Professor Lu Jianqi's Academic Experience for Treating Arrhythmias and the Molecular Mechanisms of Regulating Ferroptosis Based on Data Mining and Network Pharmacology

MAO Meiling; LU Jianqi; SHI Weiqi; CHEN Jiayong; LU Jie; HAN Jingbo; LIANG Yiqiang; LU Junshen

doi:10.12102/j.issn.1672-1349.2025.22.003

Abstract：Objective:To summarize Professor Lu Jianqi's academic experience for treating arrhythmia and to reveal the molecular mechanism of regulating ferroptosis based on data mining and network pharmacology techniques.Methods:From December 2018 to December 2022,the outpatient cases of Professor Lu Jianqi were selected.The PageRank algorithm was applied on the Fangwang platform.According to the clustering model of traditional Chinese medicine,core medicinal materials and medicinal materials,the usage frequency of traditional Chinese medicine and its four natures and five flavors was analyzed.The top 6 drugs with the highest frequency were selected as high-frequency traditional Chinese medicine.The active ingredients of high-frequency traditional Chinese medicine were retrieved from the TCMSP database.The arrhythmia targets were screened by the GeneCards,OMIM,TTD,and PharmGkb databases.The potential common molecular targets of " high-frequency traditional Chinese medicine-arrhythmia-ferroptosis" were obtained through the Draw Venn Diagram website.The protein-protein interaction(PPI)network was constructed using the STRING platform.The core targets were screened by network topology calculation using Cytoscape 3.8.0 software.Gene ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed with R 4.2.3 to construct the "active ingredient-target" network.Results:A total of 1 083 prescriptions were included,with a cumulative use of 16 063 times of traditional Chinese medicine,involving 262 kinds of drugs.The high-frequency traditional Chinese medicines with frequency of more than 500 times were Glycyrrhiza uralensis,Cinnamomum cassia,Atractylodes macrocephala,Pinellia ternata,Codonopsis pilosula,and Poria cocos.After summary and deduplication from the TCMSP database,135 effective components were obtained,and 243 potential targets were identified after screening.There were 1 819 arrhythmia genes obtained from the four disease databases of GeneCards,OMIM,TTD,and PharmGkb.A total of 561 ferroptosis genes were obtained from the FerrDB database,and the intersections were taken to obtain 26 common intersection targets of "high-frequency traditional Chinese medicine-arrhythmia-ferroptosis".The 26 intersection targets were imported into the STRING database and Cytoscape 3.8.0 software to obtain the PPI network diagram.There were 12 core proteins obtained based on the degree value≥20,including interleukin-1β(IL1B),interleukin-6(IL6),signal transducer and activator of transcription 3(STAT3),tumor protein p53(TP53),prostaglandin-endoperoxide synthase 2(PTGS2),hypoxia-inducible factor 1α subunit(HIF1A),peroxisome proliferator-activated receptor γ(PPARG),mitogen-activated protein kinase 3(MAPK3),epidermal growth factor receptor(EGFR),caveolin-1(CAV1),interferon γ(IFNG),nuclear factor E2-related factor 2(NFE2L2).The GO functional enrichment analysis and KEGG pathway enrichment analysis results of 26 core targets were obtained through the DAVID database and R language software(R 4.2.3).GO enrichment analysis included 120 molecular functions,mainly enriched in RNA polymerase Ⅱ-specific DNA-binding transcription factor binding,DNA-binding transcription factor binding,phosphatase binding.There were 1 820 biological processes,mainly enriched in oxidative stress responses,cellular responses to chemical stress,wound healing,responses to hypoxia.There were 26 cell components,mainly enriched in membrane rafts,membrane microdomains,focal adhesions,cell-substrate junctions.A total of 151 KEGG pathway enrichment analysis were obtained,involving the hypoxia-inducible factor-1(HIF-1)signaling pathway,the human cytomegalovirus infection pathway,the proteoglycan pathway in cancer,lipids and atherosclerosis,T helper 17 cell(Th17)cell differentiation,the advanced glycation end products(AGE)-advanced glycation end products receptor(RAGE)signaling pathway,and interleukin-17(IL-17)signaling pathway.Conclusion:Professor Lu Jianqi treated arrhythmia with traditional Chinese medicine,and the main therapeutic principle of "supplement and boost the Qi and blood,Yin and Yang,rectify Qi,invigorate blood,dissolve phlegm and unblock the collaterals",while he payed attention to "protecting the heart spirit".The core Chinese herbs included licorice,cinnamon twigs,Atractylodes macrocephala,Pinellia ternata,Codonopsis pilosula and poria cocos.It mainly acted on key ferroptosis targets such as STAT3,TP53,PTGS2,HIF1A,PPARG,MAPK3,EGFR,and CAV1,involving pathways such as the HIF-1 signaling pathway,lipids and atherosclerosis,Th17 cell differentiation,AGE-RAGE,and IL-17 signaling pathways.