Network pharmacology reveals the underlying mechanisms of Dendrobium officinale on cardiovascular diseases: A perspective from myocardial infarction and intracerebral hemorrhage

Dendrobium officinale (DEN) has long been a medicinal and functional food resource in China. This study employed network pharmacology to reveal its mechanisms of action in the treatment of cardiovascular diseases (CVDs), including myocardial infarction (MI) and hemorrhagic cerebrovascular diseases (HCD). The active ingredients of DEN were identified by liquid chromatography‑tandem mass spectrometry (LC‑MS/MS) and screened using the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP). Functional enrichment analysis and gene set enrichment analysis were performed to identify enriched pathways, followed by molecular docking, single-cell RNA sequencing (scRNA-seq) analysis, and experimental verification. Two active ingredients of DEN, quercetin and wogonin, were identified, corresponding to 100 and 25 potential targets, respectively. A total of 390 and 363 DEGs were screened between MI and HCD samples, and were intersected with the potential targets of quercetin and wogonin. Functional enrichment analysis of targets associated with the two core targets, matrix metalloproteinase-9 ( MMP9 ) and glycogen phosphorylase L ( PYGL ), revealed enrichment in pathways related to the cellular matrix and neutrophil degranulation. GSEA showed that samples stratified by high or low expression of MMP9 and PYGL were predominantly enriched in inflammation-related pathways. Quercetin showed strong binding to MMP9 . scRNA-seq data confirmed the expression of PYGL and MMP9 at single-cell resolution. Furthermore, silencing MMP9 in modeled AC16 cells attenuated injury and promoted proliferation. This study showed that the active compounds of DEN may exert therapeutic effects on MI and HCD through multiple mechanisms, thereby supporting the efficacy of DEN in treating CVDs.