NATURAL PRODUCT RESEARCH AND DEVELOPMENT ›› 2024, Vol. 36 ›› Issue (3): 520-527. doi: 10.16333/j.1001-6880.2024.3.015

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Study on the mechanism of Astragali Radix extract in treating hypoxic-ischemic encephalopathy based on network pharmacology,molecular docking and experimental validation 

SONG Li-ya*,LI Li-hua,BI Si-tong   

  1. Department of Pediatrics,Luhe Hospital,Capital Medical University,Beijing 101149,China
  • Online:2024-03-20 Published:2024-03-20

Abstract:

Network pharmacology and molecular docking techniques were used to explore the mechanism of Astragali Radix extract in the treatment of hypoxic-ischemic encephalopathy (HIE).ischemic encephalopathy (HIE) was studied and verified.The main active components and gene targets of Astragali Radix extract were obtained through TCMSP,UniProt,GeneCards and OMIN databases,and HIE related targets were obtained through GeneCards database.The "active ingredient-drug target" network of Astragali Radix extract was constructed using Cytoscape software.PDB and TCMSP databases were used to obtain the molecular structure,and SYBYL-X2.1 software was used to simulate the molecular docking.The rat model was established and the expression of key proteins was detected by Western blot.According to the TCMSP database,a total of 70 active components and 350 related targets of Astragali Radix extract were obtained.After removing repeated targets and gene annotation,120 targets of active components of Astragali Radix extract were obtained.By mapping 120 targets of Astragali Radix extract with the first 242 targets of HIE (correlation score >5),18 potential targets of Astragali Radix extract for HIE were selected.4-Hydroxycinnamic acid,cis-ferulic acid,astrapterocarpan,hederagenin and kumatakenin were found to be the key active ingredients.Eighteen potential targets were input into STRING for protein interaction analysis,and a total of three core targets (degree>30) were found,which were respectively inducible nitric oxide synthase 2(NOS2),prostaglandin-endoperoxide synthase 2 (PTGS2),superoxide dismutase 1 (SOD1).Animal experiments showed that Astragali Radix extract could reduce the expression of NOS2,PTGS2,MAPK4 and CASP8 proteins in the hippocampus of rat models.Through network pharmacological analysis and experimental verification,it is concluded that Astragali Radix extract can inhibit neuronal apoptosis and protect nerve cells through multi-target and multi-pathway.

Key words: Astragali Radix extract, ischemic hypoxic encephalopathy, molecular docking, network pharmacology

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