Silybin is considered to be the main biologically active component of silymarin. Its oxidized derivative 2,3-dehydrosilybin typically occurs in silymarin in small, but non-negligible amounts (up to 3%). Here, we investigated in detail complex biological activities of silybin and 2,3-dehydrosilybin optical isomers. Antioxidant activities of pure stereomers A and B of silybin and 2,3-dehydrosilybin, as well as their racemic mixtures, were investigated by using oxygen radical absorption capacity (ORAC) and cellular antioxidant activity (CAA) assay. All substances efficiently reduced nitric oxide production and cytokines (TNF-α, IL-6) release in a dose-dependent manner. Multidrug resistance (MDR) modulating potential was evaluated as inhibition of P-glycoprotein (P-gp) ATPase activity and regulation of ATP-binding cassette (ABC) protein expression. All the tested compounds showed strong dose-dependent inhibition of P-gp pump. Moreover, 2,3-dehydrosilybin A (30 µM) displayed the strongest sensitization of doxorubicin-resistant ovarian carcinoma. Despite these significant effects, silybin B was the only compound acting directly upon P-gp in vitro and also downregulating the expression of respective MDR genes. This compound altered the expression of P-glycoprotein (P-gp, ABCB1), multidrug resistance-associated protein 1 (MRP1, ABCC1) and breast cancer resistance protein (BCRP, ABCG2). 2,3-Dehydrosilybin AB exhibited the most effective inhibition of acetylcholinesterase activity. We can clearly postulate that silybin derivatives could serve well as modulators of a cancer drug-resistant phenotype.

中文翻译：

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水飞蓟宾衍生物的多药耐药性调节活性及其抗炎潜力。

水飞蓟宾被认为是水飞蓟素的主要生物活性成分。它的氧化衍生物2,3-脱氢水飞蓟宾通常以少量但不可忽略的量（最多3％）存在于水飞蓟素中。在这里，我们详细研究了水飞蓟宾和2,3-脱氢水飞蓟宾旋光异构体的复杂生物活性。水飞蓟宾和2,3-脱氢水飞蓟宾的纯立体异构体A和B以及它们的外消旋混合物的抗氧化活性通过使用氧自由基吸收能力（ORAC）和细胞抗氧化活性（CAA）分析进行了研究。所有物质均以剂量依赖的方式有效减少了一氧化氮的产生和细胞因子（TNF-α，IL-6）的释放。评价多药耐药性（MDR）的调节潜力，以抑制P-糖蛋白（P-gp）ATPase活性和调节ATP结合盒（ABC）蛋白的表达。所有测试的化合物均显示出强烈的剂量依赖性P-gp泵抑制作用。此外，2,3-脱氢水飞蓟宾A（30 µM）对耐阿霉素的卵巢癌表现出最强的敏化作用。尽管有这些明显的作用，水飞蓟宾B是唯一在体外直接作用于P-gp并下调各个MDR基因表达的化合物。该化合物改变了P-糖蛋白（P-gp，ABCB1），多药耐药相关蛋白1（MRP1，ABCC1）和乳腺癌耐药蛋白（BCRP，ABCG2）。2,3-Dehydrosilybin AB表现出最有效的抑制乙酰胆碱酯酶活性。我们可以清楚地假设，水飞蓟宾衍生物可以很好地用作抗癌药物表型的调节剂。