The Pharmacodynamic Effects And Mechanisms Of Compound Phyllanthus Urinsria â…¡ On Carbon Tetrachloride Induced Acute Liver Injury Or Liver Fibrosis In Rodents

ObjectTo screen various ways of extraction of Compound Phyllanthus Urinsria â…¡ (CPU â…¡) for the optimum one with best hepatic protective outcome. To observe protective or therapeutic effects of CPU II on carbon-tetrachloride(CCl4)-mediated acute liver injury in mice or carbon-tetrachloride(CCl4)-mediated liver fibrosis in rats.Methods(1) 84 mice were randomized into 7 groups and received administration of normal saline solution as normal or model control, bifendate as positive control, different ways of extraction and doses of CPU II, which were normal doses of granule No.1, No.2, No.3 and high dose of granule No.3, respectively for 7 days. All mice except those of normal control were then received an injection of 0.12% CCl4 to be induced acute liver injury. Mice were sacrificed in 16h. Serum alanine aminotransferase (ALT) were measured afterwards to investigate the optimum way of extraction of CPU â…¡ with best hepatic protective effects. The optimum granule of CPU II were then chosen to be evaluated the hepatic protective effects in a further degree.(2) 72 mice were divided randomly into 6 groups and received administration of normal saline solution as normal or model control, bifendate as positive control, high, medium or low doses of CPU II respectively for 7 days. All mice except those of normal control were then received an injection of 0.12% CCl4 to be induced acute liver injury. Mice were sacrificed in 16h. Hepatic tissues for hematoxylin-eosin (HE) staining were collected and levels of serum ALT, aspartate aminotransferase (AST) or tissue superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH) were measured afterwards.(3) 50 rats were randomized into 5 groups. Except for the ones as normal control, all rats were received injections of 50% CCl4 once per triduum for 8 weeks to be induced liver fibrosis. Each group of rats were received administration of normal saline solution as normal or model control, Fuzheng Huayu capsule as positive control, high or medium doses of CPU II granule No.3 respectively from the 5th week after the first injection. Rats were sacrificed at the end of the 8th week. The exterior health status was observed, levels of serum ALT, AST, hyaluronic acid (HA), total bilirubin (TBIL), total bile acid (TBA) were measured. Hepatic tissues were collected and stained with HE, or Picro-Sirius methods for grading fibrosis stage.Results(1) Significant effect (P<0.05) of decreasing level of ALT was shown in comparison with model control after the administration of CPU â…¡ granule No.3 of which was the extracting procedure purifying after alcohol extraction.(2) Protective effects on CCl4 induced acute liver injury in mice were shown by further study with CPU â…¡ granule No.3 that compared with model control, hepatic histopathologic changes alleviated with the administration of CPU â…¡, levels of serum ALT, AST and tissue MDA decrease and levels of tissue GSH, SOD increase with the administration of high dose of CPU â…¡ (P<0.05).(3) In comparison with model control, alleviated liver fibrosis and hepatitis activity were shown with the administration of high dose of CPU â…¡ granule No.3 on CCl4 induced chronic liver injury in rats, accompanied with decreased levels of serum ALT, AST, TBA, TBIL and HA, while no significant difference were shown.Conelusion(1) Protective effects of CPU â…¡ on CCl4-induced acute liver injury were shown, the mechanism of which was convinced to be related to the protective effects on lipid peroxidation.(2) Mild therapeutic effects of CPU â…¡ were shown on CCl4-induced chronic liver injury and liver fibrosis. Further study is required for confirmation.