Hesperidin Prevents Liver Fibrosis in Rats by Decreasing the Expression of Nuclear Factor-κB, Transforming Growth Factor-� and Connective Tissue Growth Factor

Pharmacology ◽  
2014 ◽  
Vol 94 (1-2) ◽  
pp. 80-89 ◽  
Author(s):  
J. Eliuth Pérez-Vargas ◽  
Natanael Zarco ◽  
Mineko Shibayama ◽  
José Segovia ◽  
Víctor Tsutsumi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Liver Fibrosis ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Transforming Growth Factor ◽  
Nuclear Factor Κb ◽  
Tissue Growth ◽  
Nuclear Factor

l-Theanine prevents carbon tetrachloride-induced liver fibrosis via inhibition of nuclear factor κB and down-regulation of transforming growth factor β and connective tissue growth factor

2015 ◽  
Vol 35 (2) ◽  
pp. 135-146 ◽  
Author(s):  
JE Pérez-Vargas ◽  
N Zarco ◽  
P Vergara ◽  
M Shibayama ◽  
J Segovia ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Growth Factor ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Hepatic Cirrhosis ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Nuclear Factor Κb ◽  
Tissue Growth ◽  
Nuclear Factor

Here we evaluated the ability of l-theanine in preventing experimental hepatic cirrhosis and investigated the roles of nuclear factor-κB (NF-κB) activation as well as transforming growth factor β (TGF-β) and connective tissue growth factor (CTGF) regulation. Experimental hepatic cirrhosis was established by the administration of carbon tetrachloride (CCl4) to rats (0.4 g/kg, intraperitoneally, three times per week, for 8 weeks), and at the same time, adding l-theanine (8.0 mg/kg) to the drinking water. Rats had ad libitum access to water and food throughout the treatment period. CCl4 treatment promoted NF-κB activation and increased the expression of both TGF-β and CTGF. CCl4 increased the serum activities of alanine aminotransferase and γ-glutamyl transpeptidase and the degree of lipid peroxidation, and it also induced a decrease in the glutathione and glutathione disulfide ratio. l-Theanine prevented increased expression of NF-κB and down-regulated the pro-inflammatory (interleukin (IL)-1β and IL-6) and profibrotic (TGF-β and CTGF) cytokines. Furthermore, the levels of messenger RNA encoding these proteins decreased in agreement with the expression levels. l-Theanine promoted the expression of the anti-inflammatory cytokine IL-10 and the fibrolytic enzyme metalloproteinase-13. Liver hydroxyproline contents and histopathological analysis demonstrated the anti-fibrotic effect of l-theanine. In conclusion, l-theanine prevents CCl4-induced experimental hepatic cirrhosis in rats by blocking the main pro-inflammatory and pro-fibrogenic signals.

scholarly journals Src Inhibition Attenuates Liver Fibrosis by Preventing Hepatic Stellate Cell Activation and Decreasing Connective Tissue Growth Factor

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 558 ◽  
Author(s):  
Hye-Young Seo ◽  
So-Hee Lee ◽  
Ji-Ha Lee ◽  
Yu Na Kang ◽  
Jae Seok Hwang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Liver Fibrosis ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Mouse Liver ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Tissue Growth ◽  
Type I ◽  
Induced Expression

The SRC kinase family comprises non-receptor tyrosine kinases that are ubiquitously expressed in all cell types. Although Src is reportedly activated in pulmonary and renal fibrosis, little is known regarding its role in liver fibrosis. This study investigated whether the inhibition of Src protects against liver fibrosis. The expression of Src was upregulated in thioacetamide (TAA)-induced fibrotic mouse liver and cirrhosis of patients, and phospho-Src was upregulated during activation of hepatic stellate cells (HSC). In addition, Src inhibition reduced the expression of α-smooth muscle actin (αSMA) in primary HSCs and suppressed transforming growth factor β (TGF-β)-induced expression of connective tissue growth factor (CTGF) in hepatocytes. Src inhibitor Saracatinib also attenuated TAA-induced expression of type I collagen, αSMA, and CTGF in mouse liver tissues. The antifibrotic effect of Src inhibitors was associated with the downregulation of Smad3, but not of signal transducer and activator of transcription 3 (STAT3). In addition, Src inhibition increased autophagy flux and protected against liver fibrosis. These results suggest that Src plays an important role in liver fibrosis and that Src inhibitors could be treat liver fibrosis.

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