Exploring the mechanism of Radix Angelica sinensis and Astragalus mongholicus extract therapy for radiationinduced myocardial fibrosis based on network pharmacology and experimental validation
AIM:To explore the potential targets and mechanisms of Angelica sinensis and Astraga-lus membranaceus ultrafiltration(RAS-AM)in the treatment of radiation induced myocardial fibrosis(RIMF)through network pharmacology combined experimental validation.METHODS:Using the TC-MSP database TCM@TAIWAN The Taiwan Tradition-al Chinese Medicine Database and TCMID Tradition-al Chinese Medicine Database screen the compo-nents and targets of RAS-AM,and use the Swiss Target Prediction database for target prediction.Obtain RIMF disease targets from Gene Cards and OMIM databases,obtain intersection targets of dis-eases and drugs through Wayne's online tool,ob-tain protein interaction relationships(PPIs)through STRING database,and use Cytoscape 3.9.1 soft-ware to construct a visualized network topology di-agram of"drug component target disease".Con-duct GO and KEGG enrichment analysis on core tar-gets through the David database,and use the mi-crobiome platform for mapping.Experimental veri-fication:Sixty Wistar rats were randomly divided in-to a blank group,a model group,a positive drug group,a RAS-AM low-dose group,a RAS-AM medi-um dose group,and a RAS-AM high-dose group.A RIMF model was established using a 38Gy dose of radiation induction,and was administered orally for 4 weeks.The general condition of the rats was also observed.After blood and heart collection in rats,HE staining was used to observe the morpho-logical changes of myocardial tissue,and ELISA and Western blot methods were used to detect key tar-gets for network pharmacology prediction.RE-SULTS:Network pharmacology analysis revealed 34 active components and 705 targets of Angelica si-nensis and Astragalus membranaceus ultrafiltra-tion,with a total of 154 targets,with IL-6,VEGFA,MMP2,MMP9,and ACE as the top five core tar-gets;GO enrichment analysis screened a total of 153 entries,and KEGG enrichment had 25 path-ways.Experimental part:HE staining results showed that the degeneration and necrosis of myo-cardial cells improved in each medication group,the infiltration of inflammatory cells in the myocar-dial interstitium decreased,and the proliferation of fibrous connective tissue in the myocardial intersti-tium decreased.ELISA and Western blot results showed that compared with the normal group,the expression of IL-6,VEGFA,and MMP-9 in the mod-el group increased.Compared with the model groupthe expression of IL-6,VEGFA,and MMP-9 in each medication group decreased to varying de-grees,in a dose-dependent manner.CONCLUSION:RAS-AM may inhibit RIMF by downregulating core targets such as IL-6,VEGFA protein,MMP-9 pro-tein,and regulating inflammatory pathways,colla-gen degradation,and other processes.
Angelica sinensis and Astragalus membranaceus ultrafiltrationradiationinduced myocardial fibrosisnetwork pharmacologyIL-6VEGFAMMP-9
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