Prevention of Free Fatty Acid-Induced Hepatic Lipotoxicity in HepG2 Cells by Magnesium Isoglycyrrhizinate in vitro

Abstract

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease that threatens public health, and current therapies remain limited. This study investigated the protective effect of magnesium isoglycyrrhizinate (MGL), a novel compound, against free fatty acid (FFA)-induced lipotoxicity in a cellular model of steatosis. Methods: HepG2 cells were incubated with 1 mmol/l FFAs together with MGL for 24 h. Cell viability was assessed using the MTT assay. Cell apoptosis was determined by Hoechst staining. Intracellular lipids were measured by flow cytometry using Nile red. Mitochondrial function was analyzed by detecting transmembrane potential, cytochrome c release and reactive oxygen species’ production. Results: MGL protected cell viability and dramatically decreased FFA-induced cell apoptosis and lipid accumulation. MGL was found to inhibit mitochondrial transmembrane polarization, and decrease mitochondrial cytochrome c release and the generation of reactive oxygen species. Conclusion: This study demonstrated that MGL attenuates FFA-induced lipotoxicity by reducing mitochondrial damage, which indicates a promising therapeutic intervention for NAFLD.

Magnesium isoglycyrrhizinate ameliorates doxorubicin‑induced acute cardiac and hepatic toxicity via anti‑oxidant and anti‑apoptotic mechanisms in mice

“…Previous studies have demonstrated that MgIG may inhibit inflammatory responses in through the phospholipase A 2 /arachidonic acid and signal transducer and activator of transcription 3 pathways thus protecting liver function (5,6). Furthermore, MgIG protects liver cells from hypoxia-reoxygenation, ischemia/reperfusion and free fatty acid-induced injury (7)(8)(9). It has been suggested that MgIG exhibits potential hepatoprotective activity against hepatotoxicity induced by anticancer drugs (10).…”

Anti-inflammatory Activity of Magnesium Isoglycyrrhizinate Through Inhibition of Phospholipase A2/Arachidonic Acid Pathway

“…There are two isomers of GA, i.e., 18α-GA and 18β-GA. Magnesium isoglycyrrhizinate (MgIG), a magnesium salt of 18α-GA stereoisomer, is currently used as an anti-inflammatory and hepatoprotective agent in the treatment of inflammatory liver diseases. It has been shown to suppress liver inflammatory response, protect against tissue injury, and improve liver function [16][17][18][19][20][21][22]. However, the molecular mechanism by which MgIG exerts its anti-inflammatory effects remains unknown.…”

Hepatic lipid composition differs between ob/ob and ob/+ control mice as determined by using in vivo localized proton magnetic resonance spectroscopy

“…This metabolic condition causes a redistribution of fat storage from fat pads to non-adipose tissue such as liver, skeletal muscle, heart and pancreas. This increased uptake and storage of lipids in non-adipose tissues is thought to induce cell damage and apoptosis [29,30]. For example in liver, which plays a unique role in controlling carbohydrate and lipid homeostasis, impairment of mitochondria has been reported [31].…”