J Lipid Atheroscler.  2022 Sep;11(3):272-279. 10.12997/jla.2022.11.3.272.

Shinjulactone A Blocks Vascular Inflammation and the EndothelialMesenchymal Transition

• Jang Ye
• Immanuel J
• Lee Jr
• Jang Yj
• Kwon YJ
• Kwon HS
• Shin JW
• Yun S

• KMID: 2533268
• DOI: http://doi.org/10.12997/jla.2022.11.3.272

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.

Keyword

Inflammation; Atherosclerosis; Endothelial cells