Isosilybin 是一种类黄酮，来源于乳蓟；能够抑制CYP3A4诱导(IC50:74 μM)。

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

The reporter gene assay shows that milk thistle’s components silybin and isosilybin are responsible for the inhibition of PXR-mediated CYP3A4 induction by milk thistle. The isomer isosilybin is a stronger inhibitor of PXR-mediated CYP3A4 induction compared with silybin. A solution of 89, 133, and 200 μM isosilybin significantly inhibits CYP3A4 induction by 64, 82, and 88%, respectively. Isosilybin inhibits CYP3A4 induction with an IC50 of 74 μM[1]. Isosilybin B and isosilybin A, two diastereoisomers isolated from silymarin, have anti-prostate cancer (PCA) activity that is mediated via cell cycle arrest and apoptosis induction. Isosilybin B and isosilybin A treatment results in growth inhibition and cell death together with a strong G(1) arrest and apoptosis in human prostate cancer LNCaP and 22Rv1 cells[2]. Isosilybin B causes increased phosphorylation of Akt (Ser-473 and Thr-308) and Mdm2 (Ser-166), which is linked with androgen receptor degradation as pretreatment with PI3K inhibitor (LY294002)-restored androgen receptor level. Isosilybin B treatment enhances the formation of complex between Akt, Mdm2 and AR, which promotes phosphorylation-dependent AR ubiquitination and its degradation by proteasome[3]. Isosilybin A is able to significantly activate PPARγ at a concentration of 30 μM (2.08±0.48 fold, p<0.01). Isosilybin A causes transactivation of a PPARγ-dependent luciferase reporter in a concentration-dependent manner. In silico docking studies suggests a binding mode for 3 distinct from that of the inactive silymarin constituents, with one additional hydrogen bond to Ser342 in the entrance region of the ligand-binding domain of the receptor[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].

72581-71-6

C25H22O10

482.441

Isosilibinin;Isosilybinin;Silymarin;异水飞蓟宾;Q-100795;Silybin B

DMSO:88 mg/mL(182.4 mM)
Chloroform, Dichloromethane, Ethyl Acetate:Soluble
Powder: -20°C for 3 years
In solvent: -80°C for 2 years