Mechanism of total Ginkgo biloba flavone mediating the inflammation and autophagy in lipopolysaccharide-induced human coronary artery endothelial cells through TLR4/PI3K signaling pathway

The mechanism of total Ginkgo biloba flavonoids (GBF) on lipopolysaccharide (LPS)-induced inflammation damage and excessive autophagy in human coronary artery endothelial cells (HCAECs) was investigated. Total GBF was extracted, and its scavenging abilities for DPPH·, ABTS+, and ·OH free radicals were assessed. LPS-stimulated HCAECs served as the atherosclerotic inflammatory model (control). Treatment groups received total GBF extracts at 1 (LD-GBF), 10 (MD-GBF), or 100 μg/mL (HD-GBF). Cell proliferation and apoptosis rates were measured. Interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) levels and immunofluorescence staining was implemented for examining the light chain 3 beta (LC3B) level in HCAECs. Protein imprinting examined the expressions of LC3B, Beclin1, Toll-like receptor 4 (TLR4), and phosphatidylinositol 3-kinase (PI3K). Total GBF scavenged the DPPH·, ABTS+, and ·OH free radicals, with half-inhibitory concentrations of 0.65, 0.12, and 0.38 mg/mL, respectively. LPS group exhibited reduced cell proliferation vitality, increased cell apoptosis rate, elevated IL-6, IL-8, and TNF-α, and downregulated LC3B II/I, Beclin1 versus control group ( P < 0.05). LPS upregulates TLR4 and PI3K, while GBF dose dependently reduced their expression. LD-GBF, MD-GBF, and HD-GBF groups demonstrated increased cell proliferation vitality, decreased cell apoptosis rate, lowered IL-6, IL-8, and TNF-α, and reduced downregulated LC3B II/I, Beclin1, TLR4, and PI3K versus LPS group ( P < 0.05), exhibiting a concentration-dependent pattern. GBF treatment attenuated the excessive upregulation of LC3B II/I and Beclin1 in a dose-dependent manner. GBF selectively attenuated LPS-induced excessive autophagy while preserving basal autophagy, normalizing LC3B II/I and Beclin1 to control levels. It enhanced proliferation, reduced apoptosis, and mitigated LPS-driven inflammation and autophagic dysregulation in HCAECs via the TLR4/PI3K axis. These findings suggest GBF's therapeutic potential for atherosclerosis by targeting endothelial inflammation and autophagy, offering a novel CVD intervention strategy.