Isosilybin (Isosilibinin) and Silybin might be suitable candidates to design potent PXR antagonists to prevent drug-drug interactions via CYP3A4 in cancer patients.

CYP3A4:74 μM.

报告基因检测表明，奶蓟的成分silybin和isosilybin负责抑制奶蓟对PXR介导的CYP3A4诱导的抑制作用。与silybin相比，异构体isosilybin对PXR介导的CYP3A4诱导具有更强的抑制作用。89, 133和200 μM的isosilybin溶液分别可以显著抑制CYP3A4诱导64, 82和88%。isosilybin以IC50 为74 μM抑制CYP3A4诱导[1]。从水飞蓟中分离的两种对映异构体isosilybin B和isosilybin A具有通过细胞周期阻滞和诱导凋亡介导的抗前列腺癌（PCA）活性。isosilybin B和isosilybin A处理导致人类前列腺癌LNCaP和22Rv1细胞的生长抑制和细胞死亡，伴随着强烈的G(1)期阻滞和凋亡[2]。isosilybin B导致Akt（Ser-473和Thr-308）和Mdm2（Ser-166）的磷酸化增强，这与雄激素受体降解有关，以PI3K抑制剂（LY294002）预处理恢复雄激素受体水平。isosilybin B处理促进了Akt、Mdm2和AR之间复合物的形成，这促进了依赖磷酸化的AR泛素化及其通过蛋白酶体的降解[3]。在30 μM浓度下，isosilybin A能显著激活PPARγ（2.08±0.48倍，p<0.01）。isosilybin A引起PPARγ依赖性萤光素酶报告基因的浓度依赖性转录激活。体内模拟对接研究表明，与无活性的水飞蓟成分相比，3的结合模式不同，它在受体配体结合域的入口区域额外形成一个与Ser342的氢键[4]。

LNCaP cells and 22Rv1 cells are plated and treated at 40–50% confluency with different doses of isosilybin B and isosilybin A (10–90 μM in medium) dissolved originally in Dimethyl sulfoxide (DMSO) for the desired time periods (24–48 h) in serum condition. An equal amount of DMSO (vehicle) is present in each treatment, including control; DMSO concentration did not exceed 0.1% (v/v) in any treatment. At the end of desired treatments, total cell number is determined by counting each sample in duplicate using a hemocytometer under an inverted microscope. Cell viability is determined using trypan blue exclusion method[2].