Prevention of free fatty acid-induced hepatic lipotoxicity in HepG2 cells by magnesium isoglycyrrhizinate in vitro.
OBJECTIVE
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.


CONCLUSIONS
This study demonstrated that MGL attenuates FFA-induced lipotoxicity by reducing mitochondrial damage, which indicates a promising therapeutic intervention for NAFLD.
Cheng
Yuan
Y
Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, Jiangsu 210038, PR China.
Zhang
Juan
J
Shang
Jing
J
Zhang
Luyong
L
D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000187:drug effects / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000633:toxicity; D005234:Fatty Liver / Q000188:drug therapy* / Q000503:physiopathology; D005434:Flow Cytometry; D056945:Hep G2 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*
C521270:18alpha,20beta-hydroxy-11-oxo-norolean-12-en-3beta-yl-2-O-beta-D-glucopyranurosyl-alpha-D-glucopyranosiduronate magnesium tetrahydrate; D005230:Fatty Acids, Nonesterified; D020011:Protective Agents; D017382:Reactive Oxygen Species; D012503:Saponins; D014315:Triterpenes; D045304:Cytochromes c