[Effects of nuclear factor kappaB and transforming growth factor beta1 in the anti-liver fibrosis process using Ginkgo biloba extract].
OBJECTIVE
To evaluate the effects of Ginkgo biloba extract (EGB) on CCl(4)-induced liver fibrosis and to investigate the underlying mechanisms.


METHODS
Rats were divided into the following groups: normal control group, CCl(4) model group, low dose EGB group, moderate dose EGB group and high dose EGB group. The rat liver fibrosis model was induced by intraperitoneal injection of CCl(4) twice a week for 8 weeks. The model rats of the three EGB treated groups were given 0.25 g/kg, 0.5 g/kg, 1.0 g/kg of EGB by stomach tubes every day. At the end of the eighth week, the blood and liver specimens were obtained. The expressions of nuclear factor kappaB (NF-kappaB) P65, and alpha-smooth muscle actin (alpha-SMA) were detected by immunohistochemistry. Radioimmunoassay was exploited to evaluate serum hyaluronic acid (HA) and laminin (LN) levels. Electrophoretic mobility shift assay (EMSA) was used to confirm the nuclear translocation activity of NF-kappaB in liver tissues. The mRNA expression of transforming growth factor-beta1 (TGFbeta1) and collagen I was determined by RT-PCR. Malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in liver tissues and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the sera were also examined.


RESULTS
CCl(4) administration induced liver fibrosis, which was inhibited by EGB in a dose-dependent manner. The histopathologic scores of liver fibrosis, the levels of serum ALT, AST, HA and LN were significantly lower in the rats treated with EGB compared with those not treated (P <0.01 or P <0.05). SOD and GSH-Px activities were notably elevated and MDA content was significantly lower in the rats treated with EGB (P <0.01 or P <0.05), indicating reduced oxidative stress. Immunohistochemical staining demonstrated inhibition of hepatic stellate cell (HSC) activation (in terms of alpha-SMA expression) and NF-kappaB P65 expression in the livers of the EGB-treated rats. As determined by EMSA and RT-PCR, activation of NF-kappaB, the mRNA expression of TGFbeta1 and collagen I were significantly higher in model group rats, but obviously lower in EGB treated rats.


CONCLUSIONS
EGB is able to ameliorate liver injury and prevent rats from CCl(4)-induced liver fibrosis by suppressing oxidative stress. This process may be related to inhibiting the expression of TGFbeta1 and the induction of NF-kappaB on HSC activation.
Liu
Shi-quan
SQ
Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, China. poempower@163.com
Yu
Jie-ping
JP
He
Lei
L
Yu
Hong-gang
HG
Luo
He-sheng
HS
D000818:Animals; D002251:Carbon Tetrachloride; D002252:Carbon Tetrachloride Poisoning; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D020441:Ginkgo biloba; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D016328:NF-kappa B / Q000096:biosynthesis* / Q000235:genetics; D008517:Phytotherapy; D018515:Plant Leaves; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics
D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D016212:Transforming Growth Factor beta; D002251:Carbon Tetrachloride