Gentiopicroside ameliorates CCl₄-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 (CCl4)-induced liver injury. Methods Male mice were randomly assigned to the control; CCl4; 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 CCl4 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 CCl4-induced liver injury in mice via the PPAR-γ/Nrf2 and NF-κB/IκB pathways.

Gentiopicroside improves non-alcoholic steatohepatitis by activating PPARα and suppressing HIF1

“…It is not unique that GPS is effective on NASH, accumulating evidence demonstrated that GPS could not only improve NAFLD but also encompass a wide range of effects in other metabolic diseases ( Liu et al, 2014 ). GPS significantly attenuated glucose tolerance, insulin resistance, and dyslipidemia, reduced the inflammatory response in liver injury, diabetes mellitus, and diabetic retinopathy ( Liu et al, 2017 ; Xiao et al, 2022 ; Zou et al, 2022 ; Wang et al, 2023 ; Zhang et al, 2023 ). However, the mechanisms underlying the hepatoprotective effects of GPS are not well understood, hence, we used untargeted and targeted metabolomics to investigate whether the benefits of GPS are associated with the modulation of internal metabolism.…”