Luo Yun, Dong Xi, Yu Yingli, Sun Guibo, Sun Xiaobo
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.
Academy of Chinese Materia Medica, Wenzhou Medical University, Wenzhou, Zhejiang, China.
J Ethnopharmacol. 2015 Apr 2;163:241-50. doi: 10.1016/j.jep.2015.01.017. Epub 2015 Feb 2.
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.
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.
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.
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.
龙牙楤木（Aralia elata (Miq) Seem）中的总皂苷（TASAES），龙牙楤木是一种中国传统草药，在亚洲国家被广泛用作民间药物来治疗风湿病、神经衰弱、糖尿病、肝炎和抗病毒。然而，关于TASAES对非酒精性脂肪性肝炎（NASH）的研究较少，NASH的特征是炎症反应和肝细胞凋亡加剧肝损伤。本研究旨在阐明龙牙楤木（Aralia elata (Miq) Seem）总皂苷（TASAES）的抗炎和抗凋亡活性及保护机制是否能改善高脂饮食（HFD）诱导的ApoE-/-小鼠模型中的NASH。
将C57/BL6N和ApoE-/-小鼠喂食含0.3%胆固醇和20%脂肪的HFD以诱导NASH，然后用TASAES（75、150mg/kg/天，腹腔注射）治疗12周。获取肝脏组织用于组织学检查、实时RT-PCR和蛋白质印迹分析。
ASAES治疗组的血清丙氨酸和天冬氨酸转氨酶低于NASH组。组织学变化显示，TASAES还可减轻肝脏脂肪变性。此外，TASAES治疗组的促炎细胞因子如IL-6、MCP-1和TNF-α的蛋白质和mRNA表达水平低于NASH组。在TASAES治疗组中也发现TUNEL阳性细胞减少。蛋白质印迹和免疫组织化学结果表明，TASAES调节凋亡和炎症相关蛋白表达。此外，TASAES治疗显著降低了IRE1α、JNK和IκB的磷酸化，NF-κB p65的下游激活也降低。
这些发现表明，TASASE对HFD诱导的NASH的改善作用与IRE1α介导的JNK和NF-κB信号通路的调节有关，从而保护肝脏免受NASH的侵害。
