Ophiopogonin-D

Ophiopogonin D is a natural product,and is a CYP2J3 inducer that significantly inhibits Ang II induced NF-κB nuclear translocation. Ophiopogonin-D significantly inhibited the in vitro and in vivo growth of prostate cells via RIPK1. Ophiopogonin-D may be developed as a potential anti-prostate cancer agent.

Ophiopogonin D(OPD) was shown to exert potent anti-tumor activity against PC3 cells.?It induced apoptosis via a RIPK1-related pathway, increased the protein expression levels of RIPK1 and Bim, and decreased the levels of cleaved-RIPK1, caspase 8, cleaved-caspase 8, Bid, caspase 10, and cleaved-caspase 10.?OPD' also increased the mRNA expression of Bim.?The protein expression of Bim was decreased when cells were pre-treated with necrostatin-1[1].
OPHIOPOGONIN D(OP-D) significantly inhibited Ang II induced NF-κB nuclear translocation, IκBα down-regulation and activation of pro-inflammatory cytokines (TNF-α, IL-6 and VCAM-1) by increasing the expression of CYP2J2/EETs and PPARα in HUVECs.?Furthermore, treatment with exogenous 11,12-EET attenuated endothelial inflammation induced by Ang II as evidenced by inhibited NF-κB nuclear translocation, increased IκBα expression and decreased inflammation factor level.?Finally, the activation of NF-κB nuclear translocation induced by Ang II was also markedly suppressed by fenofibrate.?Co-incubation with 6-(2-proparglyloxyphenyl) hexanoic acid (PPOH) and PPARα inhibitor GW6471 before drug treatment abolished the endothelium protective effects of OP-D.?Suggest that OP-D has the endothelial protective effect through activation of CYP2J and increasing EETs, and PPARα involves in this process.

Ophiopogonin D(OPD)′ treatment led to significant tumor growth inhibition at a dose of 5.0 mg/kg bodyweight, beginning on Day 6 of treatment (p = 0.034).?At the end of the study (Day 24), the tumor tissues were excised, photographed, and weighed.?Treatment with 5.0 mg/kg bodyweight OPD′ resulted in significant (p = 0.000) tumor growth inhibition by approximately 79.8% on Day 24 compared to the vehicle treatment.?The 5.0 mg/kg dose led to significantly stronger tumor growth inhibition than the 2.5 mg/kg dose (p = 0.000).?There was not a significant loss of body weight in any of the groups[1].

The CCK-8 assay was used to assess the viability of prostate cancer cells.?The cell morphology was examined by an ultrastructural analysis via transmission electron microscopy.?Cells in apoptosis (early and late stages) were detected using an Annexin V-FITC/propidium iodide kit with a FACSCaliber flow cytometer.?JC-1, a cationic lipophilic probe, was employed to measure the mitochondrial membrane potential (MMP) of PC3 cells.?Changes in the protein expression of RIPK1, C-RIPK1, caspase 8, cleaved-caspase 8, Bim, Bid, caspase 10, and cleaved-caspase 10 were evaluated by Western blotting.?The mRNA expression of Bim was examined by quantitative real-time reverse transcription polymerase chain reaction.?Z-VAD-FMK (a caspase inhibitor) and necrostatin-1 (a specific inhibitor of RIPK1) were utilized to determine whether the cell death was mediated by RIPK1 or caspases[1].

One week after tumor cell inoculation, mice bearing palpable tumors were randomly divided into control and treatment groups (8 mice/group).?OPD′ was dissolved in the vehicle, PEG400:Saline:Ethanol (400:300:200, v/v/v), and administered (via i.p. injection) at doses of 2.5 or 5.0 mg/kg bodyweight 5 days a week for 24 days.?The control group received vehicle only.?The mice were sacrificed by cervical dislocation on Day 24, and the tumor tissues were removed and weighed[1].

DMSO: 30 mg/mL (35.09 mM), Sonication is recommended.

10% DMSO+90% Corn Oil: 2 mg/mL (2.34 mM)