Abstract: AIM: To investigate the prophylactic and therapeutic effects and mechanisms of kwoninone in rats with experimental liver fibrosis.METHODS: The animal models with liver fibrosis were prepared in rats by administration of carbon tetrachloride (CCl₄ ). 28 SD rats were randomly divided into 4 groups: normal control group, model control group, kwoninone prophylactic group and kwoninone therapeutic group. After 10 weeks of administration, the levels of ALT, AST, TBA and GGT were measured in rat serum. The histopathological changes were observed by light microscopy and electromicroscopy. The expressions of matrix metalloproteinase-2 (MMP-2) mRNA in liver were detected by reverse transcription polymerase chain reaction. The expressions of proteins of MMP-2 in liver were determined by gelatin zymography.RESULTS: The serum levels of ALT, AST, TBA and GGT in liver fibrosis rats were decreased in the kwoninone prophylactic groups and therapeutic groups(P<0. 05, or P<0. 01). The levels of fibrogenesis in liver tissues were more significantly decreased in the kwoninone prophylactic groups and therapeutic groups than that in the model control groups. The formations of liver pseudoluboli were alleviated in the kwoninone prophylactic groups and therapeutic groups. Structures of liver cells were recovered and few collagenous fibers were found in Disse space in the kwoninone prophylactic groups and therapeutic groups. The levels of the liver fibrosis in kwoninone prophylactic group were lighter than that in the therapeutic groups.The levels of MMP-2 mRNA and proteins of MMP-2 in the liver significantly decreased in the kwoninone prophylactic groups and therapeutic groups.CONCLUSION: Kwoninone can protect and therapy liver fibrosis induced by CCl₄ in rats, down-regulate the expression of MMP-2mRNA and proteins of MMP-2 levels, accelerate the degradation of ECM, and inhibit the deposition of the ECM in liver.

Key words: kwoninone, carbon tetrachloride, liver fibrosis, reverse transcription polymerase chain reaction, matrix metalloproteinase-2, extracellular matrix, rats