Exploring the hepatoprotective effects of perillyl alcohol in the experimental models of acute liver injury

Aims: Acute liver injury (ALI), a severe and potentially fatal inflammation-mediated process of hepatocellular damage, remains a critical clinical concern. The goal of this study was to investigate the protective effects of Perillyl alcohol (POH), a naturally occurring monoterpene with potent anti-inflammatory properties, on LPS/D-GalN-induced ALI in both in vivo and in vitro models.

Materials and methods: In this study, POH was used as a pretreatment to assess its effects on ALI. In vivo and in vitro models of ALI were induced using lipopolysaccharide (LPS) plus D-Galactosamine (D-GalN). The therapeutic impact of POH was evaluated through measures of inflammation, oxidative stress, hepatocyte Apoptosis, and macrophage infiltration. Additionally, transcriptome and molecular docking analyses were performed to explore the molecular mechanisms underlying POH is protective effects.

Key findings: The experimental results revealed that POH pretreatment significantly alleviated ALI. POH dose-dependently reduced pro-inflammatory cytokine levels, macrophage infiltration, hepatocyte Apoptosis, and oxidative stress. Molecular analyses identified that POH inhibited the release of inflammatory factors by directly targeting NF-κB and NLRP3 proteins. The protective effects of POH were comparable to the effects of NF-κB and NLRP3 inhibitors (PDTC and MCC950, respectively).

Significance: This study demonstrates the potential of POH as a protective agent against LPS/D-GalN-induced ALI by modulating the NF-κB and NLRP3 signaling pathways. These findings provide valuable insights into the potential of natural anti-inflammatory compounds in liver injury management.

Acute liver injury; Inflammation; NF-κB; NLRP3; Perillyl alcohol.