Sophocarpine attenuates septic liver injury through suppression of the NLRP3 inflammasome via autophagy-mediated degradation.

Septic liver injury remains a challenge in sepsis treatment. Nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 3 (NLRP3) inflammasome activation has been suggested to be a major cause of hepatocyte cell death in liver diseases. However, insufficient research has been performed to explore the underlying mechanisms associated with this. In the present study, sophocarpine, a pharmaceutical monomer originally isolated from Sophora flavescens, was suggested to attenuate septic liver injury in a mouse cecal ligation and puncture (CLP) model. By utilizing western blotting, ELISA, H&E staining and immunohistochemistry, the results demonstrated that sophocarpine treatment reversed CLP-induced elevations in serum aspartate transaminase, alanine transaminase, interleukin (IL)-6 and IL-1ß levels. Additionally, sophocarpine appeared to have suppressed the activation of the NLRP3 inflammasome, as indicated by observed reductions in liver IL-1ß, NLRP3, caspase 1-p20 and gasdermin D-p30 protein levels. Further investigation suggested that sophocarpine-induced autophagy was essential for this suppression of NLRP3 inflammasome activation, the inhibition of which reversed the protective effects of sophocarpine on CLP-induced liver injury. Collectively, results from the present study suggested a protective role for sophocarpine against septic liver injury, where sophocarpine may suppress NLRP3 inflammasome activation by autophagy-mediated degradation.

Acetic acid alleviates the inflammatory response and liver injury in septic mice by increasing the expression of TRIM40.

Sepsis remains a significant health care issue in clinical practice due to its high mortality rate and healthcare cost, despite extensive efforts to better understand the pathophysiology of sepsis. The systemic inflammatory response often leads to severe liver injury, even acute liver dysfunction and failure. Acetic acid, as a type of chemical compound, has been reported to be an emerging drug for improving metabolic syndrome and inhibiting inflammation in rats and human. To verify the effects of acetic acid in protecting the liver and reducing the inflammatory response, a septic mouse model was established by cecal ligation and puncture (CLP), and then the CLP-model mice were treated with acetic acid or PBS. Following the treatment, it was determined that, in CLP-model mice, acetic acid could alleviate the inflammatory response by decreasing the expression of cytokines including interleukin-6 and tumor necrosis factor-α. Additionally, acetic acid also alleviated the liver injury, and the levels of alanine aminotransaminase, aspartate aminotransferase, Toll-like receptor (TLR)4 and nuclear factor-κB (NF-κB) were decreased. The expression of tripartite motif-containing protein (TRIM)40 was also upregulated significantly. Therefore, the authors of the current study hypothesized that acetic acid could decrease the inflammatory response by increasing the expression of TRIM40 and TRIM40 may regulate the activity of the TLR4 signaling pathway. To further illustrate the interaction between TRIM40 and the TLR4 signaling pathway, the authors collected macrophages from the peritoneal cavity by intraperitoneally administering mice with 5 ml ice-cold normal saline. Following the collection, peritoneal macrophages were treated with acetic acid, TRIM40 small interfering RNA or PBS. It was demonstrated that acetic acid upregulated the expression of TRIM40. When TRIM40 was silenced, the protective effect of acetic acid would be reversed as well. The results suggested that TRIM40 could act on and downregulate the activity of the TLR4 signaling pathway. TRIM40 is possibly the major target for acetic acid, which may function as a protective factor in septic mice.