Effect of lesimarin against thioacetamide-induced liver cirrhosis in rat

Liver cirrhosis is one of chronic liver diseases with high disability and mortality accompanying fibrosis, hepatocyte damage, and liver dysfunction. In this study, the hepatoprotective and the antifibrotic properties of lesimarin(lecithin - silymarin - Artemisia messerschmitiana Besser(AMB) extract complex at 11:3:6 ratio) on rat hepatic fibrosis induced by thioacetamide (TAA) was investigated. Rats were divided into seven groups: control, lesimarin, TAA, TAA+lesimarin, TAA+lecithin, TAA+silymarin, TAA+AMB. Rats were administered with TAA at a dose of 200 mg/kg body weight intraperitoneally twice a week for three months. Lesimarin, lecithin, silymarin and AMB were administered at a dose of 1.0, 1.0, 0.5, 1.0g/kg body weight orally daily for three months, respectively. TAA administration resulted in hepatic fibrosis, significant decrease in body weight, albumin level and A/G ratio and increase in plasma transaminase, GGT(γ-glutamyltransferase) and ALP(alkaline phosphatase) activities as well as hepatic hydroxyproline content, which were attenuated by lesimarin administration. Lesimarin was found to decrease AST, ALT and GGT, ALP and bilirubin, hydroxyproline levels and increase albumin level and A/G ratio and its effect is more prominent than those of individual constituents. These results suggest this new drug, lesimarin, might be a promising drug to be used for chronic liver diseases.

肝硬化是一类伴随纤维化、肝细胞损伤及肝功能障碍的高致残率、高死亡率慢性肝病。本研究探讨了莱斯马林（lesimarin，即卵磷脂-水飞蓟素-密花蒿（Artemisia messerschmitiana Besser, AMB）提取物复合物，配比为11:3:6）对硫代乙酰胺（thioacetamide, TAA）诱导的大鼠肝纤维化的保肝及抗纤维化作用。
实验将大鼠分为7组：正常对照组、莱斯马林单独给药组、TAA模型组、TAA+莱斯马林干预组、TAA+卵磷脂组、TAA+水飞蓟素组、TAA+AMB提取物组。TAA以200 mg/kg体重的剂量腹腔注射，每周2次，持续3个月。莱斯马林、卵磷脂、水飞蓟素及AMB提取物分别以1.0、1.0、0.5、1.0 g/kg体重的剂量每日经口灌胃，持续3个月。
TAA给药可诱导大鼠发生肝纤维化，表现为体重显著降低、血清白蛋白水平及白蛋白/球蛋白（A/G）比值下降，同时血浆转氨酶、γ-谷氨酰转移酶（γ-glutamyltransferase, GGT）、碱性磷酸酶（alkaline phosphatase, ALP）活性及肝组织羟脯氨酸含量升高，而莱斯马林给药可缓解上述病理变化。
研究发现，莱斯马林可降低天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、GGT、ALP及胆红素水平与肝组织羟脯氨酸含量，同时升高血清白蛋白水平及A/G比值，且其干预效果优于各单一成分。
上述结果表明，这款新型复方制剂莱斯马林有望成为治疗慢性肝病的潜在候选药物。