Gentiopicroside ameliorates CCl-induced liver injury in mice by regulating the PPAR-γ/Nrf2 and NF-κB/IκB signaling pathways

Abstract

Objective This study explored the mechanisms by which gentiopicroside protects against carbon tetrachloride (CCl 4 )-induced liver injury. Methods Male mice were randomly assigned to the control; CCl 4 ; bifendate 100 mg/kg; or gentiopicroside 25, 50, or 100 mg/kg groups. Both vehicle and drugs were administered intragastrically for 7 days. Mice were administered CCl 4 intraperitoneally 1 hour after the last drug dose. After 24 hours, we collected blood and liver samples for testing. Results Gentiopicroside significantly reduced serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase activities with corresponding reductions in hepatocyte denaturation and necrosis. Gentiopicroside enhanced superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and glutathione levels and reduced heme oxygenase 1 (HO-1) activity and malondialdehyde levels in the liver, and these effects were attributed to peroxisome proliferator-activated receptor (PPAR)-γ/nuclear factor erythroid 2-related factor 2 (Nrf2) activation. Meanwhile, gentiopicroside significantly downregulated HO-1 and upregulated SOD and GSH-Px at the mRNA level in the liver. Furthermore, gentiopicroside significantly suppressed serum tumor necrosis factor-α and interleukin-1β secretion, which was associated with the inhibition of nuclear factor-kappa B (NF-κB)/inhibitor of NF-κB (IκB). Conclusions Gentiopicroside ameliorated CCl 4 -induced liver injury in mice via the PPAR-γ/Nrf2 and NF-κB/IκB pathways.