文献类型：期刊文献

英文题名：Formononetin, an active component of RAS-RH, ameliorates radiation-induced mitochondrial fission dysfunction in endothelial cells via TCs-ECs crosstalk

作者：Liu, Ai[1];Lu, Weijie[1];Jiang, Hugang[1];Li, Linchan[1];Guo, Zeao[1];Liu, Jiakun[1];Lu, Guoci[1];Yuan, Jianfang[1];Zhao, Xinke[1,2];Li, Yingdong[1,2]

第一作者：Liu, Ai

通信作者：Li, YD[1]

机构：[1]Gansu Univ Chinese Med, Dept Tradit Chinese & Western Med, Lanzhou 730000, Gansu, Peoples R China;[2]Gansu Univ Chinese Med, Affiliated Hosp, Cardiovasc Clin Med Ctr, Lanzhou 730000, Gansu, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Lanzhou 730000, Peoples R China.|[10735ed249c6606940a33]甘肃中医药大学中西医结合学院;[10735]甘肃中医药大学;

年份：2026

卷号：165

外文期刊名：MICROVASCULAR RESEARCH

收录：;Scopus(收录号：2-s2.0-105031662238);WOS:【SCI-EXPANDED(收录号:WOS:001710260700001)】；

基金：Funding This work was supported by grants from the National Natural Science Foundation of China (Nos. 82374279 and 82360926) and the Natural Science Foundation of Gansu Province (No. 23JRRA1217) . The funding agencies had no involvement in study design, data collection, analysis, decision to publish, or manuscript preparation.

语种：英文

外文关键词：RAS-RH; Formononetin; TCs-ECs crosstalk; miR-151a-5p; Mitochondrial fission

摘要：Objective: This study aimed to investigate the mechanisms by which the ultrafiltrate of Radix Angelicae Sinensis and Hedysari (RAS-RH) and its active component formononetin alleviate X-ray radiation-induced injury in rat cardiac microvascular endothelial cells (CMECs) through modulation of cardiac telocytes (TCs)-mediated paracrine signaling. Methods: An in vitro radiation-induced CMEC injury model was established. Mitochondrial function, proliferation, migration, angiogenesis, and apoptosis were assessed using transmission electron microscopy, flow cytometry, mitochondrial probes, 5-ethynyl-2 '-deoxyuridine staining, wound-healing and tube-formation assays, Western blotting, and immunofluorescence. Single-cell RNA sequencing, network pharmacology, molecular docking, and molecular dynamics simulations were used to identify formononetin as the key active component of RAS-RH and to predict its regulatory targets. Reverse transcription quantitative real-time polymerase chain reaction and in situ hybridization further validated the underlying mechanisms. Results: X-ray radiation decreased the mitochondrial membrane potential, increased reactive oxygen species levels, and upregulated the expression of mitochondrial fission-related proteins: mitochondrial fission 1 protein (Fis1), dynamin-related protein 1,and mitochondrial fission factor, thereby inducing mitochondrial dysfunction. These changes suppressed endothelial cells (ECs) proliferation, migration and tube formation and downregulated the expression of endothelial growth factors, such as vascular endothelial growth factor, basic fibroblast growth factor, and angiopoietin-2. In contrast, formononetin, as the active component of RAS-RH upregulated androgen receptor (AR) transcription in TCs and enhanced the expression and paracrine release of TCs-derived miR-151a-5p, which subsequently downregulated Fis1 expression in ECs and inhibited Fis1-mediated excessive mitochondrial fission. Through these mechanisms, formononetin attenuated X-ray-radiation-induced endothelial dysfunction. Conclusion: Formononetin, the active component of RAS RH, mediates TCs-ECs crosstalk through the AR/miR-151a-5p/Fis1 axis, which represents the core mechanism for inhibiting excessive mitochondrial fission in ECs and alleviating EC injury.