Methyl ferulic acid attenuates liver fibrosis and hepatic stellate cell activation through the TGF-β1/Smad and NOX4/ROS pathways

被引：104

作者：

Cheng, Qi ^{[1
]}

Li, Chen ^{[1
]}

Yang, Cheng-fang ^{[1
]}

Zhong, Yu-juan ^{[1
]}

Wu, Dan ^{[1
]}

Shi, Lin ^{[1
]}

Chen, Li ^{[1
]}

Li, Yong-wen ^{[1
]}

Li, Li ^{[1
]}

机构：

[1] Guilin Med Univ, Coll Pharm, 109 Second North Ring Rd, Guilin 541004, Guangxi, Peoples R China

来源：

CHEMICO-BIOLOGICAL INTERACTIONS | 2019年 / 299卷

基金：

中国国家自然科学基金;

关键词：

Methyl ferulic acid; Liver fibrosis; Hepatic stellate cell activation; TGF-beta 1/Smad pathway; NOX4/ROS pathway; DINUCLEOTIDE PHOSPHATE OXIDASE; OXIDATIVE STRESS; TGF-BETA/SMAD; EXTRACELLULAR-MATRIX; IN-VIVO; INJURY; MECHANISMS; BETA; MICE; EXTRACT;

D O I：

10.1016/j.cbi.2018.12.006

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：

Liver fibrosis is a pathological wound-healing response caused by chronic liver damage due to a virus, auto-immune disorder, or drugs. Hepatic stellate cells (HSCs) play an essential role in the pathogenesis of liver fibrosis. Methyl ferulic acid (MFA), a biologically active monomer, has a protective effect on liver injury. However, the effects and roles of MFA in liver fibrosis remain unknown. The purpose of the current study was to investigate the effect of MFA on hepatic fibrosis and the underlying mechanisms. Human hepatic stellate LX2 cells were exposed to 5 mu g/L TGF-beta 1 for 48 h to stimulate liver fibrosis in vitro. Using MIT, RT-PCR and Western blot analysis, we revealed that MFA significantly inhibited the proliferation of LX-2 cells as well as decreased the expressions of a-SMA and type I collagen in LX-2 cells. SD rats were fed with ethanol, and this combined with the intraperitoneal injection of CCl4 induced liver fibrosis in vivo. We found that the administration of MFA markedly decreased the levels of hyaluronic acid (HA), procollagen type III (PC-III), type IV collagen (CIV) and laminin (LN) in the serum, inhibited the expression of a-smooth muscle actin (alpha-SMA) as well as type I and type III collagen, and up-regulated the ratio of MMP-2/TIMP-1 in rats. The antifibrotic effects of MFA were also evaluated by H&E staining and Masson's trichrome staining. In addition, further studies suggested that this protection by MFA from liver fibrosis was possibly related to the inhibition of TGF-beta 1/Smad and NOX4/ ROS signalling. In conclusion, our results demonstrate that MFA attenuated liver fibrosis and hepatic stellate cell activation by inhibiting the TGF-beta 1/Smad and NOX4/ROS signalling pathways.

引用

页码：131 / 139

页数：9

共 55 条

[31] Liuweiwuling tablets attenuate BDL-induced hepatic fibrosis via modulation of TGF-β/Smad and NF-κB signaling pathways [J].

Liu, Huimin ;

Dong, Fang ;

Li, Guangquan ;

Niu, Ming ;

Zhang, Congen ;

Han, Yanzhong ;

He, Lanzhi ;

Yin, Ping ;

Wang, Bin ;

Sang, Xiuxiu ;

Li, Ruishen ;

Wang, Jiabo ;

Bai, Zhaofang ;

Xiao, Xiaohe .

JOURNAL OF ETHNOPHARMACOLOGY, 2018, 210 :232-241

[32] Scoparone attenuates hepatic stellate cell activation through inhibiting TGF-β/Smad signaling pathway [J].

Liu, Xing ;

Zhao, Xiuxia .

BIOMEDICINE & PHARMACOTHERAPY, 2017, 93 :57-61

[33] Flavonoid-rich Scabiosa comosa inflorescence extract attenuates CCl4-induced hepatic fibrosis by modulating TGF-β-induced Smad3 phosphorylation [J].

Ma, Yuehong ;

Yuan, Hongwei ;

Jin, Rong ;

Bao, Xiaomei ;

Wang, Haisheng ;

Su, Xiaoli ;

Mu, Meng Gen Si Li ;

Liang, Jie ;

Zhang, Jianyu ;

Wu, Xingwei .

BIOMEDICINE & PHARMACOTHERAPY, 2018, 106 :426-433

[34] Beneficial Effects of Sorafenib on Splanchnic, Intrahepatic, and Portocollateral Circulations in Portal Hypertensive and Cirrhotic Rats [J].

Mejias, Marc ;

Garcia-Pras, Ester ;

Tiani, Carolina ;

Miquel, Rosa ;

Bosch, Jaime ;

Fernandez, Mercedes .

HEPATOLOGY, 2009, 49 (04) :1245-1256

[35] Stimulation and proliferation of primary rat hepatic stellate cells by cytochrome P450 2E1-derived reactive oxygen species [J].

Nieto, N ;

Friedman, SL ;

Cederbaum, A .

HEPATOLOGY, 2002, 35 (01) :62-73

[36] Quantitative interaction analysis permits molecular insights into functional NOX4 NADPH oxidase heterodimer assembly [J].

O'Neill, Sharon ;

Mathis, Magalie ;

Kovacic, Lidija ;

Zhang, Suisheng ;

Reinhardt, Jurgen ;

Scholz, Dimitri ;

Schopfer, Ulrich ;

Bouhelal, Rochdi ;

Knaus, Ulla G. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2018, 293 (23) :8750-8760

[37] Inhibition of Apoptosis Protects Mice from Ethanol-Mediated Acceleration of Early Markers of CCl4-Induced Fibrosis but not Steatosis or Inflammation [J].

Roychowdhury, Sanjoy ;

Chiang, Dian J. ;

Mandal, Palash ;

McMullen, Megan R. ;

Liu, Xiuli ;

Cohen, Jessica I. ;

Pollard, John ;

Feldstein, Ariel E. ;

Nagy, Laura E. .

ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 2012, 36 (07) :1139-1147

[38] Role of Oxidative Stress and Molecular Changes in Liver Fibrosis: A Review [J].

Sanchez-Valle, V. ;

Chavez-Tapia, N. C. ;

Uribe, M. ;

Mendez-Sanchez, N. .

CURRENT MEDICINAL CHEMISTRY, 2012, 19 (28) :4850-4860

[39] Probucol attenuates ethanol-induced liver fibrosis in rats by inhibiting oxidative stress, extracellular matrix protein accumulation and cytokine production [J].

Su, Xuesong ;

Wang, Yanqiu ;

Zhou, Guangyu ;

Yang, Xu ;

Yu, Rui ;

Lin, Yan ;

Zheng, Changqing .

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 2014, 41 (01) :73-80

[40] Anthocyanins isolated from blueberry ameliorates CCl4 induced liver fibrosis by modulation of oxidative stress, inflammation and stellate cell activation in mice [J].

Sun, Jianchao ;

Wu, Yafeng ;

Long, Cuizhen ;

He, Ping ;

Gu, Junying ;

Yang, Lei ;

Liang, Yaodong ;

Wang, Yuping .

FOOD AND CHEMICAL TOXICOLOGY, 2018, 120 :491-499

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