Identification of Biomarkers for Dendrobium officinale Polysaccharide in Type 2 Diabetes Mellitus via Integrated Network Pharmacology and Mendelian Randomization

Dendrobium officinale polysaccharide (DOP) shows efficacy against type 2 diabetes (T2D), but its mechanisms remain unclear. The present investigation aimed to identify potential biomarkers associated with DOP-mediated therapeutic interventions in T2D. Datasets related to T2D were excavated from the Gene Expression Omnibus (GEO) database. Candidate genes were acquired from the intersection of genes obtained from weighted gene co-expression network analysis (WGCNA) and differential analysis. Subsequently, Mendelian randomization (MR) identified causal biomarkers, validated by Receiver Operating Characteristic (ROC) curves and expression profiling. Then, a nomogram, immune infiltration, single-cell analysis, and molecular docking were performed. Among the 12 candidate genes, 7 with available eQTL instruments were included in MR analysis, while 5 lacking genome-wide significant IVs (p < 5 × 10−8) were excluded. Three genes demonstrated significant MR associations with T2D, and biomarkers GLI1 and LGALS9 showed strong diagnostic performance and were upregulated in T2D. The nomogram had good predictive value. Seventeen immune cells differed significantly between T2D and controls, with GLI1 and LGALS9 positively correlating with most and primarily expressed in stellate cells. Finally, D-Galacturonic acid, D-Mannose, and L-rhamnose monohydrate were compounds showing predicted binding potential with candidate biomarkers GLI1 and LGALS9 emerged as promising potential molecular candidates associated with DOP-mediated T2D regulation, offering novel mechanistic perspectives on DOP’s anti-diabetic properties.