Objective To explore the characteristics, medication patterns, and the mechanisms of action of traditional Chinese medicines for treating angle-closure glaucoma. Methods Literature and prescriptions related to the treatment of angle-closure glaucoma with traditional Chinese medicine were retrieved from databases including CNKI, Wanfang, VIP, China Biology Medicine (CBM), and the Ancient and Modern Medical Case Cloud Platform. Through data mining and analysis, core prescriptions were identified. Subsequently, a network pharmacology approach was employed. Active ingredients with oral bioavailability (OB) ≥ 30% and drug-likeness (DL) ≥ 0.18 were screened using the TCMSP and BATMAN-TCM 2.0 databases. Targets were uniformly annotated via the UniProt database and intersected with disease targets obtained by integrating and deduplicating data from four major databases (GeneCards, TTD, OMIM, and CTD) to identify pharmacodynamic targets. A “core prescription-active ingredient-pharmacodynamic target” interaction network was constructed using Cytoscape 3.10.2. The pharmacodynamic targets were then imported into the Metascape platform (restricted to human species, with a threshold of P < 0.05) for gene ontology (GO) (biological process, molecular function, cellular component) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis, with the top 20 significant pathways and functions visualized. Additionally, a protein-protein interaction (PPI) network was constructed using the String database, and core targets were screened using the Cytoscape MCODE plugin (cut-off = 0.05) to elucidate the potential molecular mechanisms underlying the core prescriptions in treating angle-closure glaucoma. The binding energy between the active ingredient and the core target was investigated through molecular docking. Sodium dithionite was used to induce hypoxic injury in mouse retinal ganglion cells (RGCs) to establish an in vitro model. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was employed to detect the effects of these active components on mRNA expression of core target genes. ELISA was used to measure the impact of these active components on tumor necrosis factor-α (TNF-α) levels. Immunofluorescence staining was applied to evaluate the effects of these active components on phosphorylated protein kinase B (p-AKT) and nuclear factor-κB (NF-κB) protein expression. Results The top three most frequently used traditional Chinese medicines for angle-closure glaucoma were Fuling (Poria), Danggui (Angelicae Sinensis Radix), and Chaihu (Bupleuri Radix). The core syndromes were mainly liver qi stagnation and liver-kidney deficiency. A core prescription consisted of Mudanpi (Moutan Cortex)-Angelicae Sinensis Radix-Zhizi (Gardeniae Fructus)-Bupleuri Radix-Juhua (Chrysanthemi Flos)-Baizhu (Atractylodis Macrocephalae Rhizoma)-Gancao (Glycyrrhizae Radix et Rhizoma)-Baishao (Paeoniae Radix Alba)-Poria. Cluster analysis yielded three clusters: modified Chaihu Shugan San (柴胡疏肝散), modified Yijing Buyang Huanwu Decoction (益精补阳还五汤), modified Qiju Dihuang Pills (杞菊地黄丸). Network pharmacology analysis showed that the core prescription regulated key targets such as AKT1, TNF-α, NF-κB by modulating signalling pathways such as TNF, phosphatidylinositol-3-hydroxykinase (PI3K)-Akt, and MAPK (mitogen-activated protein kinase), thereby participating in biological processes such as inflammatory response, and oxidative stress, and thus intervening in the pathological process of glaucoma. Quercetin and luteolin were identified as the core components of the core prescription for the intervention of angle-closure glaucoma through molecular docking, and in vitro experiments were conducted for verification. The results showed that all luteolin dose groups (5, 10, 20 μmol/L) upregulated AKT1 mRNA expression (P < 0.01), while the medium and high dose groups downregulated NF-κB and TNF-α mRNA expression (P < 0.05), significantly increased p-AKT protein expression, and decreased NF-κB protein and TNF-α levels (P < 0.05). The medium and high dose groups of quercetin (40, 80 μmol/L) also significantly upregulated AKT1 mRNA expression and downregulated NF-κB and TNF-α mRNA expression (P < 0.05). All low (20 μmol/L), medium, and high dose groups of quercetin increased p-AKT protein expression and decreased NF-κB protein expression (P < 0.05), while the medium and high dose groups significantly reduced TNF-α expression (P < 0.05). Conclusion Data mining techniques were systematically employed to analyze ancient and modern literature and medical records concerning the treatment of angle-closure glaucoma. From multiple dimensions including medication frequency, nature-flavor-meridian tropism, efficacy categories, association rules, and core combinations, the “high-frequency-core-differential” three-dimensional characteristics were progressively analyzed to extract core prescriptions and reveal their compatibility patterns. Network pharmacology analysis further confirmed that the above high-frequency prescriptions synergistically regulate key biological processes such as oxidative stress, inflammatory response, and apoptosis through a “multi-component-multi-target-multi-pathway” mechanism, reflecting the holistic therapeutic advantages of traditional Chinese medicine compound formulas, thereby providing scientific evidence for clinical syndrome differentiation and medication, with certain guiding significance. In vitro experiments simultaneously validated that, in the hypoxic injury model, both luteolin and quercetin significantly upregulated AKT1 mRNA and p-AKT protein expression, inhibited NF-κB and TNF-α mRNA and protein expression, effectively reduced levels of inflammation and apoptosis-related factors, and exerted protective effects on RGCs through a bidirectional mechanism of “anti-inflammatory and pro-survival” effects.

angle-closure glaucoma  /  data mining  /  network pharmacology  /  medication patterns  /  core prescription  /  Moutan Cortex-Angelicae Sinensis Radix-Gardeniae Fructus-Bupleuri Radix-Chrysanthemi Flos-Atractylodis Macrocephalae Rhizoma-Glycyrrhizae Radix et Rhizoma-PAeoniae Radix Alba-Poria  /  quercetin  /  luteolin