Abstract: Objective: To investigate the effect of total alkaloids from the seed embryo of Nelumbo nucifera (TAENN) on inflammation in the livers of mice with acute liver failure (ALF) induced by lipopolysaccharide (LPS)/D-galactosamine (GalN). Methods: Kunming mice were randomly divided into four groups including normal control, ALF model, TAENN low-dosage (30 mg/kg) and TAENN high-dosage groups (100 mg/kg). The drug was administered by gavage once a day. After 2 weeks, the model group and two TAENN groups were intraperitoneally injected with LPS and GalN. The contents of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and prostaglandine E2 (PGE2) were determined by enzyme linked immunosorbent assay (ELISA). NO contents in livers were examined by Griess’ method. The transcription of TNF-α, IL-1β, IL-6, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in livers were analyzed by real-time PCR. The protein expression levels of iNOS and COX-2, and the phosphorylation levels of nuclear transcription factor -κB (NF-κB) p65 subunit at Ser536 in mouse livers were detected by immunoblotting. Results: TAENN declined the levels of TNF-α, IL-1β and IL-6 (P < 0.01) in the sera and livers of ALF model mice. In the livers of ALF model mice, the contents of inflammatory mediators such as NO and PGE2 were significantly decreased (P < 0.01) in response to TAENN. Moreover, TAENN does-dependently declined the transcription of the encoding genes such as TNF-α, IL-1β, IL-6, iNOS and COX-2 (P < 0.01) in livers. Consistently, the protein expression levels of iNOS and COX-2 were greatly reduced by TAENN (P < 0.01). Although the protein expression levels of p65 remained unchanged, the phosphorylation of p65 at Ser536 was remarkably inhibited after TAENN treatment (P < 0.01). Conclusion: TAENN inhibited inflammatory responses in the livers of mice with LPS/GalN-induced ALF. This anti-inflammation effect was associated with restrained NF-κB signaling and reduced expression of inflammatory cytokines and mediators.

Key words: total alkaloids from the seed embryo of Nelumbo nucifera, lipopolysaccharide/D-galactosamine, acute liver failure, inflammation