Taohong Siwu decoction ameliorates hepatic lipid accumulation in female mice with heart failure and preserved ejection fraction via AMPK/SREBP1 pathway

Dados Bibliográficos

ID15210488
AutoresWensheng Qi (0000-0001-9571-8821, Jilin University), Chang Liu (0000-0002-1198-6990, Jilin University), Dengke Li (0000-0002-4796-6764, Jilin University), Huihai Yang (0000-0002-9986-7362, Hong Kong Polytechnic University), Yue Li (0009-0004-9365-9070, Jilin University), Miao Zhang (0009-0008-4320-6232, Chinese University of Hong Kong), Dengwen Zhang (0000-0002-8673-7614, Guangdong Academy of Medical Sciences), Martin Ho Yin Yeung (0000-0001-8063-2929, Hong Kong Polytechnic University), Jie Chen (0000-0002-9254-4413, Shaoguan University), Jingjing Li (0009-0006-0033-1522, Hong Kong Polytechnic University), George Pak-Heng Leung (University of Hong Kong), Erfei Song (0000-0002-2492-5820, Guangzhou University of Chinese Medicine), Lei Pang (0000-0001-8529-4068, Jilin University), Haichun Ma (Jilin University, autor correspondente), Yin Cai (0000-0001-6781-7857, Hong Kong Polytechnic University, autor correspondente)
Ano2026
Volume366
Páginas121642-121642
Data de publicação2026-04-06
Peer ReviewedSim
Open AccessSim
TipoARTICLE
PeriódicoJournal of Ethnopharmacology (JOURNAL)
Identificadores do periódicoISSN: 0378-8741 • E-ISSN: 1872-7573
EditoraElsevier BV (PUBLISHER)
DOI10.1016/j.jep.2026.121642
PMID41951193
OpenAlexW7150816712
IdiomaEN
Referências citadas51

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine (TCM) theory, both heart failure with preserved ejection fraction (HFpEF) and metabolic dysfunction-associated fatty liver disease (MAFLD) are commonly associated with the syndrome of "qi stagnation and blood stasis," which manifests as cardiac dysfunction and hepatic metabolic disturbance, respectively. Taohong Siwu decoction (THSWD), a classic TCM formula documented in Yi Zong Jin Jian for promoting blood circulation and resolving stasis, is therefore a rational candidate to address this shared pathological basis. While THSWD's separate benefits for heart and liver have been reported, its potential to treat the interconnected pathology of HFpEF-associated MAFLD remains unexplored. AIM OF THE STUDY: This study aimed to investigate THSWD's therapeutic potential against HFpEF-associated MAFLD and its molecular mechanisms. MATERIALS AND METHODS: A two-hit HFpEF model was established in female mice. Hepatic lipid accumulation was evaluated by measuring triglyceride content, along with Oil Red O and H&E staining. THSWD constituents were identified by UPLC-Q-ToF/MS, and molecular targets were predicted through network pharmacology integrated with RNA-seq of liver tissues, then validated by qPCR and Western blotting. An in vitro steatotic HepG2 model further evaluated the effects of THSWD on lipid accumulation. RESULTS: THSWD significantly reduced hepatic lipid accumulation in HFpEF mice. UPLC-Q-ToF/MS identified 51 compounds in THSWD. Network pharmacology suggested these compounds target multiple lipid metabolism genes, particularly via the AMPK pathway. RNA-seq confirmed downregulation of key lipogenic SREBP1-regulated lipogenic genes (Acaca, Fasn, Scd1), validated by qPCR and Western blotting. In steatotic HepG2 cells, THSWD reduced lipid accumulation via AMPK/SREBP1 signaling, as this effect was abolished by either AMPK selective inhibitor or AMPKα1/α2 siRNA knockdown. Furthermore, when SREBP1 knockdown was combined with THSWD treatment, no additive effect on lipid reduction was observed compared to THSWD alone, indicating that SREBP1 mediates the lipid-lowering action of THSWD as a key downstream effector. CONCLUSION: This study provides the first evidence that THSWD alleviates HFpEF-associated MAFLD by suppressing lipid biosynthesis through AMPK/SREBP1 signaling, highlighting its potential as a therapeutic strategy for hepatic steatosis in HFpEF.

Decoction · Heart failure · Heart failure with preserved ejection fraction · Lipid accumulation · Lipid metabolism · Ratón · Cholesterol and Lipid Metabolism · Liver Disease Diagnosis and Treatment · Metabolism, Diabetes, and Cancer