共 54 条
Sappanone A Alleviates the Severity of Carbon Tetrachloride-Induced Liver Fibrosis in Mice
被引:8
作者:
Qi, Jing
[1
]
Li, Lanqian
[2
,3
]
Yan, Xueqing
[1
]
Hua, Wenxi
[2
,3
,4
]
Zhou, Zixiong
[2
,3
,4
]
机构:
[1] Fujian Med Univ, Univ Town, Sch Basic Med Sci, Dept Biochem & Mol Biol, 1 Xuefu North Rd, Fuzhou 350122, Peoples R China
[2] Fujian Med Univ, Sch Basic Med Sci, Dept Pathol, Fuzhou 350122, Peoples R China
[3] Fujian Med Univ, Inst Oncol, Sch Basic Med Sci, Fuzhou 350122, Peoples R China
[4] Fujian Med Univ, Diagnost Pathol Ctr, Fuzhou 350122, Peoples R China
基金:
中国国家自然科学基金;
关键词:
liver fibrosis;
sappanone A;
oxidative stress;
inflammation;
M2;
polarization;
PPAR-GAMMA;
INFLAMMATION;
STEATOHEPATITIS;
ACTIVATION;
D O I:
10.3390/antiox12091718
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 major challenge to global health because of its various complications, including cirrhosis and hepatocarcinoma, while no effective treatment is available for it. Sappanone A (SA) is a homoisoflavonoid extracted from the heartwood of Caesalpinia sappan Linn. with anti-inflammatory and antioxidant properties. However, the effects of SA on hepatic fibrosis remain unknown. This study aimed to investigate the protective effects of SA on carbon tetrachloride (CCl4)-induced liver fibrosis in mice. To establish a liver fibrosis model, mice were treated intraperitoneally (i.p.) with CCl4 for 4 weeks. SA (25, 50, and 100 mg/kg body weight) was i.p. injected every other day during the same period. Our data indicated that SA decreased liver injury, fibrotic responses, and inflammation due to CCl4 exposure. Consistently, SA reduced oxidative stress and its-mediated hepatocyte death in fibrotic livers. Of note, SA could not directly affect the activation of hepatic stellate cells. Mechanistically, SA treatment lessened oxidative stress-triggered cell death in hepatocytes after CCl4 exposure. SA down-regulated the expression of M1 macrophage polarization markers (CD86 and iNOS) and up-regulated the expression of M2 macrophage polarization markers (CD163, IL-10, and Arg1) in livers and macrophages. Meanwhile, SA induced the activation of peroxisome proliferator-activated receptor gamma (PPAR & gamma;). However, decreased inflammatory responses and the trend of M2 macrophage polarization provided by SA were substantially abolished by SR202 (a PPAR & gamma; inhibitor) treatment in macrophages. Additionally, SA treatment promoted fibrosis regression. Taken together, our findings revealed that treatment with SA alleviated CCl4-induced fibrotic liver in mice through suppression of oxidative stress-mediated hepatocyte death and promotion of M2 macrophage polarization via PPAR & gamma;. Thus, SA might pave the way for a new hepatoprotective agent to treat liver fibrosis.
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页数:19
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