Magnolol inhibits appetite and causes visceral fat loss through Growth/differentiation factor-15(GDF-15)by activating transcription factor 4-CCAAT enhancer binding proteinγ-mediated endoplasmic reticulum stress responses  

作　　者：Keru Cheng Yanyun Zhou Yilong Hao Shengyun Wu Nanping Wang Peng Zhang Yinfang Wang 

机构地区：[1]School of Basic Medicine,Anhui Medical University,Hefei 230032,China [2]Central Laboratory,Putuo Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200062,China [3]Health Science Center,East China Normal University,Shanghai 200241,China

出　　处：《Chinese Journal of Natural Medicines》2025年第3期334-345,共12页中国天然药物(英文版)

基　　金：supported by the National Natural Science Foundation of China(Nos.82171552 and 82170479);the Natural Science Foundation of Shanghai Ctiy(No.21ZR1457500);the Science and Technology Bureau of Shanghai Putuo District(No.ptkwws202102).

摘　　要：Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant,anticoagulant,and anti-diabetic effects.Growth/differentiation factor-15(GDF-15),a member of the transforming growth factorβsuperfamily,is considered a potential therapeutic target for metabolic disorders.This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism.The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo,and determined the involvement of endoplasmic reticulum(ER)stress signaling in this process.Luciferase reporter assays,chromatin immunoprecipitation,and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4(ATF4),CCAAT enhancer binding proteinγ(CEBPG),and CCCTC-binding factor(CTCF).The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene,as well as the influence of single nucleotide polymorphisms(SNPs)on magnolol and ATF4-induced transcription activity.Results demonstrated that magnolol triggers GDF-15 production in endothelial cells(ECs),hepatoma cell line G2(HepG2)and hepatoma cell line 3B(Hep3B)cell lines,and primary mouse hepatocytes.The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene.SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15.In high-fat diet ApoE^(-/-)mice,administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15.These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity,indicating its potential as a drug for the treatment of metabolic disorders.

关 键 词：MAGNOLOL Growth/differentiation factor-15 Activating transcription factor 4 CCAAT enhancer binding proteinγ ENHANCER Metabolic disorder 

分 类 号：R54[医药卫生—心血管疾病]