The Mechanism of Rhodiola Crenulata for Treating Plateau Hypoxic Brain Injury and Experimental Verification
LIU Fangzhou
LI Yuanbai
YANG Yang
MA Siqing
Abstract:Objective:To explore the mechanism of Rhodiola Crenulata for treating plateau hypoxic brain injury based on reverse molecular docking and experimental verification.Methods:The chemical components of Rhodiola Crenulata were collected by searching the comprehensive Chinese medicine database(ETCM),the database of the association between Chinese medicine and disease symptoms(SymMap),and through supplementary literature collection.The active ingredients with absorption,distribution,metabolism,and excretion(ADME)prediction results were screened using the drug screening platform(FAFDrugs4).The potential targets of active ingredients were predicted by reverse molecular docking method.The targets related to plateau hypoxic brain injury were obtained from the human gene database(GeneCards).The common targets of medicinal materials and diseases were obtained.The"traditional Chinese medicine-component-target-disease"regulatory network and the common target protein-protein interaction(PPI)network were constructed.The core targets were obtained through network topology analysis.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analyses were conducted using the OmicShare software,and in vivo pharmacodynamic experiments were carried out for verification.The regulatory effect of Rhodiola Crenulata on the expression of core target messenger ribonucleic acid(mRNA)in the hippocampal tissue of rats with plateau hypoxic brain injury was detected by the real-time fluorescent quantitative polymerase chain reaction(RT-PCR).Western blot was used to detect the regulatory effect of Rhodiola Crenulata on the protein expression of serine/threonine protein kinase 1(AKT1)and signal transducer and activator of transcription 3(STAT3)in brain tissue of rats with low-pressure oxygen combined with lipopolysaccharide(LPS)-induced brain injury,further confirming the results of network pharmacology analysis.Results:A total of 76 active components and 285 targets were screened from Rhodiola Crenulata.One hundred and forty-eight disease targets related to plateau hypoxic brain injury were obtained,with 23 common targets.The core targets included AKT1,heat shock protein 90α1(HSP90AA1),albumin(ALB),estrogen receptor 1(ESR1),and STAT3.GO enrichment analysis yielded 1 607 entries,and KEGG enrichment analysis identified 71 pathways.Rhodiola Crenulata could down-regulate the mRNA expression levels of the core targets serine/AKT1 and STAT3.Rhodiola Crenulata could inhibit the phosphorylation of serine/AKT1 protein,and all doses could significantly inhibit the expression of STAT3 protein(P<0.01).Conclusion:Rhodiola Crenulata could treat plateau hypoxic brain injury through multi-target and multi-pathway.
Keywords:plateau hypoxic brain injuryRhodiola Crenulatareverse molecular dockingmechanism
Publication Date:2026-03-25
Online Publishing Date:2026-04-07(First online date of this platform, not the publication date of the document)
Pages:8( 885-892 )