Sepsis is a systemic inflammatory response syndrome with high mortality. Acute liver injury is an independent predictor for poor prognosis in septic patients. Polygonatum sibiricum polysaccharides (PSP) have been reported to possess anti-inflammatory and hepatoprotective activities. To evaluate the effects of PSP on septic liver injury and demonstrate the potential molecular mechanisms, the septic acute liver injury (SALI) model was established in BALB/c mice via intraperitoneal injection of lipopolysaccharide (LPS). We found that PSP treatment could remarkably reduce the 48 h mortality rate of septic mice; alleviate liver histopathologic damage; lower the activity of neutrophil infiltration marker MPO in liver tissue; and decrease the levels of liver function indexes AST, ALT, ALP, and TBIL, inflammatory cytokines TNFα and IL-6, and pyroptosis-related inflammatory cytokines IL-18 and IL-1β in serum. TUNEL staining and detecting GSDMD-NT protein expression level in liver tissue revealed that PSP could restrain excessive pyroptosis. In addition, PSP treatment reversed the upregulations of mRNA expression levels of the NLRP3/GSDMD signals in the liver. Our results indicated the potential protective role of PSP against SALI by inhibiting pyroptosis via NLRP3/GSDMD signals.

Introduction: Meridianin C (MC) is a marine-derived indole alkaloid that has demonstrated kinase inhibitory and anti-tumor activities. Despite its diverse biological properties, no previous reports have systematically evaluated the in vivo quantitative analysis of MC and its metabolites.Methods: In this study, MC was synthesized following a previously reported procedure with slight modifications. A sensitive, accurate, and reliable ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS) method was developed to simultaneously detect MC and its five major metabolites (MC-1-N-O-GluA, MC-1-N-O-SO₃H, MC-2′-N-O-GluA, MC-2′-N-O-SO₃H, and MC-O-GluA-didehydration) in rat plasma. Rats received a single oral dose of MC (100 mg/kg), and pharmacokinetic analysis was subsequently performed.Results: Pharmacokinetic data revealed that MC was rapidly absorbed, with a C_max of 44.8 ± 7.0 μmol/L, an AUC_0–48h of 232.0 ± 85.9 μmol·h/L, a T_max of 0.75 ± 0.27 h, and a t_1/2 of 17.7 ± 14.1 h. Plasma concentrations of MC were significantly higher than those of its metabolites, suggesting that MC remains the predominant circulating form after oral administration. The identified metabolites mainly resulted from hydroxylation combined with glucuronide conjugation, hydroxylation combined with sulfation, and hydration combined with glucuronide conjugation.Discussion: These findings demonstrate that the primary metabolic pathway of MC involves hydroxylation (phase I) followed by conjugation (phase II). To our knowledge, this represents the first systematic investigation of the pharmacokinetic characteristics of MC and its metabolites in rats. The study not only advances understanding of MC disposition but also provides a valuable reference for future pharmacokinetic evaluations of other marine-derived indole alkaloids.