Network Pharmacology and Molecular Docking Analysis of Luteolin from Ginkgo biloba for Drug Target Identification in Age-Related Cardiovascular Diseases

Aging is associated with an increased risk of cardiovascular diseases (CVDs), which are among the leading causes of mortality in elderly populations. Natural bioactive compounds have shown promise in mitigating cardiovascular risks. This study investigates luteolin, a flavonoid from Ginkgo biloba, known for its antioxidant, anti-inflammatory, and vasorelaxant properties, in managing age-related cardiovascular diseases (ACVDs). An integrated approach combining network pharmacology and molecular docking analysis was adopted to identify the pharmacodynamic properties and specific protein targets of luteolin in ACVD. Among 60 bioactive compounds from Ginkgo biloba screened, luteolin was selected based on its known cardioprotective properties. Through databases like DisGeNET, OMIM and GeneCards, 2,305 ACVD-related target proteins were identified, with 42 targets overlapping with luteolin. Network pharmacology analysis using STRING and Cytoscape revealed key proteins such as TP53, AKT1, JUN, TNF, and IL6 as hub protein within the protein-protein interaction network. Pathway enrichment analysis highlighted significant pathways, including the AGE-RAGE and IL-17 signaling pathways, lipid and atherosclerosis pathway, linking luteolin’s effects to mechanisms central to ACVDs. Molecular docking studies further demonstrated strong binding affinities between luteolin and key targets such as MAPK3, MAPK8, JUN, TP53 and AKT1 suggesting effective modulation of pathways involved in inflammation, oxidative stress, and apoptosis. These findings suggest that luteolin could serve as a multifaceted therapeutic agent for ACVD by targeting inflammatory and signaling pathways.