Total aralosides of aralia elata (Miq) seem (TASAES) ameliorate nonalcoholic steatohepatitis by modulating IRE1α-mediated JNK and NF-κB pathways in ApoE–/– mice

Ethnopharmacological relevanceTotal saponins of Aralia elata (Miq) Seem (TASAES) from the Chinese traditional herb Long ya Aralia chinensis L. is popularly used as a folk medicine to treat rheumatism, neurasthenia, diabetes, hepatitis and antivirus in Asian countries. However, there was poor study of TASAES on Non-alcoholic steatohepatitis (NASH), which is characterized by inflammatory responses and hepatocellular apoptosis exacerbating liver injury. This study aimed to clarify whether or not the anti-inflammatory and anti-apoptotic activities and protective mechanisms of the total aralosides of Aralia elata (Miq) Seem (TASAES) ameliorate NASH in a high-fat diet (HFD)-induced ApoE–/– mouse model.Material and methodsC57/BL6N and ApoE–/– mice were fed with HFD containing 0.3% cholesterol and 20% fat to induce NASH and then treated with TASAES (75,150 mg/kg/day, i.g.) for 12 weeks. Liver tissue was procured for histological examination, real-time RT-PCR and Western blot analysis.ResultsASAES treatment groups exhibited lower serum alanine and aspartate aminotransferases than the NASH group. TASAES could also reduce hepatic steatosis, as revealed by histological changes. In addition, TASAES treatment groups showed lower protein and mRNA expression levels of pro-inflammatory cytokines, such as IL-6, MCP-1, and TNF-α than NASH group. Reduced TUNEL-positive cells were also found in TASAES treatment groups. Western blot and immunohistochemical results indicated that TASAES regulated apoptosis and inflammation-related protein expression. Furthermore, TASAES treatment significantly reduced the phosphorylation of IRE1α, JNK and IκB and the downstream activation of NF-κB p65 was also reduced.ConclusionThese findings suggested that the ameliorative effects of TASASE in HFD-induced NASH were associated with the regulation of IRE1α-mediated JNK and NF-κB signal pathways, thereby protecting the liver against NASH.

Graphical abstractTotal aralosides of Aralia elata (Miq) Seem (TASAES) is the extracts of Aralia elata, which has many pharmacological activities.NF-κB and JNK are the two typical pathways mediating nonalcoholic steatohepatitis (NASH).In this study, we found that TASAES treatment could protect ApoE–/– mice from HFD-induced liver injury and NASH by suppressing inflammatory responses and hepatocyte apoptosis. Our observations demonstrated hat TASAES ameliorated NASH by activating IRE1α-mediated JNK and NF-κB pathways. Therefore, TASAES may be a potential drug that could protect cells against NASH. Potential clinical applications should be further investigated.Figure optionsDownload full-size imageDownload high-quality image (176 K)Download as PowerPoint slide