Effects of silibinin in improving liver function of rats with alcoholic fatty liver / 中国组织工程研究

ABSTRACT

BACKGROUND: Silibinin has broad pharmaceutical effects, such as anti-free radicals, anti-lipid peroxidation, anti-lipoid oxidase, anti-glutathione (GSH) depletion, anti-neoplastic and serum lipid-lowering effects. Clinically, silibinin is often used in treating alcoholic liver disease. OBJECTIVE: To investigate the pharmacological mechanism of silibinin for alcoholic fatty liver in rats. DESIGN: Randomized and controlled study.SETTING: Guangzhou Hospital of Traditional Chinese Medicine.MATERIALS The experiment was conducted at the Animal Experimental Laboratory of Guangdong Pharmaceutical Institute from August to October 2003. Totally 57 SD rats, without unusual bacteria, weighting (150±10)g and of either gender, were selected. Yiganling tablets containing 38.5 mg silibinin were produced by Zhuzhou No.3 Pharmaceutical Factory (Batch No. 20020808).METHODS: Among the 57 SD rats, 18 rats were regarded as normal control group. Rats in normal control group were administered with normal saline by gavage, and fed with normal food and distilled water in place of alcohol for 10 weeks. Rats in model group and silibinin group were fed with high-calorie food and 100 mL/L alcohol for 6 weeks to establish model of rat alcoholic fatty liver. The other rats were divided into model control group (n=18) and silibinin group (n=21). Rats in model control group were treated with distilled water while those in silibinin group were treated with 100 mg/kg silibinin. Meanwhile, 100 mL/L ethanol and hyperalimentation feed were given for 4 weeks. After animals were killed, TG, SOD, GSH and MDA levels were measured with liver suspension.MAIN OUTCOME MEASURES: Contents of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), tumor necrosis factor (TNF)-α , and transforming growth factor (TGF)-β1.RESULTS: All the 57 rats entered the final analysis. Silibinin could inhibit the activities of serum AST, ALT and AKP [(2 550.5±400.1), (533.4±100.0), (2 217.1±750.2)nkat/L], and the differences were significant as compared with those in model control group [(3 600.7±666.8), (800.2±100.0), (2 900.6±1 333.6) nkat/L, P ＜ 0.05-0.01]. Contents of TG, LDL-C, TNF-α and TGF-β1 in silibinin group [(1.8±0.8), (0.17±0.04), (6.66±1.38), (24.1±4.1) mmol/L] were lower than those in model group [(2.8±1.4), (0.20±0.05), (7.81±1.06), (28.8±6.3) mmol/L] with significant differences (P ＜ 0.05-0.01). Silibinin could increase the content of HDL-C but decrease the contents of TG and MDA (P ＜ 0.05-0.01), and improve SOD activity as well as hepatocyte and fatty degeneration (P ＜ 0.01).However, it had no obvious effect on the content of reduced estathion (P ＞ 0.05).CONCLUSION: Silibinin can inhibitthe formation of alcoholic fatty liver in rats. The pharmacological mechanism of silibinin may involve anti-oxidation, removing free radicals, inhibiting lipid peroxidation, regulating blood lipid component, reducing fatty sediment in liver, and anti-immunoinflammation and anti-hyperplasia effects.