Apigenin Attenuates Lipopolysaccharide-Induced Endothelial Activation and Injury-Associated Phenotypes in Human Umbilical Vein Endothelial Cells.

Abstract

BACKGROUND: Sepsis represents a severe challenge in critical‑care medicine. Protecting endothelial function and alleviating microvascular inflammation and oxidative stress help reduce sepsis‑associated mortality. Apigenin, a natural flavonoid, exerts anti‑inflammatory and anti‑oxidant effects; its mechanisms against endothelial injury relevant to sepsis remain unclear. PURPOSE: This study combined computational biology and in‑vitro assays to explore potential targets of apigenin against lipopolysaccharide‑triggered endothelial dysfunction. METHODS: Network pharmacology was performed for target screening followed by GO and KEGG enrichment. Transcriptomic profiles were analyzed. Molecular docking and 100‑ns molecular dynamics simulations predicted apigenin‑protein interactions. An LPS‑stimulated HUVECs injury model was established. qRT-PCR, ELISA, flow cytometry and fluorescent probes were used to evaluate inflammation, apoptosis, reactive oxygen species and monocyte adhesion. RESULTS: A total of 104 intersecting targets were identified. AKT1, HSP90AA1, EGFR, ESR1 and HIF1A were potential core candidates, with PI3K‑Akt, TNF and HIF‑1 signaling possibly involved. Simulations predicted relatively stable apigenin‑protein complexes. At 40 μM, apigenin mitigated LPS‑provoked inflammatory response, oxidative stress, apoptosis and monocyte adhesion in HUVECs. CONCLUSION: Apigenin protects HUVECs from LPS‑induced endothelial injury possibly via multi‑target and multi‑pathway patterns. This study provides preliminary computational and in vitro evidence for further investigation of apigenin against LPS-triggered endothelial injury, with potential implications for sepsis-associated vascular damage that requires further in vivo validation.

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