Work

Evaluation of the hepatoprotective effects and pharmacokinetics of pedunculoside in vitro and in vivo

Year: 2025

Type: article

Abstract: Pedunculoside (PE), a triterpenoid saponin isolated from Ilex rotunda Thunb., exhibits an anti-inflammatory effect; however, its hepatoprotective effects and pharmacokinetics are still unclear. Thus, an integrated strategy using network pharmacology and pharmacokinetics was used to investigate the hepatoprotective effects of PE. A simple, sensitive, and reliable LC-MS/MS method was established for the quantitative analysis of PE to elucidate its pharmacokinetics in normal rats and those with acute liver injury (ALI). LO 2 cells and carbon tetrachloride–treated rats were used to evaluate the hepatoprotective effects and mechanism of PE in vitro and in vivo , respectively. The blood concentration curve demonstrated a decrease in clearance (CL) and an increase in the area under the curve (AUC (0-∞) ) and mean residence time (MRT) in rats with ALI. Normal rats in the intravenous injection group had a CL of 36.80 L/h/kg, AUC (0-∞) of 1092.01 μg/L•h, and MRT (0-∞) of 0.93 h. In contrast, the CL of rats with ALI was 34.54 L/h/kg, AUC (0-∞) was 1170.01 μg/L•h, and MRT was 1.16 h. Similar results were obtained for rats in the intraperitoneal injection group. Qualitative studies of rat metabolites identified 19 metabolites, indicating that PE mainly undergoes phase I metabolism followed by phase II metabolism to a lesser extent. As rats with ALI showed a liver-targeting trend, network pharmacology was used to predict 20 potential ALI-related targets, among which the nuclear factor-kappa B (NF-κB) pathway had the strongest correlation. PE exhibited a protective effect on ALI by decreasing the levels of alanine transaminase, aspartate transaminase, and the pro-inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-1β, and IL-6, wherein the mechanism was related to the NF-κB pathway. Thus, PE exhibited a significant protective effect against ALI through the NF-κB pathway.

Source: European Journal of Pharmacology

DOI: 10.1016/j.ejphar.2025.178359