Buyang huanwu decoction (BYHWD) attenuates sepsis-induced myocardial injury by suppressing aberrant iron accumulation in preclinical mouse models

作者：Lingling Xiao, Jun Lu, Meng Zhao, Ming Lei, Tao Zhang, Kai Zhang · 发表于：Phytomedicine · 年份：2025 · DOI：10.1016/j.phymed.2025.156689 · 被引用次数：8 · 研究领域：Plant-based Medicinal Research、Sepsis Diagnosis and Treatment、Cardiac Fibrosis and Remodeling

BACKGROUND: Sepsis-induced myocardial injury (SIMI), in particular, myocardial fibrosis, is frequently detected in septic patients and regarded as a key factor associated with sepsis-related mortality. PURPOSE: We sought to investigate whether the traditional Chinese medicine (TCM) prescription Buyang Huanwu Decoction (BYHWD) can alleviate early onset SIMI and improve the survival of septic mice. STUDY DESIGN: The lipopolysaccharide (LPS) and cecal ligation and puncture (CLP)-induced SIMI preclinical models were utilized to assess the therapeutic effect of BYHWD at low (1 mg/kg), median (5 mg/kg), and high (15 mg/kg) doses. METHODS: Multiple staining assays were employed for histopathological inspection, iron detection, and fibrotic status determination. In silico Network pharmacological and bioinformatics analyses were exploited to dissect molecular mechanism followed by in vitro and in vivo experimental validations using the immunostaining, immunoblotting, flow cytometry, RT-qPCR, and Ultra high performance liquid chromatography (UHPLC) assays. RESULTS: BYHWD attenuates SIMI and improves the survival of septic mice in a dose-dependent fashion. Mechanistically, sepsis-induced iron accumulation contributes to early onset SIMI. The aberrant iron overload in cardiac tissues is caused by elevated Heme Oxygenase-1 (Hmox1), which catalyzes Heme degradation and generates Biliverdin, Carbonic oxide (CO), and labile iron, thereby leading to iron accumulation. BYHWD-treated septic mic...