Laboratory of Biotransformation, Institute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, 142 20 Prague, Czech Republic.
Int J Mol Sci. 2021 Jul 23;22(15):7885. doi: 10.3390/ijms22157885.
This review focuses on the specific biological effects of optically pure silymarin flavo-nolignans, mainly silybins A and B, isosilybins A and B, silychristins A and B, and their 2,3-dehydro derivatives. The chirality of these flavonolignans is also discussed in terms of their analysis, preparative separation and chemical reactions. We demonstrated the specific activities of the respective diastereomers of flavonolignans and also the enantiomers of their 2,3-dehydro derivatives in the 3D anisotropic systems typically represented by biological systems. In vivo, silymarin flavonolignans do not act as redox antioxidants, but they play a role as specific ligands of biological targets, according to the "lock-and-key" concept. Estrogenic, antidiabetic, anticancer, antiviral, and antiparasitic effects have been demonstrated in optically pure flavonolignans. Potential application of pure flavonolignans has also been shown in cardiovascular and neurological diseases. Inhibition of drug-metabolizing enzymes and modulation of multidrug resistance activity by these compounds are discussed in detail. The future of "silymarin applications" lies in the use of optically pure components that can be applied directly or used as valuable lead structures, and in the exploration of their true molecular effects.
本综述重点关注光学纯水飞蓟素黄酮木脂素，主要是水飞蓟宾 A 和 B、异水飞蓟宾 A 和 B、水飞蓟亭 A 和 B 及其 2,3-脱氢衍生物的特定生物学效应。还讨论了这些黄酮木脂素的手性，包括它们的分析、制备分离和化学反应。我们展示了黄酮木脂素的各个非对映异构体以及它们的 2,3-脱氢衍生物的对映异构体在典型的生物体系代表的 3D 各向异性体系中的特定活性。在体内，水飞蓟素黄酮木脂素不作为氧化还原抗氧化剂，而是根据“锁钥”概念发挥生物靶标的特定配体的作用。已证明光学纯黄酮木脂素有雌激素、抗糖尿病、抗癌、抗病毒和抗寄生虫作用。纯黄酮木脂素在心血管和神经疾病中的潜在应用也得到了展示。详细讨论了这些化合物对药物代谢酶的抑制作用和多药耐药活性的调节。“水飞蓟素应用”的未来在于使用可直接应用或用作有价值的先导结构的光学纯成分，并探索其真正的分子作用。
