Dahuang Zhechong pill attenuates CCl4-induced rat liver fibrosis via the PI3K-Akt signaling pathway

被引:65
作者
Gong, Zhenghua [1 ]
Lin, Jiayu [2 ]
Zheng, Jie [3 ]
Wei, Liya [1 ]
Liu, Li [1 ]
Peng, Yanzhong [4 ]
Liang, Weicheng [5 ]
Hu, Guoxin [4 ]
机构
[1] Peking Univ, Dept Ultrasound, Shenzhen Hosp, Shenzhen, Peoples R China
[2] Sun Yat Sen Univ, Dept Gastroenterol, Affiliated Hosp 8, Shenzhen, Peoples R China
[3] Peking Univ, Dept Tradit Chinese Med, Shenzhen Hosp, Shenzhen, Peoples R China
[4] Peking Univ, Dept Infect Dis, Shenzhen Hosp, Shenzhen 518036, Peoples R China
[5] Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Peoples R China
基金
中国国家自然科学基金;
关键词
CCl4; Chinese herb; liver fibrosis; PI3K; TRADITIONAL CHINESE MEDICINE; HEPATIC STELLATE CELLS; MOLECULAR TARGETS; KINASE; ACTIVATION; CIRRHOSIS; THERAPY; FORMULA;
D O I
10.1002/jcb.29378
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
It is well characterized that activated hepatic stellate cells (HSCs) exert critical functions in accelerating the progression of liver fibrosis. Previous studies have indicated that Dahuang Zhechong pill (DHZCP), a traditional Chinese herbal medicine, is capable of inactivating HSCs and thus attenuate the formation of liver fibrosis in rats. However, pharmacological mechanisms of DHZCP in alleviating liver fibrosis remain unclear. This study aims to investigate the antifibrotic role of DHZCP through inhibiting the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) pathway. DHZCP was found to significantly suppresses extracellular matrix formation and immune cell infiltration, thus alleviating liver fibrosis symptoms in the in vivo model. Moreover, DHZCP reduced serum levels of transforming growth factor beta 1 and tumor necrosis factor-alpha in rats with liver fibrosis. DHZCP treatment remarkably downregulated protein levels of PI3K and phosphorylated Akt, as well as fibrosis markers. In vitro experiments further demonstrated that DHZCP markedly suppressed HSCs proliferation by downregulating PI3K/Akt, which exerted a synergistic effect with the PI3K inhibitor LY294002. To sum up, our results confirmed that DHZCP exerted an antifibrotic effect in the animal model through inactivating the PI3K/Akt pathway, thus protecting rats from liver injury.
引用
收藏
页码:1431 / 1440
页数:10
相关论文
共 33 条
[1]   Phosphatidylinositol 3-kinase function is required for transforming growth factor β-mediated epithelial to mesenchymal transition and cell migration [J].
Bakin, AV ;
Tomlinson, AK ;
Bhowmick, NA ;
Moses, HL ;
Arteaga, CL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (47) :36803-36810
[2]   Targeting PI3 kinase in cancer [J].
Bauer, Todd M. ;
Patel, Manish R. ;
Infante, Jeffrey R. .
PHARMACOLOGY & THERAPEUTICS, 2015, 146 :53-60
[3]   Effects of dahuangzhechong pills on cytokines and mitogen activated protein kinase activation in rats with hepatic fibrosis [J].
Cai, Hong Bing ;
Sun, Xue Gang ;
Liu, Zhi Feng ;
Liu, Ya Wei ;
Tang, Jing ;
Liu, Qiang ;
Ji, Bao Min ;
Song, Yu Hong ;
Zhou, Ying Chun ;
Yang, Ming Hui ;
Lv, Zhi Ping .
JOURNAL OF ETHNOPHARMACOLOGY, 2010, 132 (01) :157-164
[4]  
Cheng Mu-Hua, 2008, Zhongguo Zhong Yao Za Zhi, V33, P564
[5]   Anti-fibrotic effects of thalidomide on hepatic stellate cells and dimethylnitrosamine-intoxicated rats [J].
Chong, Lee-Won ;
Hsu, Yi-Chao ;
Chiu, Yung-Tsung ;
Yang, Kuo-Ching ;
Huang, Tsau .
JOURNAL OF BIOMEDICAL SCIENCE, 2006, 13 (03) :403-418
[6]   Curcumin in Liver Diseases: A Systematic Review of the Cellular Mechanisms of Oxidative Stress and Clinical Perspective [J].
Farzaei, Mohammad Hosein ;
Zobeiri, Mahdi ;
Parvizi, Fatemeh ;
El-Senduny, Fardous F. ;
Marmouzi, Ilias ;
Coy-Barrera, Ericsson ;
Naseri, Rozita ;
Nabavi, Seyed Mohammad ;
Rahimi, Roja ;
Abdollahi, Mohammad .
NUTRIENTS, 2018, 10 (07)
[7]   Genome-wide identification of long noncoding RNAs in CCl4-induced liver fibrosis via RNA sequencing [J].
Gong, Zhenghua ;
Tang, Jialin ;
Xiang, Tianxin ;
Lin, Jiaya ;
Deng, Chaowen ;
Peng, Yanzhong ;
Zheng, Jie ;
Hu, Guoxin .
MOLECULAR MEDICINE REPORTS, 2018, 18 (01) :299-307
[8]  
Gong ZH, 2018, J TRADIT CHIN MED, V38, P190
[9]   Management of liver cirrhosis between primary care and specialists [J].
Grattagliano, Ignazio ;
Ubaldi, Enzo ;
Bonfrate, Leonilde ;
Portincasa, Piero .
WORLD JOURNAL OF GASTROENTEROLOGY, 2011, 17 (18) :2273-2282
[10]   PI3K-PKB/Akt Pathway [J].
Hemmings, Brian A. ;
Restuccia, David F. .
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY, 2012, 4 (09)