Gazák Radek, Walterová Daniela, Kren Vladimír
Laboratory of Biotransformation, Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídezská 1083, CZ-142 20 Prague, Czech Republic.
Curr Med Chem. 2007;14(3):315-38. doi: 10.2174/092986707779941159.
This review critically surveys the literature published mainly within this millennium on the new and emerging applications of silybin (pure, chemically defined substance) and silymarin (flavonoid complex from Silybum marianum - milk thistle seeds). These compounds used so far mostly as hepatoprotectants were shown to have other interesting activities, e.g. anticancer and canceroprotective and also hypocholesterolemic activity. These effects were demonstrated in a large variety of illnesses of different organs, e.g. prostate, lungs, CNS, kidneys, pancreas and also in the skin protection. Besides the cytoprotective activity of silybin mediated by its antioxidative and radical-scavenging properties also new functions based on the specific receptor interaction were discovered. These were studied on the molecular level and modulation of various cell-signaling pathways with silybin was disclosed--e.g. NF-kappaB, inhibition of EGFR-MAPK/ERK1/2 signaling, activity upon Rb and E2F proteins, IGF-receptor signaling. Proapoptotic activity of silybin in pre- and/or cancerogenic cells and anti-angiogenic activity of silybin are other important findings that bring silymarin preparations closer to respective application in the cancer treatment. Discovery of the inhibition and modulation of drug transporters, P-glycoproteins, estrogenic receptors, nuclear receptors by silybin and some of its new derivatives contribute further to the better understanding of silybin activity on the molecular level. Silymarin application in veterinary medicine is reviewed as well. Recent works using optically pure silybin diastereomers clearly indicate extreme importance of the use of optically active silybin namely in the receptor studies. Significance of silymarin and its components in the medicine is clearly indicated by an exponential growth of publications on this topic--over 800 papers in the last 5 years.
本综述批判性地审视了主要在本千年内发表的关于水飞蓟宾（纯的、化学定义明确的物质）和水飞蓟素（来自水飞蓟——奶蓟种子的黄酮类化合物复合物）新的和正在出现的应用的文献。这些化合物迄今为止大多用作肝脏保护剂，已显示出具有其他有趣的活性，例如抗癌、防癌以及降胆固醇活性。这些作用在多种不同器官的疾病中得到证实，如前列腺、肺、中枢神经系统、肾脏、胰腺，也体现在皮肤保护方面。除了水飞蓟宾通过其抗氧化和自由基清除特性介导的细胞保护活性外，还发现了基于特定受体相互作用的新功能。这些在分子水平上进行了研究，并揭示了水飞蓟宾对各种细胞信号通路的调节作用——例如核因子κB、对表皮生长因子受体 - 丝裂原活化蛋白激酶/细胞外信号调节激酶1/2信号传导的抑制、对视网膜母细胞瘤蛋白和E2F蛋白的作用、胰岛素样生长因子受体信号传导。水飞蓟宾在癌前和/或致癌细胞中的促凋亡活性以及水飞蓟宾的抗血管生成活性是其他重要发现，这些发现使水飞蓟素制剂在癌症治疗中的应用更接近实际。水飞蓟宾及其一些新衍生物对药物转运体、P - 糖蛋白、雌激素受体、核受体的抑制和调节作用的发现，进一步有助于在分子水平上更好地理解水飞蓟宾的活性。本文还综述了水飞蓟素在兽医学中的应用。最近使用光学纯的水飞蓟宾非对映异构体的研究清楚地表明了使用光学活性水飞蓟宾在受体研究中的极端重要性。关于该主题的出版物呈指数增长——过去五年超过800篇论文，清楚地表明了水飞蓟素及其成分在医学中的重要性。
