Abstract：
Parabens are commonly used preservatives in cosmetics, food, and pharmaceutical products. The objective of this study was to examine the effect of nine parabens on human and rat 17β-hydroxysteroid dehydrogenase 1 (17β-HSD1) in human placental and rat ovarian cytosols, as well as on estradiol synthesis in BeWo cells. The results showed that the IC50 values for these compounds varied from methylparaben with the weakest inhibition (106.42 μM) to hexylparaben with the strongest inhibition (2.05 μM) on human 17β-HSD1. Mode action analysis revealed that these compounds acted as mixed inhibitors. For rats, the IC50 values ranged from the weakest inhibition for methylparaben (no inhibition at 100 μM) to the most potent inhibition for hexylparaben (0.87 μM), and they functioned as mixed inhibitors. Docking analysis indicated that parabens bind to the region bridging the NADPH and steroid binding sites of human 17β-HSD1 and the NADPH binding site of rat 17β-HSD1. Bivariate correlation analysis demonstrated negative correlations between LogP, molecular weight, heavy atoms, and apolar desolvation energy, and the IC50 values of these compounds. In conclusion, this study identified the inhibitory effects of parabens and their binding mechanisms on human and rat 17β-HSD1, as well as their impact on hormone synthesis.
摘要：
对羟基苯甲酸酯是化妆品中常用的防腐剂，食物,和医药产品。这项研究的目的是检查九种对羟基苯甲酸酯对人和大鼠17β-羟基类固醇脱氢酶1（17β-HSD1）在人胎盘和大鼠卵巢细胞溶胶中的作用，以及BeWo细胞中雌二醇的合成。结果表明，这些化合物的IC50值从对人17β-HSD1的抑制作用最弱的对羟基苯甲酸甲酯（106.42μM）到抑制作用最强的对羟基苯甲酸己酯（2.05μM）不等。模式作用分析表明，这些化合物充当混合抑制剂。对老鼠来说,IC50值范围从对羟基苯甲酸甲酯的最弱抑制作用（100μM时无抑制作用）到对羟基苯甲酸己酯的最有效抑制作用（0.87μM），它们起混合抑制剂的作用。对接分析表明，对羟基苯甲酸酯结合到桥接人17β-HSD1的NADPH和类固醇结合位点以及大鼠17β-HSD1的NADPH结合位点的区域。双变量相关分析表明LogP之间呈负相关，分子量,重原子,和非极性去溶剂化能量，和这些化合物的IC50值。总之,这项研究确定了对羟基苯甲酸酯的抑制作用及其对人和大鼠17β-HSD1的结合机制，以及它们对激素合成的影响。
