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

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

  • J Enzyme Inhib Med Chem. 2023 Dec;38(1):2205052. doi: 10.1080/14756366.2023.2205052.
Xinyi Qiao 1,  Lei Ye 1,  Jialin Lu 1,  Chengshuang Pan 1 2,  Qianjin Fei 2,  Yang Zhu 1 3,  Huitao Li 1 3,  Han Lin 1,  Ren-Shan Ge 1 3,  Yiyan Wang 1 3
Affiliations

Affiliations

  • 1 Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
  • 2 Reproductive Medicine Center, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • 3 Key Laboratory of Structural Malformations in Children of Zhejiang Province, Key Laboratory of Environment and Male Reproductive Medicine of Wenzhou, Wenzhou, China.
PMID: 37184069 DOI: 10.1080/14756366.2023.2205052
Abstract

Curcuminoids are functional food additives, and the effect on gonadal hormone biosynthesis remains unclear. Gonads contain 3β-hydroxysteroid dehydrogenase isoforms, h3β-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 (IC50, 1.68 µM) >demethoxycurcumin (3.27 µM) > curcumin (13.87 µM) > tetrahydrocurcumin (109.0 µM) > dihydrocurcumin and octahydrocurcumin on KGN cell h3β-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 r3β-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.

Keywords

Curcumin analogues; curcumin metabolite; docking analysis; gonad 3β-HSD; inhibition.

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