Amalia Reski, Ohama Takashi, Parhar Ishwar Singh, Airin Claude Mona, Sato Hiroshi, Budiyanto Agung, Astuti Pudji
Faculty of Veterinary Medicine, Gadjah Mada University, Yogyakarta, Indonesia.
Department of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan.
Open Vet J. 2025 Apr;15(4):1663-1672. doi: 10.5455/OVJ.2025.v15.i4.18. Epub 2025 Apr 30.
Testosterone is a vital androgen hormone responsible for sex differentiation, producing male sex characteristics, spermatogenesis, and fertility. Abnormalities in testosterone levels, leading to reduced weight gain and reproductive capacity, pose a significant problem for livestock farmers. Although synthetic testosterone injection is a general strategy to restore hormone levels, it leads to the downregulation of testosterone production in livestock. Therefore, an alternative method that does not affect the safety of livestock products is needed. Studies have shown that abnormal conversion from testosterone to estradiol (aromatization) causes high levels of estradiol in male animals. In this study, we analyzed the aromatase blocker activity of I3C extracted from the stem part of broccoli, which has beneficial effects on the reproductive system via unknown molecular mechanisms.
This study aimed to explore the potential of I3C as an aromatase blocker using and approaches.
Biological activity was predicted using PASS Online, and toxicity was assessed using Protox-3. Drug-likeness was determined using Lipinski's Rule of Five using SWISS ADME. Molecular docking simulations in PyRx 0.8 analyzed binding interactions with CYP19, CYP1A1, and CYP1B1, using LigPlot for amino acid interactions and PyMOL for visualization. Molecular dynamics simulations were used to assess the binding stability over time. Broccoli was freeze-dried, blended, and analyzed for I3C using thin-layer chromatography. Male Sprague-Dawley rats were used to measure CYP19 levels, and blood samples were analyzed using the ELISA method.
I3C met the criteria as a drug candidate, binding to CYP19, CYP1A1, and CYP1B1 at the active site with similar poses and good affinity of -5.8, -7.8, and -8.2, respectively. However, the binding affinity was not as strong as that of the control (Alpha-Naphthoflavone), and the formed bonds were unstable. Consistent with the results, the CYP19 concentrations in the letrozole and broccoli powder groups were not significantly different.
I3C can influence CYP19 expression, suggesting its potential as an aromatase-blocking agent. However, further research is required to gain a comprehensive understanding of its effects.
睾酮是一种重要的雄激素，负责性别分化、产生男性性征、精子发生和生育能力。睾酮水平异常会导致体重增加和生殖能力下降，这给牲畜养殖户带来了重大问题。尽管注射合成睾酮是恢复激素水平的常用策略，但它会导致牲畜体内睾酮生成的下调。因此，需要一种不影响畜产品安全性的替代方法。研究表明，睾酮向雌二醇的异常转化（芳香化）会导致雄性动物体内雌二醇水平升高。在本研究中，我们分析了从西兰花茎部提取的异硫氰酸酯（I3C）的芳香化酶阻断活性，其通过未知分子机制对生殖系统具有有益作用。
本研究旨在使用[具体方法1]和[具体方法2]方法探索I3C作为芳香化酶阻断剂的潜力。
使用在线PASS预测生物活性，并使用Protox - 3评估毒性。使用SWISS ADME根据Lipinski的五规则确定药物相似性。在PyRx 0.8中进行分子对接模拟，分析与细胞色素P450 19（CYP19）、细胞色素P450 1A1（CYP1A1）和细胞色素P450 1B1（CYP1B1）的结合相互作用，使用LigPlot分析氨基酸相互作用，并使用PyMOL进行可视化。使用分子动力学模拟评估随时间的结合稳定性。将西兰花冷冻干燥、研磨，并使用薄层色谱法分析I3C。使用雄性Sprague - Dawley大鼠测量CYP19水平，并使用酶联免疫吸附测定（ELISA）方法分析血液样本。
I3C符合作为候选药物的标准，以相似的构象与CYP19、CYP1A1和CYP1B1的活性位点结合，亲和力分别为 - 5.8、 - 7.8和 - 8.2，亲和力良好。然而，其结合亲和力不如对照（α - 萘黄酮）强，形成的键不稳定。与[具体实验]结果一致，来曲唑组和西兰花粉末组中的CYP19浓度无显著差异。
I3C可影响CYP19表达，表明其作为芳香化酶阻断剂的潜力。然而，需要进一步研究以全面了解其作用。
