Chlorogenic Acid Isomers Isolated from Artemisia lavandulaefolia Exhibit Anti-Rosacea Effects In Vitro.

Kyung-Baeg Roh,Deokhoon Park,Eunsun Jung,Eunae Cho,Dae-Hyuk Kweon,Youngsu Jang

doi:10.3390/biomedicines10020463

Kyung-Baeg Roh, Deokhoon Park + Show 4 more

Open Access

https://doi.org/10.3390/biomedicines10020463

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Abstract

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 Artemisia lavandulaefolia (A. lavandulaefolia) 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 A. lavandulaefolia. 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.

Highlights

30 members of the Cathelicidin family have been identified in mammalian species
This result confirmed that A. lavandulaefolia extract (ALE) regulates the transformation of cathelicidin into active LL-37 by regulating kallikrein 5 (KLK5) protease activity, but not KLK5 expression
Cathelicidin expression correlates with effective innate immune defense of the skin in chronic inflammatory diseases of skin [34]

Summary

Introduction

30 members of the Cathelicidin family have been identified in mammalian species. CAMP is the only cathelicidin gene encoding the inactive precursor protein, human cationic antibacterial protein of 18 kDa (hCAP18), which is the highly conserved cathelin domain and antimicrobial c-terminal domain [1]. The antimicrobial peptide LL-37 is generated via proteolytic processing of cathelicidin hCAP18 by stratum corneum serine protease, kallikrein 5 (KLK5), in the human epidermis, and mediates the innate defense mechanism against invading pathogens via direct lethal effect against microbes, resulting in immune cell function [2]. This function serves as a signal initiating adaptive immune defense. Rosacea lesions expressed elevated KLK5 in the basal layer of epidermis along with cathelicidin, in contrast to healthy skin, expressing reduced levels of cathelicidin and KLK5 superficially [6]

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