[Effects of the mixture of Swertia pseudochinensis Hara and Silybum marianum Gaertn extracts on CCl(4)-induced liver injury in rats with non-alcoholic fatty liver disease].
OBJECTIVE
To study the mechanism of liver injury induced by carbon tetrachloride (CCl(4)) in rats with non-alcoholic fatty liver disease (NAFLD), and the therapeutic effects of the extract mixture of Dangyao (Swertia pseudochinensis Hara) and Shuifeiji (Silybum marianum Gaertn) on NAFLD rats with liver injury.


METHODS
Male Wistar rats were randomized into normal control group, CCl(4) group, high-fat diet group, high-fat diet plus CCl(4) injection group (model group), diammonium glycyrrhizinate group and extract mixture group. Except the normal control and CCl(4) groups, rats were fed with high-fat diet (88% normal chow, 10% lard and 2% cholesterol) to induce NAFLD. Diammonium glycyrrhizinate and extracts were given by gavage. After eight weeks, a nonlethal dose of CCl(4) was injected intraperitoneally to all rats except the normal and high-fat diet groups. And 48 h later, all rats were sacrificed, and serum and liver tissues were collected for further study. Paraffin-processed liver tissue was stained with hematoxylin-eosin (HE) to observe the pathological changes. Serum alamine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured. The levels of triacylglycerol (TAG), malondialdehyde (MDA) and glutathione (GSH) in liver tissues were also examined. Expression of uncoupling protein 2 (UCP2) was determined by reverse transcription-polymerase chain reaction and Western blotting.


RESULTS
Liver sections stained with HE showed that the histopathological changes in the normal control group and the CCl(4) group were mild; massive hepatosteatosis diffusing in lobules was shown in the high-fat diet groups; steatosis, hepatocellular ballooning degeneration and inflammatory infiltration were severe around the central vein in sections of the model group. Compared with the model group, hepatosteatosis and ballooning were significantly attenuated in the treatment groups. Levels of serum ALT and AST, contents of TAG and MDA and the UCP2 expression in liver tissues of the model group increased obviously, while the level of liver GSH decreased. Compared with rats in the model group, the above biomarkers in the treatment groups were improved significantly.


CONCLUSIONS
The mixture of Dangyao and Shuifeiji extracts can decrease the susceptibility and degree of liver injury induced by hepatotoxin in rats with NAFLD. Regulation of the balance of pro- and anti-oxidative stress factors is involved in the mechanism.
Institute of Digestive Disease, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
Zhi-min
ZM
Mao
Hai-yan
HY
Song
Li-li
LL
Yang
Tao
T
Liu
Dong-fei
DF
Li
Pei-yong
PY
Zheng
Ping
P
Liu
Guang
G
Ji
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D059305:Diet, High-Fat; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D005234:Fatty Liver / Q000150:complications*; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D020944:Silybum marianum; D065626:Non-alcoholic Fatty Liver Disease; D051381:Rats; D017208:Rats, Wistar; D029967:Swertia; D014280:Triglycerides / Q000378:metabolism
D004365:Drugs, Chinese Herbal; D014280:Triglycerides; D008315:Malondialdehyde; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione