Yun Luo1, Xi Dong2, Yingli Yu1, Guibo Sun3, Xiaobo Sun4. 1. Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, PR China. 2. Academy of Chinese Materia Medica, Wenzhou Medical University, Wenzhou, Zhejiang, China. 3. Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, PR China. Electronic address: sunguibo@126.com. 4. Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, PR China. Electronic address: sunsubmit@163.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Total 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 METHODS: C57/BL6N and ApoE-/- mice were fed with HFD containing 0.3% cholesterol and 20% fat to induce NASH and then treated with TASAES (75,150mg/kg/day, i.g.) for 12 weeks. Liver tissue was procured for histological examination, real-time RT-PCR and Western blot analysis. RESULTS: ASAES 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. CONCLUSION: These 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.
ETHNOPHARMACOLOGICAL RELEVANCE: Total 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 METHODS: C57/BL6N and ApoE-/- mice were fed with HFD containing 0.3% cholesterol and 20% fat to induce NASH and then treated with TASAES (75,150mg/kg/day, i.g.) for 12 weeks. Liver tissue was procured for histological examination, real-time RT-PCR and Western blot analysis. RESULTS:ASAES 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. CONCLUSION: These 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.