Researchers found that two chlorogenic acid compounds from the herb Artemisia lavandulaefolia can block a skin enzyme (KLK5) that normally turns a protein called cathelicidin into the inflammatory peptide LL‑37. By stopping this step, the compounds reduced inflammation signals in immune cells and also slowed the growth and movement of blood‑vessel cells that contribute to rosacea lesions. The work was done in cell cultures, not people, so it shows a promising mechanism but isn’t a proven treatment yet.

Rosacea is a chronic inflammatory disease affecting facial skin. It is associated with immune and vascular dysfunction mediated via increased expression and activity of cathelicidin and kallikrein 5 (KLK5), a serine protease of stratum corneum. Therefore, KLK5 inhibitors are considered as therapeutic agents for improving the underlying pathophysiology and clinical manifestation of rosacea. Here, we isolated the active constituents of <i>Artemisia lavandulaefolia</i> (<i>A. lavandulaefolia</i>) and investigated their inhibitory effect on KLK5 protease activity. Using bioassay-guided isolation, two bioactive compounds including chlorogenic acid isomers, 3,5-dicaffeoylquinic acid (isochlorogenic acid A) (1), and 4,5-dicaffeoylquinic acid (isochlorogenic acid C) (2) were isolated from <i>A. lavandulaefolia</i>. In this study, we evaluated the effects of isochlorogenic acids A and C on dysregulation of vascular and immune responses to rosacea, and elucidated their molecular mechanisms of action. The two chlorogenic acid isomers inhibit KLK5 protease activity, leading to reduced conversion of inactive cathelicidin into active LL-37. This inhibition of LL-37 production by isochlorogenic acids A and C reveals the efficacy of suppressing the expression of inflammatory mediators induced by LL-37 in immune cells such as macrophages and mast cells. In addition, both isomers of chlorogenic acid directly inhibited the proliferation and migration of vascular endothelial cells induced by LL-37.