姜黄素类似物对人和大鼠性腺 3β-羟甾脱氢酶具有很强的抑制作用，可作为潜在的治疗药物：构效关系和计算机对接研究。

Curcumin analogues exert potent inhibition on human and rat gonadal 3β-hydroxysteroid dehydrogenases as potential therapeutic agents: structure-activity relationship and in silico docking.

机构信息

Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Reproductive Medicine Center, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

出版信息

J Enzyme Inhib Med Chem. 2023 Dec;38(1):2205052. doi: 10.1080/14756366.2023.2205052.

Curcuminoids are functional food additives, and the effect on gonadal hormone biosynthesis remains unclear. Gonads contain 3β-hydroxysteroid dehydrogenase isoforms, 3β-HSD2 (humans) and r3β-HSD1 (rats), which catalyse pregnenolone into progesterone. The potency and mechanisms of curcuminoids to inhibit 3β-HSD activity were explored. The inhibitory potency was bisdemethoxycurcumin (IC, 1.68 µM) >demethoxycurcumin (3.27 µM) > curcumin (13.87 µM) > tetrahydrocurcumin (109.0 µM) > dihydrocurcumin and octahydrocurcumin on KGN cell 3β-HSD2, while that was bisdemethoxycurcumin (1.22 µM) >demethoxycurcumin (2.18 µM) > curcumin (4.12 µM) > tetrahydrocurcumin (102.61 µM) > dihydrocurcumin and octahydrocurcumin on testicular 3β-HSD1. All curcuminoids inhibited progesterone secretion by KGN cells under basal and forskolin-stimulated conditions at >10 µM. Docking analysis showed that curcuminoids bind steroid-active site with mixed or competitive mode. In conclusion, curcuminoids inhibit gonadal 3β-HSD activity and de-methoxylation of curcumin increases inhibitory potency and metabolism of curcumin by saturation of carbon chain losses inhibitory potency.

姜黄素类是功能性食品添加剂，但其对性腺激素生物合成的影响尚不清楚。性腺含有 3β-羟甾脱氢酶同工酶，即 3β-HSD2（人类）和 r3β-HSD1（大鼠），它们催化孕烯醇酮生成孕酮。本研究旨在探讨姜黄素类抑制 3β-HSD 活性的作用和机制。结果显示，双去甲氧基姜黄素（IC，1.68 μM）＞去甲氧基姜黄素（3.27 μM）＞姜黄素（13.87 μM）＞四氢姜黄素（109.0 μM）＞二氢姜黄素和八氢姜黄素对 KGN 细胞 3β-HSD2 的抑制作用最强，而双去甲氧基姜黄素（1.22 μM）＞去甲氧基姜黄素（2.18 μM）＞姜黄素（4.12 μM）＞四氢姜黄素（102.61 μM）＞二氢姜黄素和八氢姜黄素对睾丸 3β-HSD1 的抑制作用最强。所有姜黄素类在>10 μM 时均可抑制 KGN 细胞基础和 forskolin 刺激下的孕酮分泌。对接分析显示，姜黄素类以混合或竞争性模式结合甾体活性部位。综上所述，姜黄素类抑制性腺 3β-HSD 活性，姜黄素脱甲氧基增加其抑制作用，而碳链饱和则降低其抑制作用。