Details

Autor(en) / Beteiligte

• Wen, Fen
• Bian, DeZhi
• Wu, XuDong
• Liu, RuoBing
• Wang, ChaoNan
• Gan, JianHe

Titel

SU5, a new Auraptene analog with improved metabolic stability, ameliorates nonalcoholic fatty liver disease in methionine‐ and choline‐deficient diet‐fed db/db mice

Ist Teil von

• Chemical biology & drug design, 2022-03, Vol.99 (3), p.504-511

Ort / Verlag

England

Erscheinungsjahr

2022

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• Farnesoid X receptor (FXR) has been considered as a promising target for nonalcoholic steatohepatitis (NASH), while existing FXR agonists suffer from serious side effects. Thus, it is very necessary to identify novel FXR agonists with good safety. Auraptene (AUR) is a new FXR agonist with excellent safety and extensive pharmacological activities, while the lactone of AUR is vulnerable to esterolysis. In this study, the lactone of AUR was converted to metabolically stable amide moiety, and the obtained analog SU5 revealed comparable activity and better metabolic stability than that of AUR. In NASH model, SU5 showed stronger efficacy than AUR on fatty liver by upregulating gene expressions related to FXR in vivo. Moreover, SU5 improved lipid metabolism by downregulating the gene expressions of lipid synthesis, while upregulating the gene expressions of fatty acid β‐oxidation and triglyceride metabolism. Besides, the inflammation‐related genes were significantly decreased in SU5‐treated group. These positive results highlighted the pharmacological potential of SU5 for the treatment of NASH. SU5 revealed significantly better activity and metabolic stability than that of AUR. In NASH model, SU5 showed stronger efficacy than AUR on fatty liver by up‐regulating gene expressions related to FXR in vivo.