FJH-KO obtained from Antarctic krill, especially Euphausia superba, has been reported to contain high amounts of omega-3 polyunsaturated fatty acids (n-3 PUFA) and to exhibit anticancer and anti-inflammatory properties. However, its antithrombotic effects have not yet been reported. This study aimed to investigate the antithrombotic effects of FJH-KO in carrageenan-induced thrombosis mouse models and human endothelial cells. Thrombosis was induced by carrageenan injection, whereas the mice received FJH-KO pretreatment. FJH-KO attenuated carrageenan-induced thrombus formation in mouse tissue vessels and prolonged tail bleeding. The inhibitory effect of FJH-KO was associated with decreased plasma levels of thromboxane B2, P-selectin, endothelin-1, β-thromboglobulin, platelet factor 4, serotonin, TNF-α, IL-1β, and IL-6. Meanwhile, FJH-KO induced plasma levels of prostacyclin I2 and plasminogen. In vitro, FJH-KO decreased the adhesion of THP-1 monocytes to human endothelial cells stimulated by TNF-α via eNOS activation and NO production. Furthermore, FJH-KO inhibited the expression of TNF-α-induced adhesion molecules such as ICAM-1 and VCAM-1 by suppressing the NF-κB signaling pathway. Taken together, our study demonstrates that FJH-KO protects against carrageenan-induced thrombosis by regulating endothelial cell activation and has potential as an antithrombotic agent.

Although flavonoids from Scutellaria baicalensis are well known for their antioxidant properties, the active constituents and biological effects of its congeneric species, Scutellaria indica L. (S. indica), remain unclear. In this study, we investigated the antioxidant functions and cytoprotective effects of 5,2′,5′-trihydroxy-7,8-dimethoxyflavanone (TDF), a flavanone constituent of S. indica, against oxidative stress. Among six Scutellaria-derived compounds screened, TDF produced the highest antioxidant response element (ARE)-reporter activity in HepG2 cells, and it upregulated the expression of Nrf2 target genes in HaCaT cells. In an H₂O₂-induced oxidative stress model, TDF suppressed ROS and reversed the H₂O₂-induced reduction in total Nrf2 protein. Additionally, TDF showed SOD-like activity and modest elastase-inhibitory activity in cell-free assays and was classified as a non-irritant in a 3D-reconstructed human epidermis model. Overall, these results indicate that TDF is a bioactive constituent of S. indica that protects keratinocytes against oxidative stress, and that this protective effect is associated with the regulation of the Nrf2/ARE pathway.