水飞蓟宾的抗肿瘤、抗氧化和免疫调节分子药理学机制研究进展  

An updated review at molecular pharmacological level for the mechanism of anti-tumor,antioxidant and immunoregulatory action of silibinin

作　　者：王红军[1] 姜媛媛 路平[1] 王琼[1] 池岛乔[1] 

机构地区：[1]沈阳药科大学中日医药研究所,辽宁沈阳110016

出　　处：《药学学报》2010年第4期413-421,共9页Acta Pharmaceutica Sinica

摘　　要：水飞蓟宾(silibinin)来源于菊科植物水飞蓟(Silybum marianum),为黄酮木脂素类化合物,具有明显抗氧化和抗炎的特性,临床上作为保肝药物长期应用于中国、德国和日本等国家。近年来发现水飞蓟宾有明显的抗肿瘤活性,其主要机制为抑制肿瘤受体型酪氨酸激酶(receptor tyrosine kinase,RTK)的活性,如抑制表皮生长因子受体1(epidermal growth factor receptor1,EGFR)和胰岛素样生长因子1受体(insulin-like growth factor1receptor,IGF-1R)及其下游信号分子的活化。同时因为发现水飞蓟宾对羟自由基(?OH)的选择性清除,以及对核因子κB(nuclear factor-κB,NF-κB)的特异性抑制,使其抗氧化和抗炎的分子机制更为明确。一些新的发现如水飞蓟宾通过抑制氧化应激和炎症反应而改善β-淀粉样蛋白(amyloidβprotein,Aβ)引起的认知功能障碍等对拓展水飞蓟宾的药用前景具有重要价值。本文对水飞蓟宾的分子药理机制进行总结,主要从水飞蓟宾抑制肿瘤RTK信号转导、抗氧化与自由基清除、调节免疫与炎症3个方面进行了阐述。Silibinin,from milk thistle （Silybum marianum）,is a flavonolignan with anti-oxidative and anti-inflammatory properties. It has been therapeutically used for the treatment of hepatic diseases in China,Germany and Japan. Recently,increasing evidences prove that silibinin is also a potent antitumor agent,and the major anti-tumor mechanism for silibinin is the prominent inhibition of the activities of receptor tyrosine kinases （RTKs） and their downstream signal molecules in a variety of tumor cell lines,such as epidermal growth factor receptor 1 （EGFR） and insulin-like growth factor 1 receptor （IGF-1R） signaling pathways. Meanwhile,the evidences that silibinin selectively scavenges hydroxyl free radical （？OH） and specifically inhibits the action of nuclear factor κB （NF-κB） provide more complicated explanations for its antioxidant and anti-inflammatory effects. Some new findings such as that silibinin attenuating the cognitive deficits induced by amyloid β protein （Aβ） peptide through its antioxidative and anti-inflammatory properties is valuable to broad the medical prospect of silibinin. In this review,we discuss the molecular pharmacological mechanisms of silibinin,focusing on its inhibition of tyrosine kinases,actions of antioxidation,free radical scavenging,immunoregulation and anti-inflammation.

关 键 词：水飞蓟宾 酪氨酸激酶 抗氧化 免疫调节 

分 类 号：R285[医药卫生—中药学]