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Chemistry & Biodiversity

Chemistry & Biodiversity

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Forsythoside B and Its Derivatives as Novel ASGR1 Inhibitors for Enhanced Cholesterol Efflux

Published:6 August 2025 DOI: 10.1002/cbdv.202501119 PMID: 40768748
Manru Ma, Rongfeng Liu, Yan Liu, Pengfei Xu, Yu Guo, Zhuoqian He, Zhongyin Zhang, KeWei Wang, Limei Wang

Abstract

The asialoglycoprotein receptor 1 (ASGR1), a hepatocyte-specific endocytic receptor, has recently emerged as a pivotal therapeutic target for metabolic diseases due to its critical role in regulating cholesterol efflux. Forsythoside B (FB), a naturally occurring phenylethanoid glycoside, has demonstrated lipid-modulating properties in previous studies. However, how it interacts with ASGR1-mediated cholesterol regulation remains unexplored. In this study, we systematically evaluated FB and its derivatives as novel ASGR1 inhibitors, focusing on their ability to promote cholesterol efflux in Huh-7 cells. Among the tested compounds, FB and its seven derivatives significantly enhanced cholesterol efflux in a concentration-dependent manner without affecting cell viability. Mechanistic studies revealed that these compounds exert their effects by inhibiting ASGR1. The findings of this study provide promising candidate molecules and establish a theoretical foundation for potential development of ASGR1-targeted cholesterol-lowering therapeutics.

Substances (16)

Materials
Procduct Name CAS Molecular Formula Supplier Price
DIGITONIN 11024-24-1 C56H92O29 375 suppliers $32.00-$3000.00
DIGITONIN 11024-24-1 C56H92O29 375 suppliers $32.00-$3000.00
DIGITONIN 11024-24-1 C56H92O29 375 suppliers $32.00-$3000.00
DIGITONIN 11024-24-1 C56H92O29 375 suppliers $32.00-$3000.00
6-[4-(2-PIPERIDIN-1-YLETHOXY)PHENYL]-3-PYRIDIN-4-YLPYRAZOLO[1,5-A]PYRIMIDINE 866405-64-3 C24H25N5O 269 suppliers $8.00-$2492.00
6-[4-(2-PIPERIDIN-1-YLETHOXY)PHENYL]-3-PYRIDIN-4-YLPYRAZOLO[1,5-A]PYRIMIDINE 866405-64-3 C24H25N5O 269 suppliers $8.00-$2492.00
6-[4-(2-PIPERIDIN-1-YLETHOXY)PHENYL]-3-PYRIDIN-4-YLPYRAZOLO[1,5-A]PYRIMIDINE 866405-64-3 C24H25N5O 269 suppliers $8.00-$2492.00
6-[4-(2-PIPERIDIN-1-YLETHOXY)PHENYL]-3-PYRIDIN-4-YLPYRAZOLO[1,5-A]PYRIMIDINE 866405-64-3 C24H25N5O 269 suppliers $8.00-$2492.00
GSK 2033 1221277-90-2 C29H28F3NO5S2 75 suppliers $32.00-$2246.00
GSK 2033 1221277-90-2 C29H28F3NO5S2 75 suppliers $32.00-$2246.00

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