Center of Scientific Research, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Neurochem Int. 2017 Nov;110:84-90. doi: 10.1016/j.neuint.2017.09.010. Epub 2017 Sep 22.
Apigenin, a common flavonoid, has extensive pharmacological activities. Apigenin inhibits some steroid biosynthetic enzymes, suggesting that it may block neurosteroid synthesis. Neurosteroids play many important roles in neurological functions. The objective of the present study is to investigate effects of apigenin on neurosteroidogenic enzymes, 5α-reductase 1 (SRD5A1), 3α-hydroxysteroid dehydrogenase (AKR1C9), and retinol dehydrogenase 2 (RoDH2), in rats. SRD5A1, AKR1C9, and RoDH2 were expressed in COS-1 cells and the effects of apigenin on these enzymes and modes of action were explored using radiolabeled substrates and thin-layer chromatographic separation coupled with radiometry. Apigenin inhibited SRD5A1, AKR1C9, and RoDH2 activities with IC values of 100, 0.891 ± 0.065, and >100 μM, respectively. Apigenin competitively inhibited rat AKR1C9 when its substrate 5α-dihydrotestosterone was used and uncompetitively inhibited the enzyme when cofactor NADPH was used. In conclusion, apigenin is a potent inhibitor of rat AKR1C9, thereby controlling the rate of neurosteroid biosynthesis.
芹菜素是一种常见的黄酮类化合物，具有广泛的药理活性。芹菜素抑制一些甾体生物合成酶，表明它可能阻断神经甾体的合成。神经甾体在神经功能中发挥许多重要作用。本研究的目的是研究芹菜素对大鼠神经甾体生成酶 5α-还原酶 1（SRD5A1）、3α-羟甾脱氢酶（AKR1C9）和视黄醇脱氢酶 2（RoDH2）的影响。SRD5A1、AKR1C9 和 RoDH2 在 COS-1 细胞中表达，并使用放射性标记的底物和薄层层析分离结合放射测量法探索了芹菜素对这些酶的作用及其作用模式。芹菜素对 SRD5A1、AKR1C9 和 RoDH2 的抑制活性的 IC50 值分别为 100、0.891±0.065 和>100μM。当使用其底物 5α-二氢睾酮时，芹菜素竞争性抑制大鼠 AKR1C9，当使用辅因子 NADPH 时，非竞争性抑制该酶。总之，芹菜素是大鼠 AKR1C9 的有效抑制剂，从而控制神经甾体生物合成的速度。
