Bai Ting, Yao You-li, Jin Xue-jun, Lian Li-hua, Li Qian, Yang Ning, Jin Quan, Wu Yan-ling, Nan Ji-xing
Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, China.
Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, China.
Chem Biol Interact. 2014 Jul 25;218:63-70. doi: 10.1016/j.cbi.2014.04.016. Epub 2014 May 5.
Liver X receptors (LXRs)-mediated signals in acanthoic acid (AA) ameliorating liver fibrosis were examined in carbon tetrachloride (CCl4)-induced mice and TGF-β stimulated hepatic stellate cells (HSCs). AA was isolated from the root of Acanthopanax koreanum Nakai (Araliaceae). CCl4-treated mice were intraperitoneally 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-α (TNF-α) 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-β (5 ng/ml) was added to activate HSC-T6 cells for 2 h, and then treated with AA (1, 3, or 10 μmol/l) for 24 h before analysis. Cells were collected and proteins were extracted to detect the expressions of LXRs. AA could inhibit the expression of α-SMA stimulated by TGF-β and increase the expression of LXRβ. In vivo and in vitro experiments, AA could modulate liver fibrosis induced by CCl4-treatment via activation of LXRα and LXRβ, while inhibit HSCs activation only via activation of LXRβ. Acanthoic acid might ameliorate liver fibrosis induced by CCl4 via LXRs signals.
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，研究了肝X受体（LXRs）介导的刺五加酸（AA）改善肝纤维化的信号通路。AA从五加科植物刺五加（Acanthopanax koreanum Nakai）的根中分离得到。CCl4处理的小鼠腹腔注射10% CCl4的橄榄油溶液（2 mL/kg，共8周）。在AA处理组中，小鼠每周3次灌胃给予AA（20 mg/kg或50 mg/kg），共8周。给予AA可降低CCl4引起的血清转氨酶和组织坏死因子-α（TNF-α）水平，组织病理学染色进一步证实了肝损伤的逆转。给予AA可降低纤维化标志物的表达并调节MMP-13/TIMP-1的比值，进一步逆转肝纤维化的发展。加入TGF-β（5 ng/ml）激活HSC-T6细胞2小时，然后在分析前用AA（1、3或10 μmol/l）处理24小时。收集细胞并提取蛋白质以检测LXRs的表达。AA可抑制TGF-β刺激的α-SMA表达并增加LXRβ的表达。在体内和体外实验中，AA可通过激活LXRα和LXRβ调节CCl4诱导的肝纤维化，而仅通过激活LXRβ抑制HSCs的激活。刺五加酸可能通过LXRs信号通路改善CCl4诱导的肝纤维化。
