Effect of ligustrazine on mice model of hepatic veno-occlusive disease induced by Gynura segetum.
OBJECTIVE
To investigate the therapeutic effect of ligustrazine on hepatic veno-occlusive disease (HVOD) induced by Gynura segetum and the possible mechanism of it.


METHODS
Female Kunming mice (115) were randomly divided into four groups, gavaged with 30 g/kg per day Gynura segetum (group A), 30 g/kg per day Gynura segetum + 100 mg/kg per day ligustrazine (group B), 30 g/kg per day Gynura segetum + 200 mg/kg per day ligustrazine (group C) or 30 mL/kg per day phosphate-buffered saline (PBS) (group D). Thirty days later, all of the mice were killed. Blood samples and livers were harvested. Histological changes were evaluated by light microscopy. Liver function was measured, and the expression of tissue factor (TF), early growth response factor-1 (Egr-1) and nuclear factor-KBp65 (NF-KBp65) were determined by reverse transcription-polymerase chain reaction and Western blot.


RESULTS
A total of 24 mice in group A developed HVOD. Compared with the controls, they had increased liver ratio, serum total bilirubin (TBIL), direct bilirubin (DBIL), transaminase and decreased albumin (ALB) (P < 0.05). Administration of ligustrazine improved the clinical signs and biochemistry parameters in a dose-dependent manner. Compared with group A, the expression of TF, Egr-1 and NF-KB p65 decreased in groups B and C (P < 0.05).


CONCLUSIONS
Ligustrazine has a therapeutic effect on HVOD, improving clinical manifestations and liver function. The possible mechanism may be that ligustrazine could reduce the expression of TF by downregulating the expression of transcription factors: Egr-1 and NF-KB p65.
Department of Digestive Disease, The Second Xiang-Ya Hospital of Central South University, Changsha, Hunan Province, China.
Zhe
Z
Chen
Ji-Rong
JR
Huo
Li
L
Yang
Hong-Yi
HY
Zhu
D000818:Animals; D019659:Asteraceae; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D011719:Pyrazines / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012709:Serum Albumin / Q000378:metabolism; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D000637:Transaminases / Q000097:blood; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D004365:Drugs, Chinese Herbal; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D011719:Pyrazines; C498144:Rela protein, mouse; D012709:Serum Albumin; D051996:Transcription Factor RelA; D013925:Thromboplastin; D000637:Transaminases; D001663:Bilirubin; C017953:tetramethylpyrazine