基于临床处方数据挖掘、网络药理学及分子对接分析中药治疗多发性硬化的用药规律及作用机制OA

Objective This study aimed to mine prescription patterns and identify the core herbal combination based on real-world clinical prescription data from patients with multiple sclerosis(MS),and to explore its potential mechanisms using network pharmacology and molecular docking,thereby providing clinical evidence and theoretical support for traditional Chinese medicine(TCM)treatment of MS.Methods(1)Prescription data from patients with MS who visited the department of traditional Chinese medicine,Beijing Tiantan Hospital,Capital Medical University,between January 1,2014 and January 1,2025 were retrospectively collected.After standardization of the prescriptions,frequency analysis,association rule analysis,and cluster analysis were performed to identify core herbal combinations.(2)Using the screened core herbal combination,Rehmanniae Radix-Rehmanniae Radix Praeparata-Corni Fructus-Moutan Cortex,as the research object,active compounds and potential targets were obtained from the TCMSP and HERB databases,while MS-related disease targets were collected from the GeneCards,DisGeNET,OMIM,and BrainBase databases.Cytoscape was used to construct the herb-compound-target interaction network.Gene Ontology(GO)functional analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were then performed for the potential targets.Molecular docking using AutoDock Vina was further conducted to validate the binding of key active compounds to core targets.Results(1)A total of 446 prescriptions involving 161 herbs were analyzed.Eighteen herbs with a frequency≥100 were identified,with the top five being Semen Persicae(72.20%),Radix Achyranthis Bidentatae(61.66%),Radix Rehmanniae Praeparata(50.67%),Flos Carthami(48.65%),and Radix Rehmanniae(44.62%).Association rule analysis identified several strongly correlated herb pairs,including Carthami Flos-Persicae Semen(confidence=0.99)and Rehmanniae Radix Praeparata-Rehmanniae Radix(confidence=0.81).Cluster analysis grouped the core herbs into seven categories,forming a treatment framework mainly characterized by C1(kidney-tonifying and blood-activating),C3(liver-calming and wind-extinguishing),and C5(qi-tonifying,blood-activating,and collateral-unblocking)clusters.Based on frequency analysis,association rule analysis,and cluster analysis,the core herbal combination Rehmanniae Radix-Rehmanniae Radix Praeparata-Corni Fructus-Moutan Cortex was identified.(2)Network pharmacology analysis identified 565 intersecting targets of this core herbal combination against MS.Key targets included TP53,Akt1,STAT3,and JUN,mainly involving the PI3K-Akt signaling pathway,MAPK signaling pathway,and neuroactive ligand-receptor interaction pathway.Molecular docking showed a certain binding tendency between the key active compounds and core targets,among which quercetin exhibited relatively strong binding to JUN,Akt1,and STAT3,while rehmapicroside showed relatively strong binding to JUN.Conclusion Based on real-world clinical prescription data mining,this study identified Rehmanniae Radix-Rehmanniae Radix Praeparata-Corni Fructus-Moutan Cortex as the core herbal combination for MS,reflecting the compatibility characteristics of simultaneously emphasizing kidney-tonifying and essence-replenishing with blood-activating and collateral-unblocking strategies in clinical treatment.This herbal combination may act through key compounds such as quercetin and rehmapicroside on core targets including TP53,Akt1,STAT3,and JUN,and exert integrated therapeutic effects through pathways such as PI3K-Akt,MAPK,and neuroactive ligand-receptor interaction at multiple levels,including abnormal immune activation,amplification of inflammatory cascades,and imbalance between neural injury and repair.These findings provide a theoretical basis for the clinical prescription and mechanistic research of traditional Chinese medicine in the treatment of multiple sclerosis.