Wen Jianxia, Wang Dan, Wang Jian, Wang Ruilin, Wei Shizhang, Zhao Yanling
Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China.
College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
Evid Based Complement Alternat Med. 2021 Mar 13;2021:5574010. doi: 10.1155/2021/5574010. eCollection 2021.
(AR), the dried root of (Fisch.) Bge. or (Fisch.) Bge. var. mongholicus (Bge) Hsiao, is a commonly used traditional Chinese medicine for the treatment of liver diseases. This study aimed to comprehensively evaluate the pharmacological action and explore the potential mechanism of AR on liver fibrosis. Rats were administered with carbon tetrachloride for eight weeks, followed by oral treatment with AR for six weeks. The efficacy was confirmed by measuring liver function and liver fibrosis levels. The underlying mechanisms were explored by detecting the expression of related proteins. AR significantly decreased the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), collagen IV (COL-IV), hyaluronic acid (HA), laminin (LN), and precollagen type III (PCIII). In addition, AR inhibited the deposition of collagen and the activation of hepatic stellate cells. Those data strongly demonstrated that AR alleviated liver fibrosis by CCl. In order to illustrate the potential inflammatory, the mRNA levels of IL-6, TNF-, and IL-1 were detected. Subsequently, immunohistochemistry analysis was performed to further verify the expression of type I collagen. Finally, the expression of key proteins in the inflammatory signaling pathway was detected. AR significantly reduced the expression of high-mobility group box 1 (HMGB1), TLR4, Myd88, RAGE, and NF- B p65 genes and proteins. In addition, western blotting showed AR decreased the protein expression of RAGE, p-MEK1/2, p-ERK1/2, and p-c-Jun. Taken together, our data reveal that AR significantly inhibits liver fibrosis by intervening in the HMGB1-mediated inflammatory signaling pathway and secretion signaling pathway. This study will provide valuable references for the in-depth research and development of against liver fibrosis.
（某药名，未给出具体中文），为（植物学名，未给出具体中文名）或（植物学名变种，未给出具体中文名）的干燥根，是治疗肝病常用的传统中药。本研究旨在全面评估（某药名）对肝纤维化的药理作用并探索其潜在机制。大鼠用四氯化碳处理八周，随后口服（某药名）六周。通过检测肝功能和肝纤维化水平来确认疗效。通过检测相关蛋白的表达来探索潜在机制。（某药名）显著降低了血清谷丙转氨酶（ALT）、谷草转氨酶（AST）、IV型胶原（COL-IV）、透明质酸（HA）、层粘连蛋白（LN）和III型前胶原（PCIII）的水平。此外，（某药名）抑制了胶原蛋白的沉积和肝星状细胞的活化。这些数据有力地证明（某药名）通过四氯化碳减轻了肝纤维化。为了阐明潜在炎症，检测了白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和白细胞介素-1（IL-1）的mRNA水平。随后，进行免疫组织化学分析以进一步验证I型胶原的表达。最后，检测炎症信号通路中关键蛋白的表达。（某药名）显著降低了高迁移率族蛋白B1（HMGB1）、Toll样受体4（TLR4）、髓样分化因子88（Myd88）、晚期糖基化终末产物受体（RAGE）和核因子κB p65（NF-κB p65）基因及蛋白的表达。此外，蛋白质印迹法显示（某药名）降低了RAGE、磷酸化丝裂原活化蛋白激酶1/2（p-MEK1/2）、磷酸化细胞外信号调节激酶1/2（p-ERK1/2）和磷酸化c-Jun的蛋白表达。综上所述，我们的数据表明（某药名）通过干预HMGB1介导的炎症信号通路和分泌信号通路显著抑制肝纤维化。本研究将为（某药名）抗肝纤维化的深入研究和开发提供有价值的参考。
