Flavonoid Compounds in Hippophae rhamnoides L. Protect Endothelial Cells from Oxidative Damage Through the PI3K/AKT‐eNOS Pathway

Abstract Sea buckthorn, a traditional medicinal plant, has been used for several years in China for the prevention and treatment of various diseases, a practice closely associated with its significant antioxidant activity. The aim of this study was to investigate the protective effects of sea buckthorn flavonoids on vascular endothelial cells in an oxidative stress environment. We isolated and extracted active compounds from sea buckthorn and investigated their impact on endothelial nitric oxide synthase (eNOS) activity through the PI3K/AKT‐eNOS signaling pathway through a combination of network pharmacology and cellular experiments, elucidating the regulatory effects of these compounds on endothelial cell functions. Three flavonoids, named Fr.4‐2‐1, Fr.4‐2‐2 and Fr.4‐2‐3, were obtained from sea buckthorn. The results of network pharmacology indicated that they might exert their effects by regulating the PI3K‐AKT signaling pathway. In vitro results showed that all three flavonoids were effective in alleviating the degree of oxidative stress in cells, among which Fr.4‐2‐1 exerted its antioxidant effects by modulating the PI3K/AKT‐eNOS pathway. Flavonoids in sea buckthorn can effectively inhibit oxidative stress‐induced cellular damage, preserving the integrity and functionality of endothelial cells, which is crucial for maintaining vascular health and function.