| Description | Isosilybin (Isosilibinin) and Silybin might be suitable candidates to design potent PXR antagonists to prevent drug-drug interactions via CYP3A4 in cancer patients. |
| In vitro | 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]。 |
| Cell experiments | 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]. |
| Target activity | CYP3A4:74 μM. |
| Synonyms | Isosilybinin, Isosilibinin, 异水飞蓟宾, Silymarin, Silybin B, Q-100795 |
| molecular weight | 482.44 |
| Molecular formula | C25H22O10 |
| CAS | 72581-71-6 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 88 mg/mL(182.4 mM) Chloroform, Dichloromethane, Ethyl Acetate: Soluble |
| References | 1. Mooiman KD, et al. Milk thistle's active components silybin and isosilybin: novel inhibitors of PXR-mediated CYP3A4 induction. Drug Metab Dispos. 2013 Aug;41(8):1494-504. 2. Deep G, et al. Isosilybin B and isosilybin A inhibit growth, induce G1 arrest and cause apoptosis in human prostate cancer LNCaP and 22Rv1 cells. Carcinogenesis. 2007 Jul;28(7):1533-42. 3. Deep G, et al. Isosilybin B causes androgen receptor degradation in human prostate carcinoma cells via PI3K-Akt-Mdm2-mediated pathway. Oncogene. 2008 Jun 26;27(28):31986-98. 4. Pferschy-Wenzig EM, et al. Identification of isosilybin a from milk thistle seeds as an agonist of peroxisome proliferator-activated receptor gamma. J Nat Prod. 2014 Apr 25;77(4):842-7. |