Metabolomics approach using UHPLC/QE-MS for the mechanism of He Xue Ming Mu tablets on non-proliferative diabetic...

He Xue Ming Mu Tablets (HXMMT) are traditional Chinese medicine formulations used in clinical practice for the treatment of diabetic retinopathy. The primary purpose of this article is to illuminate the potential mechanistic pathways underlying its therapeutic efficacy in non-proliferative diabetic retinopathy. UHPLC/QE-MS was used for plasma metabolomics analysis of 10 HXMMT-treated NPDR patients, 10 untreated NPDR patients, and 10 healthy controls. To identify differential metabolites, principal component analysis (PCA) for visualizing metabolic variation and hierarchical clustering for grouping samples by metabolic profiles, were combined with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to investigate related biological pathways. Intraocular pressure (IOP), best-corrected visual acuity (BCVA), central foveal thickness (CFT), and inflammatory/angiogenic markers (IL-6, TNF-α, VEGF, Ang-2) were assessed, with correlations analyzed between altered metabolites and clinical indices. HXMMT significantly improved macular edema, reduced fundus hemorrhage, and attenuated retinal inflammation (P < 0.05). Metabolomic profiling identified a total of 813 plasma metabolites, and 283 metabolites exhibited distinct expression patterns that effectively discriminated NPDR patients from healthy controls, while 39 metabolites were found to distinguish between untreated NPDR patients and those who received HXMMT treatment. Consequently, 12 key metabolites showed significant covariance with clinical parameters of NPDR (P < 0.05), suggesting their potential role as critical mediators in the pharmacodynamic mechanism of HXMMT. HXMMT exerts therapeutic effects on NPDR by targeting 12 plasma metabolites, particularly via the glycerophospholipid metabolic axis, providing a mechanistic basis for its clinical use.