文献类型：期刊文献

英文题名：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

作者：Ren, Chunzhen[1,2,3];Wang, Lirong[1,2,3];Li, Xiaojing[1,2,3];Tang, Yan[1,2,3];Zhi, Xiaodong[1,2,3,4];Zhuang, Mengjie[5];Chen, Qilin[1,2,3];Gao, Xiang[1,2,3,4];Lv, Xinfang[1,2,3,4];Wang, Chunling[1,2,3];Wu, Xue[1,2,3];Liu, Kai[1,2];Zhao, Xinke[1,2,3,4];Li, Yingdong[1,2,3]

第一作者：Ren, Chunzhen;任春贞

通信作者：Zhao, XK[1];Li, YD[1];Zhao, XK[2]

机构：[1]Gansu Univ Chinese Med, Sch Tradit Chinese & Western Med, Lanzhou 730000, Gansu, Peoples R China;[2]Gansu Prov Key Lab Chinese Med Prevent & Treatment, Lanzhou 730000, Peoples R China;[3]Natl Adm Tradit Chinese Med, Natl Hlth Commiss, Key Specialized Cardiovasc Lab, Key Clin Specialty, Lanzhou 730000, Peoples R China;[4]Gansu Univ Chinese Med, Affiliated Hosp, Lanzhou 730000, Peoples R China;[5]Xinjiang Med Univ, Sch Basic Med Sci, Urumqi 830000, 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, Sch Tradit Chinese & Western Med, Lanzhou 730000, Gansu, Peoples R China;[2]corresponding author), Gansu Univ Chinese Med, Affiliated Hosp, Lanzhou 730000, Peoples R China.|[10735b845793de6ae2b30]甘肃中医药大学第二附属医院;[10735]甘肃中医药大学;

年份：2024

卷号：199

外文期刊名：EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001248396600001)】；

基金：This work was supported by the 2021 Gansu Jiaoyu Jiebang Guashuai Project (No. 2021 jyjbgs-03) , Gansu Province Traditional Chinese Medicine Prevention and Treatment of Major Diseases Special Project (No. GZKZD-2018-02), Gansu Province Major Science and Technology Special Project (No.20ZD7FA002), 2022 Gansu Province Longyuan Youth Innovation and Entrepreneurship Talent Project, 2022 Gansu Province natural sciences fund (22JR11RA128) and National Natural Science Foundation of China (NO. 82260869), National Administration of Traditional Chinese Medicine Youth Qihuang Scholars Support Project. 2021 '' Double First-Class"Scientific Research Key Project (No. GSSYLXM-05-ZXYJH-11), Gansu Provincial Youth Science and Technology Fund (23JRRA1217) and National Natural Science Foundation of China (NO. 82360926).

语种：英文

外文关键词：Radiation-induced myocardial fibrosis; Network pharmacology; Radix Angelica sinensis (Oliv.) Diels and Radix; Astragalus mongholicus bunge ultrafiltration extract; Inflammation; PI3K/AKT/mTOR pathway

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