Shinjulactone A Blocks Vascular Inflammation and the EndothelialMesenchymal Transition
10.12997/jla.2022.11.3.272
- Author:
Ye-eun JANG
1
;
Jenita IMMANUEL
;
Jin-ri LEE
;
Yu-jin JANG
;
Yun Ju KWON
;
Hyun Sook KWON
;
Jung-Woog SHIN
;
Sanguk YUN
Author Information
1. Department of Biotechnology, Inje University, Gimhae, Korea
- Publication Type:Original Article
- From:Journal of Lipid and Atherosclerosis
2022;11(3):272-279
- CountryRepublic of Korea
- Language:English
-
Abstract:
Objective:The endothelial inflammatory response plays an important role in atherogenesis by inducing nuclear factor (NF)κB-dependent cell adhesion molecule expression and monocyte recruitment. Here, we screened for natural ligands and investigated the ability of shinjulactone A to inhibit interleukin-1β (IL-1β)-induced endothelial inflammatory signaling.
Methods:The natural compound library included 880 single compounds isolated from medicinal plants by the Korean Medicinal Material Bank. Primary endothelial cells were pretreated with single compounds before stimulation with IL-1β to induce endothelial inflammation. Endothelial inflammation was measured by assaying NFκB activation and monocyte adhesion. The endothelial-mesenchymal transition (EndMT) was evaluated using cell type-specific marker protein expression and morphology.
Results:Shinjulactone A was identified as an efficient blocker of IL-1β -induced NFκB activation, with a half-maximal inhibitory concentration of approximately 1 µM, and monocyte recruitment in endothelial cells. However, it did not affect lipopolysaccharideinduced NFκB activation in macrophages. Compared to Bay 11-782, a well-known NFκB inhibitor that shows considerable cytotoxicity during long-term treatment, shinjulactone A did not affect endothelial cell viability. Furthermore, it also significantly inhibited the EndMT, which is known to promote atherosclerosis and plaque instability.
Conclusion:We suggest that shinjulactone A may be an effective and safe drug candidate for atherosclerosis because it targets and inhibits both endothelial inflammation and the EndMT, without impairing NFκB-dependent innate immunity in macrophages.
