Resveratrol analogues and metabolites selectively inhibit human and rat 11ß-hydroxysteroid dehydrogenase 1 as the therapeutic drugs: structure-activity relationship and molecular dynamics analysis.
SAR QSAR Environ Res
; 35(7): 641-663, 2024 Jul.
Article
in En
| MEDLINE
| ID: mdl-39139138
ABSTRACT
Resveratrol is converted to various metabolites by gut microbiota. Human and rat liver 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) are critical for glucocorticoid activation, while 11ß-HSD2 in the kidney does the opposite reaction. It is still uncertain whether resveratrol and its analogues selectively inhibit 11ß-HSD1. In this study, the inhibitory strength, mode of action, structure-activity relationship (SAR), and docking analysis of resveratrol analogues on human, rat, and mouse 11ß-HSD1 and 11ß-HSD2 were performed. The inhibitory strength of these chemicals on human 11ß-HSD1 was dihydropinosylvin (6.91 µM) > lunularin (45.44 µM) > pinostilbene (46.82 µM) > resveratrol (171.1 µM) > pinosylvin (193.8 µM) > others. The inhibitory strength of inhibiting rat 11ß-HSD1 was pinostilbene (9.67 µM) > lunularin (17.39 µM) > dihydropinosylvin (19.83 µM) > dihydroresveratrol (23.07 µM) > dihydroxystilbene (27.84 µM) > others and dihydropinosylvin (85.09 µM) and pinostilbene (>100 µM) inhibited mouse 11ß-HSD1. All chemicals did not inhibit human, rat, and mouse 11ß-HSD2. It was found that dihydropinosylvin, lunularin, and pinostilbene were competitive inhibitors of human 11ß-HSD1 and that pinostilbene, lunularin, dihydropinosylvin, dihydropinosylvin and dihydroxystilbene were mixed inhibitors of rat 11ß-HSD1. Docking analysis showed that they bind to the steroid-binding site of human and rat 11ß-HSD1. In conclusion, resveratrol and its analogues can selectively inhibit human and rat 11ß-HSD1, and mouse 11ß-HSD1 is insensitive to the inhibition of resveratrol analogues.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Stilbenes
/
11-beta-Hydroxysteroid Dehydrogenase Type 1
/
Molecular Docking Simulation
/
Resveratrol
Limits:
Animals
/
Humans
Language:
En
Journal:
SAR QSAR Environ Res
Journal subject:
SAUDE AMBIENTAL
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
United kingdom