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Protective effect and mechanism of flavonoids of Ardisa japonica on liver fibrosis in rats |
CAO Qing-sheng1 LI Zhi-chao2▲ HAN Li-wang1 |
1.Department of Pathology, Yutian Hospital of Tangshan City in Hebei Province, Yutian 064100, China;
2.Department of Pain, Yutian Traditional Chinese Medicine Hospital of Tangshan City in Hebei Province, Yutian 064100,China |
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Abstract Objective To study the protective effect and mechanism of flavonoids of Ardisa japonica (FAJ) on liver fibrosis.Methods Sixty rats were randomly divided into a normal control group, a model group, a high-dose of FAJ group (600 mg/kg), a medium-dose of FAJ group (400 mg/kg), and a low-dose of FAJ group (200 mg/kg), with 12 rats in each group.Hepatic fibrosis model was prepared by intraperitoneal injection of 0.5% dimethylnitrosamine.At the same time, each group with intervention was administered with FAJ once a day for 8 weeks.The general morphology of rats was observed.The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), superoxide dismutase (SOD), malondialdehyde (MDA), hyaluronic acid (HA), and laminin (LN) were tested.The changes of liver in rats were observed via hematoxylin-eosin (HE) staining, and the expression of transforming growth factor-β1 (TGF-β1),tumor necrosis factor-α (TNF-α), matrix metalloproteinase-1 (MMP-1), tissue inhibitor of matrix metalloproteinase-1(TIMP-1) was detected using immunohistochemical methods.Results The levels of ALT, AST, MDA, HA, and LN in the serum of rats in the high and medium-dose of FAJ groups were lower than those in the model group, and the SOD levels were higher than those in the model group, the degree of inflammation and fibrosis of liver was better compared with that in the model group, the positive rates of expression of TGF-β1, TNF-α, TIMP-1 were lower than those of the model group, and the positive rates of expression of MMP-1 were higher than those of the model group, the differences were statistically significant (P<0.05).The serum levels of ALT, AST, MDA, and LN in rats in the low-dose of FAJ group were lower than those in the model group, and the differences were statistically significant (P<0.05).There were no significant differences in the levels of SOD or HA when compared with the model group (P>0.05).There were no significant differences in the degree of inflammation and fibrosis compared with the model group (P>0.05).There were no significant differences in the positive rates of expression of TGF-β1, TNF-α, MMP-1 or TIMP-1 compared with the model group (P>0.05).Conclusion The FAJ has protective effect on liver fibrosis in a dose-related manner.The mechanism may be related to protecting liver cells, reducing the degree of inflammation, preventing the occurrence of oxidative stress, inhibiting the activation of hepatic stellate cells, and decreasing the formation of extracellular matrix.
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