Protective effects of β-eudesmol against septic liver injury via inhibition of NF-κB signaling

Abstract

Purpose: To investigate the role of β-eudesmol in septic liver injury in mice.Methods: Mice were intraperitoneally injected with 50 or 100 mg/kg β-eudesmol, and then subjected to cecal ligation and puncture for the establishment of a septic model 2 h later. Haematoxylin and eosin staining was used to evaluate histopathological changes in the liver tissues. Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) staining and enzyme-linked immunosorbent assay (ELISA) were employed to determine liver damage, while inflammation and oxidative stress were evaluated by ELISA.Results: Liver tissues of septic mice showed infiltration of inflammatory cells, vacuolar degeneration and obscure nucleus. However, treatment with β-eudesmol ameliorated the histopathological changes (p < 0.01). Moreover, β-eudesmol also reduced hepatocyte apoptosis, and decreased the levels of biomarkers for liver damage. The up-regulation of TNF-α, IL-1β, IL-6 in septic mice were significantly down-regulated by β-eudesmol (p < 0.01), but increased the levels of superoxide dismutase (SOD) and glutathione (GSH) and decreased malondialdehyde (MDA) and myeloperoxidase (MPO) in order to protect the mice against sepsis. In addition, β-eudesmol attenuated the cecal ligation and punctureinduced up-regulation of p-p65 in mice (p < 0.01).Conclusion: β-Eudesmol exerts anti-inflammatory and anti-oxidant effects in septic mice by inactivating NF-κB signaling, and thus may be useful as a potential agent in the management of sepsis.

Saikosaponin A alleviates rat liver fibrosis by inhibiting Hedgehog signaling pathway-mediated autophagy and NLRP3 inflammasome

“…Consistently, SSa inhibits NLRP3 inflammasome and autophagy via AMPK/mTOR pathway, which induces the inactivation of pancreatic stellate cells, thereby improving pancreatic fibrosis [16]. Saikosaponin D can also suppress NLRP3 inflammasome activation to relieve liver fibrosis [10,18]. The present study showed that SSa diminished the CCl4-induced relative levels of markers of the NLRP3 inflammasome in liver tissues, indicating that SSa suppressed CCl4-induced activation of the NLRP3 inflammasome.…”

“…In addition, SSa and/or curcumin attenuate hepatic inflammation and fibrosis in carbon tetrachloride (CCl4)-treated rats [8]. Furthermore, saikosaponin D (SSd) alleviates liver fibrosis by regulating autophagy and the NLRP3 inflammasome [9,10]. However, the effect and mechanism of SSa on liver fibrosis remain unknown.…”

Procyanidin A1 improves sepsis-induced liver injury by inhibiting inflammation

“…Therefore, retardation of the activation of NF-κB suppresses the generation of inflammatory cytokines and liver injury [19]. The NF-κB pathway has been revealed as playing a role in the progression of sepsis [8][9][10]; however, whether PCA1 modulates NF-κB pathway thereby ameliorating sepsis remains unknown. In this study, the protein levels of p-p65/p65 and p-IκBα increased, and that of IκBα decreased after LPS treatment, but these changes were reversed by PCA1 treatment, indicating that PCA1 inhibited NF-κB pathway.…”

“…The NF-κB pathway has been shown to participate in the progression of sepsis [8][9][10]. However, whether PCA1 modulates the NF-κB pathway to attenuate sepsis progression remains unclear.…”