文献类型：期刊文献

英文题名：Elucidating the mechanism of action of astragalus polysaccharide on ionizing radiation-induced myocardial damage based on network pharmacology and experimental research

作者：Jiang B.; Wang Y.; Zhi X.; Liu A.; Wang L.; Wang X.; Wang Z.; Duan Y.; Li Y.; Zhang Z.

第一作者：Jiang B.

机构：[1]Department of Integrated Chinese and Western Medicine, Gansu University of Chinese Medicine, Gansu, Lanzhou, 730000, China;[2]Clinical College of Traditional Chinese Medicine, Gansu University of Chinese Medicine, Gansu, Lanzhou, 730000, China;[3]Affiliated Hospital of Gansu University of Chinese Medicine, Gansu, Lanzhou, 730000, China;[4]Gansu Province Key Laboratory of Chinese Medicine for the Prevention and Treatment of Chronic Diseases, Gansu, Lanzhou, 730000, China;[5]Department of First Clinical Medicine, Lanzhou University, Gansu, Lanzhou, 730000, China;[6]Department of Ultrasound, Gansu Provincial Cancer Hospital, Gansu, Lanzhou, 730050, China;[7]Center for Heart, Lanzhou University of the First Hospital, Gansu, Lanzhou, 730030, China

第一机构：甘肃中医药大学

年份：2025

卷号：145

外文期刊名：International Immunopharmacology

收录：Scopus(收录号：2-s2.0-85211153140)

语种：英文

外文关键词：Astragalus polysaccharide; Autophagic flux; Ionizing radiation; Mitochondrial apoptosis; Myocardial injury; PI3K/Akt/mTOR signaling pathway

摘要：Due to the unavoidable impact of ionizing radiation on the heart located near the mediastinum, varying degrees of myocardial damage may occur. As a result, the clinical application of radiotherapy in cancer treatment is significantly limited. However, the molecular mechanisms underlying radiation-induced heart disease (RIHD) are not yet fully understood, and there is a lack of disease-specific treatment strategies. Astragalus polysaccharide (APS), is an active compound abundant in the traditional Chinese herb Astragalus membranaceus (Fisch.) Bunge (AS), has been shown to have cardioprotective effects against various cardiovascular diseases. Thus, this study aims to investigate the potential cardioprotective effect of APS on RIHD and its underlying molecular mechanisms. The network pharmacology results indicated that 9 core genes were identified from the biological network of the effective components of AS acting on RIHD. The results of GO enrichment analysis showed that these hub genes were mainly involved in biological processes such as cell apoptosis, cell proliferation, inflammatory response, and response to external stimuli. The results of KEGG enrichment analysis showed that these hub genes mainly regulated the occurrence of RIHD through pathways such as the EGFR signaling pathway, PI3K/Akt signaling pathway, IL-17 signaling pathway, and so on. In molecular docking analysis, we found that AKT1 and mTOR had good and stable binding abilities with the three types of glucosides rich in AS. The results of in vitro and in vivo experiments all showed that APS could not only improve cardiac dysfunction, myocardial injury, inflammatory response, and myocardial fibrosis in RIHD rats, but also alleviated apoptosis and atrophy of H9C2 cells under ionizing radiation stimulation. In addition, we also found that APS improved the accumulation of autophagic flux induced by ionizing radiation, which could be confirmed by the reversal of Beclin1, p62, LC3B proteins and accelerated degradation of accumulated autophagic vesicles. Rapamycin (Rap) was a classic autophagy flux inducer that could attenuate the improvement effect of APS on H9C2 cell apoptosis under ionizing radiation stimulation. Finally, we found that APS could reverse the inhibition of PI3K/Akt/mTOR signaling pathway activity by ionizing radiation in vitro, thereby improving ionizing radiation-induced autophagy flux accumulation, cardiomyocyte apoptosis, and atrophy. All in all, this study provides important evidence for understanding the molecular mechanisms of the cross-talk between autophagy and apoptosis, and provides new directions and insights for APS combined with autophagy regulators as a therapeutic strategy for RIHD. ? 2024 Elsevier B.V.