The Molecular Mechanism of FABP4 Inhibition Effects of GAS and 4-HBA in Blume Was Discussed Based on NMR and Molecular Docking

Overview

Journal J Anal Methods Chem

Publisher Wiley

Specialty Chemistry

Date 2024 May 16

PMID 38751858

Authors

Yuyu Yang

Shihan Liu

Wenfang Jin

Zengyi Qu

Baolei Fan

Affiliations

Soon will be listed here.

Abstract

To isolate gastrodin (GAS), 4-hydroxybenzyl alcohol (4-HBA), and phenolic compounds from Chinese medicine Blume, and to explore the binding mode of fatty acid binding protein 4 (FABP4/aP2) that is closely related to macrophage inflammation, we study their anti-inflammatory targets. After the ultrasonic extraction of the main active components with 70% ethanol, three resins and three eluents were selected, and eight phenolic monomers with similar structures, such as gastrodin and 4-hydroxybenzyl alcohol, were isolated from by AB-8 macroporous resin and silica gel column chromatography and eluted with the CHCl-MeOH gradient. Their structures were identified by HPLC and nuclear magnetic resonance (NMR). The FABP4 protein was added to GAS and 4-HBA, and the NMR experiment was performed to observe ligand binding. Finally, according to the spectral information of STD-NMR and molecular docking technology, the interaction between ligands and protein was studied. The fluorescence competition experiment confirmed that both GAS and 4-HBA were in the binding cavity of FABP4. Moreover, 3-phenoxy-2-phenylbenzoic acid (PPA) is a possible inhibitor of FABP4, reducing macrophage-related inflammation and endoplasmic reticulum stress. This work provides a new basis for the anti-inflammatory mechanism of , paving the way for the research and development of FABP4 inhibitor drugs.

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