| The bark of betula platyphylla suk, contains betulinic acid and betulin. Since the anti-melanoma activity of betulinic acid was found in 1995 in Illinois University, Chicago, the pharmacological activity of it on other tumors has also been found, while it also showed a high activity on anti-HIV-1 infection. Both betulin and betulinic acid have the same pentacyclic triterpenoid skeleton, the former can be transformed into betulinic acid by oxidation and reduction reaction. Betulin and betulinic acid are triterpenes compounds with five member ring, they and their derivatives have anti-tumor and anti-HIV effects, the most potential efficacy is its anti-tumor effect. White birch is resourceful in the northeast of China, but the research on the pharmacological activity of betulin rarely reportes by domestic scholars.Objective: The aim of the study was to explore the effect of betulin on alcoholic liver disease in rats through observing biochemical indicators, from various aspects of alcoholic liver damage efficacy in rats, and discuss the relevant mechanism. Methods: Three days after adaptive feeding, 60 male SPF rats (body weight: 200-240 g) were randomly assigned into six groups by body weight (normal, low-dose, middle-dose, high-dose group, model and positive control groups). There were ten rats, the rats in the group has in normal group were fed by distilled water (9 ml·kg-1), and the rats in other groups were fed by gavage with 40% wine for 28 days, the model of alcohol liver disease in this way was built. After completion, the rats in the normal group were still fed by distilled water (9ml·kg-1).The doses of betulin solute in olive oil are: low-dose (10mg·kg-1); middle-dose (20mg·kg-1)and high-dose (40mg·kg-1), respectively , by gavage for 15 days.1 Effect of betulin on the body weight and organ indecesThe rats were weighed before the last gavage, and then obtained the changes in body weight during the experiment. At the end of the experiment, cardiac, liver, testis spleen and kidney were respectively weighed, and then the organ indeces were calculated. The results showed that as compared with that in the normal group, the changes in body weight of rats in the model group had significant difference (P < 0.05); while the changes in it in other groups also had significant difference (P< 0.05). compared with that in the model group, the changes in organ indeces of rats in normal group had significant difference (P < 0.05); while changes in organ index of rats in other groups have no significant difference (P> 0.05). Betulin can protect rats'organs from alcohol-induced liver injury, but after the result of organic lesions, we did not see significant changes in this experiment.2 Determination of serum ALT, AST, ALP, GGT, TG, CHO, HDLand LDLBlood was collected by eye removal and centrifugation, then the actives of ALT,ASTandALP and the levels of CHO,HDL and LDL were determinated with automatic biochemical analyzer.2.1 Effect of betulin on alcoholic liver injury in serum ALT, AST, ALP and GGT in ratsThe results showed that as compared with that in the model group, ALP and GGT activities in the low-dose group had significant difference (P < 0.01).As compared with that in the model group, ALT, AST, ALP and GGT activity in the medium-dose and high dose groups had significant difference (P < 0.01), which there are a clear dose-dependent manner in these indeces. So betulin can protect rat liver cells, stabilize structure of liver cells from alcohol-induced liver injury.2.2 Effect of betulin on alcoholic liver injury in serum CHO,LDL and HDL in ratsThe results showed that as compared with that in the model group, CHO content in the high-dose group had significant difference (P < 0.05); while LDL and HDL contents had no significant difference. So betulin can promote cholesterol metabolism and have a protective effect on the liver.2.3 Effect of betulin on alcoholic liver injury in serum and liver TG in rats The results showed that as compared with the model group, TG content in liver tissue in the middle-dose group had significant difference (P < 0.05). As compared with the model group, TG content in serum in the high-dose group had significant difference (P < 0.05); as compared with the model group, TG content in liver tissue also had significant difference (P < 0.05). So betulin promote fat metabolism and can protect rats from alcohol-induced liver injury.3 Determination of SOD, GSH-Px and GST activities and content of GSH, MDA in liver tissue3.1 Effect of betulin on alcoholic liver injury in liver SOD,GSH-PX and GST in ratsThe results showed that as compared with the model group, GSH-PX and GST activity in the positive control group (Yiganling group) had significant difference (P < 0.05); SOD activities also had significant difference (P < 0.01). As compared with the model group, SOD and GSH-PX activities in the high-dose group had significant difference (P < 0.01); GST activity also had significant difference (P < 0.05). So betulin has the ability to remove free radical and anti-lipid peroxidation, and can protect rats from alcohol-induced liver injury.3.2 Effect of betulin on Alcoholic liver injury in liver GSH and MDA in ratsThe results showed that as compared with the model group, GSH content in the positive control group (Yiganling group) had significant difference (P < 0.01); while MDA content also had significant difference (P< 0.05). As compared with the model group, GSH content in the high-dose group also had significant difference (P < 0.05); while MDA content also has significant difference (P< 0.05). So betulin can enhance detoxification of alcohol in liver, protect liver cells, stabilize membrane structure of liver cells; meanwhile it also has the ability to remove free radical and anti-lipid peroxidation, and can protect rats from alcohol-induced liver injury.4 Pathological changes in liver tissueNormal liver tissue of rat has a normal structure, liver cells aligned and lobular complete without hepatic steatosis necrosis or inflammation cell infiltrates. But in the model group, liver tissue pathology badly damaged, the liver cell cytoplasm markedly swollen, cytoplasm osteoporosis, lipid drops of different size and number with ballooning degeneration and edema can be seen in cytoplasm; the lobular structure disarranged with blot-shaped necrosis. Betulin can alleviate pathological damage on liver tissue and these obvioussymptoms, and there is obvious dose response relation in it, lobular structure in the high-doses group is normal.Conclusion: On the basis of our study, we believe that betulin can reduce serum levels of ALT, AST, ALP and GGT activities and CHO, TG contents and improve the content of LDL, promote fat metabolism in liver and remove free radical production.Thereby betulin can inhibit lipid peroxidation, reduce free radical damage, protect the liver cell structure and function, and ultimately protect the liver cells, stabilize the membrane structure and function, improve liver function status. Betulin can remove the ability of free radical, enhance SOD, GSH-PXand GST activities and GSH content and lower MDA content in liver, inhibit free radical-mediated lipid peroxidation of liver injury, protect liver cell structure and function, and improve the body-dependent antioxidant systems. To sum up, we think betulin has certain protect effect on alcohol-induced liver injury.
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