Acanthoic acid, a diterpene in Acanthopanax koreanum, ameliorates the development of liver fibrosis via LXRs signals
Acanthoic acid, a diterpene in Acanthopanax koreanum, ameliorates the development of liver fibrosis via LXRs signals
复制标题
刺五加酸是朝鲜刺五加中的一种二萜，通过 LXR 信号改善肝纤维化的发展
DOI：
10.1016/j.cbi.2014.04.016
复制
发表时间：
2014-07-25
影响因子：
5.1
通讯作者：
Nan, Ji-xing
中科院分区：
文献类型：
--
作者：
Bai, Ting;Yao, You-li;Nan, Ji-xing
在四氯化碳(CCl4)诱导的小鼠和转化生长因子-β(TGF-β)刺激的肝星状细胞(HSCs)中，观察了肝X受体(LXRs)介导的棘酸(AA)改善肝纤维化的信号转导。AA是从五加科植物朝鲜五加的根中分离得到的。CCl4处理组小鼠用10%CCl4橄榄油(2mL/kg，连续8周)腹腔注射。AA治疗组小鼠灌胃AA(20 mg/kg或50 mg/kg)，每周3次，共8周。AA可降低CCl_4诱导的血清转氨酶和组织坏死因子-α水平，组织病理学染色进一步证实AA可逆转肝损伤。AA可减少肝纤维化标志物的表达，调节基质金属蛋白酶-13/TIMP-1的比值，从而进一步逆转肝纤维化的发展。加入转化生长因子-β(5 ng/ml)激活HSC-T6细胞2 h，再加入AA(1、3、10 mU/L)处理24 h后进行分析。收集细胞，提取蛋白，检测LXRs的表达。AA可抑制转化生长因子-β刺激的α-SMA表达，增加LXR-β的表达。在体内和体外实验中，AA可通过激活LXRα和LXRβ来调节CCl4诱导的肝纤维化，而仅通过激活LXRβ来抑制HSCs的激活。刺五加可能通过LXRs信号途径减轻CCl4诱导的肝纤维化。(C)2014爱思唯尔爱尔兰有限公司。保留所有权利。
Liver X receptors (LXRs)-mediated signals in acanthoic acid (AA) ameliorating liver fibrosis were examined in carbon tetrachloride (CCl4)-induced mice and TGF-beta stimulated hepatic stellate cells (HSCs). AA was isolated from the root of Acanthopanax koreanum Nakai (Araliaceae). CCl4-treated mice were intra-peritoneally injected with 10% CCl4 in olive oil (2 mL/kg for 8 weeks). In AA treated groups, mice were intragastrically administrated with AA (20 mg/kg or 50 mg/kg) 3 times per week for 8 weeks. Administration of AA reduced serum aminotransferase and tissue necrosis factor-a (TNF-alpha) levels evoked by CCl4, and the reverse of liver damage was further confirmed by histopathological staining. Administration of AA reduced the expression of fibrosis markers and regulated the ratio of MMP-13/TIMP-1, further reversed the development of liver fibrosis. TGF-beta (5 ng/ml) was added to activate HSC-T6 cells for 2 h, and then treated with AA (1, 3, or 10 mu mol/I) for 24 h before analysis. Cells were collected and proteins were extracted to detect the expressions of LXRs. AA could inhibit the expression of alpha-SMA stimulated by TGF-beta and increase the expression of LXR beta. In vivo and in vitro experiments, AA could modulate liver fibrosis induced by CCl4-treatment via activation of LXR alpha and LXR beta, while inhibit HSCs activation only via activation of LXR beta. Acanthoic acid might ameliorate liver fibrosis induced by CCl4 via LXRs signals. (C) 2014 Elsevier Ireland Ltd. All rights reserved.