Endothelial dysfunction, linked to reduced eNOS expression and nitric oxide (NO) availability, contributes to cardiovascular diseases (CVDs). Large cardamom exhibits antihypertensive effects by augmenting NO levels and antioxidant activity. To decipher its mechanisms, selected constituents were docked with eNOS-associated target genes such as GTP cyclohydrolase I (GTPCH-1) and (dihydrofolate reductase [DHFR]). Endothelial damage induced by L-NAME and fructose was countered by assessing nitric oxide metabolites (NOx), tetrahydrobipterin (BH4 levels), GCH-I expression and super oxide dismutase (SOD) activity after constituent incubation. Cyanidin-3-O-glucoside and petunidin-3-O-glucoside notably restored impaired vascular markers in both models. These phytoconstituents are likely to activate GCH-BH4-eNOS pathways, upregulating SOD and NO expression, maintaining endothelial integrity. Large cardamom's antihypertensive effects may stem from these components, synergistically enhancing endothelial NO release via the eNOS pathway.
Keywords: CVDs; Endothelium; large cardamom; nitric oxide synthase.