ALD, and exerted compelling role in regulating lipometabolism. The current promising intervention strategy is inhibition of lipid accumulation and apoptosis in hepatocytes. Magnesium isoglycyrrhizinate (MgIG) has been widely used in various liver diseases for its good hepatoprotective activities. However, the role of MgIG in ALD has not been elucidated. Therefore, this study was aimed to explore the role of MgIG and further identify the potential mechanisms. We found for the first time that MgIG reduced lipid accumulation, including triglyceride, and total cholesterol, probably via inducing peroxisome proliferator-activated receptor-alpha and inhibiting sterol regulatory element-binding protein-1c. Further, MgIG alleviated ethanol-induced oxidative stress, evidenced by reduced abundance of reactive oxygen species and increased levels of glutathione, superoxide dismutase, and mitochondrial transmembrane potential. Besides, MgIG protected hepatocytes from ethanol-induced apoptosis. In addition, MgIG dose-dependently suppressed hedgehog signaling. Of note was that disruption of hedgehog signaling could mimic the effects of MgIG, whereas activation of hedgehog signaling abrogated the effects of MgIG. These findings suggested that MgIG prevented ethanol-induced hepatocyte steatosis and apoptosis via a hedgehog signaling inhibition-dependent mechanism. © 2017 IUBMB Life, 69(7):540-552, 2017.

Magnesium isoglycyrrhizinate promotes the activated hepatic stellate cells apoptosis via endoplasmic reticulum stress and ameliorates fibrogenesis in vitro and in vivo

“…As a protective agent for liver cells, Magnesium Isoglycyrrhizinate (MgIG) has an effect of protecting liver cell membrane. We previously reported that MgIG protected the ethanol‐induced hepatocyte injury and further clarified the potential molecular mechanisms . Interestingly, whether MgIG improves the inflammatory microenvironment of liver fibrosis and activates the HSCs apoptosis has never been investigated.…”

Dihydroartemisinin attenuates alcoholic fatty liver through regulation of lipin‐1 signaling

“…We speculated that DHA as a natural product could regulate the serum TC through some other mechanisms, which is worthy of further investigations. In recent years, the important transcriptional regulators including PPARα and SREBP‐1c, and their downstream targets, such as FAS and CPT1, involved in β‐oxidation and fatty acid synthesis, have been identified as specific targets of ethanol action in the liver . We provide evidence suggesting that lipin‐1, a vital regulator, may be responsible for ethanol‐mediated impairment of a hepatic signaling network, influenced by DHA through regulation of its nucleocytoplasmic shuttling.…”

“…Liver histology was examined using hematoxylin‐eosin (H&E) staining as we previously described . Immunohistochemistry of liver section was performed by using antibodies against CD45, F4/80, and Cleaved‐caspase3 according to the previous study .…”

Magnesium isoglycyrrhizinate positively affects concanavalin A-induced liver damage by regulating macrophage polarization

“…Appearing in an early materia medica manuscript, "Shennong's Classic Materia Medica," it has since been applied across China in many contexts as a result of its characteristics (Yang et al, 2016). MgIG, a magnesium salt of the 18-alpha-glycyrrhizic acid stereoisomer and classified as a new molecular compound identified in the roots of the Glycyrrhiza glabra (licorice) tree (Lu, Xu, et al, 2017), is associated with anti-inflammatory and antioxidant properties and hepatic protection and liver function enhancement (He et al, 2010;Sun et al, 2007). For the inhibition of ethanol-induced lipid peroxidation, MgIG has also been used as a pharmaceutical for liver protection (Xie et al, 2015).…”