Shinjulactone A Blocks Vascular Inflammation and the Endothelial-Mesenchymal Transition

Area of Science:

• Cardiovascular Biology
• Natural Product Chemistry
• Immunology

Background:

• Endothelial inflammation, driven by nuclear factor-kappa B (NFκB), is a critical process in the development of atherosclerosis.
• Monocyte recruitment to the endothelium and endothelial-mesenchymal transition (EndMT) are key contributors to plaque instability and progression.

Purpose of the Study:

• To screen natural compounds for their ability to inhibit interleukin-1β (IL-1β)-induced endothelial inflammatory signaling.
• To investigate the therapeutic potential of shinjulactone A in preventing endothelial inflammation and EndMT.

Main Methods:

• Screening of 880 natural compounds from medicinal plants using IL-1β-stimulated endothelial cells.
• Assay of NFκB activation, monocyte adhesion, and endothelial cell viability.
• Evaluation of EndMT markers and morphology.

Main Results:

• Shinjulactone A potently inhibited IL-1β-induced NFκB activation (IC50 ≈ 1 µM) and monocyte recruitment in endothelial cells.
• Shinjulactone A did not affect lipopolysaccharide-induced NFκB activation in macrophages, preserving innate immunity.
• Unlike Bay 11-782, shinjulactone A showed no cytotoxicity and significantly inhibited EndMT.

Conclusions:

• Shinjulactone A is a promising candidate for atherosclerosis treatment due to its dual action on endothelial inflammation and EndMT.
• Its safety profile, sparing macrophage NFκB activity, supports its potential as a targeted therapeutic agent.