Elucidating the mechanism of action of Radix Angelica sinensis (Oliv.) Diels and Radix Astragalus mongholicus Bunge ultrafiltration extract on radiation-induced myocardial fibrosis based on network pharmacology and experimental research

• DOI: 10.1016/j.ejps.2024.106794
• Publication Date: 2024-05-22T06:53:19Z
• Authors: Chunzhen Ren; Lirong Wang; Xiaojing Li; Yan Tang; Xiaodong Zhi; Mengjie Zhuang; Qilin Chen; Xiang Gao; Xinfang Lv; Chunling Wang; Xue Wu; Kai Liu; Xinke Zhao; Yingdong Li
• Keywords: Radix (gastropod); Astragalus; Angelica sinensis; Mechanism of Action

Myocardial fibrosis can induce cardiac dysfunction and remodeling. Great attention has been paid to Traditional Chinese Medicine (TCM) 's effectiveness in treating MF. Radix Angelica sinensis (Oliv.) Diels Astragalus mongholicus Bunge ultrafiltration extract (RAS-RA), which is a key TCM compound preparation, have high efficacy regulating inflammation. However, studies on its therapeutic effect radiation-induced myocardial (RIMF) are rare. In this study, RAS-RA had RIMF elucidated mechanism of action. First, we formulated the prediction network that described relation with according data obtained different databases. Then, conducted functional enrichment investigate functions pathways associated potential targets for RAS-RA. vivo experiments were also performed verify these pathways. Second, small animal ultrasound examinations, H&E staining, Masson transmission electron microscopy, Enzyme-linked immunosorbent assay (ELISA), Western-blotting, Immunohistochemical method biochemical assays possible anti-RIMF pathway total, 440 detected those 21 effective components RAS-RA; meanwhile, 1,646 RIMF-related disease discovered. After that, PPI analysis was identify 20 based 215 overlap gene targets. As indicated by Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) results, inflammation PI3K/AKT/mTOR might important effects RIMF. Molecular docking revealed binding (affinity < −6 kcal/mol). Based experimental verification greatly mitigated while recovering activity rats caused X-rays. According relevant protein expression profiles, anti-fibrosis Experimental showed improved function, decreased pathological damage collagen fiber deposition tissues, mitochondrial structure heart rats. downregulated TNF-α, IL-6, IL-1β levels. Additionally, liver kidney injury rat enhanced functions, protected kidneys. increased PI3K, AKT mTOR levels within tissues α-SMA, Collagen I, III. The findings study suggested suppressing inflammatory response inhibiting pathway. Thus, agent used alleviate