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Barrier protective effects of rosmarinic acid on HMGB1-induced inflammatory responses in vitro and in vivo.

Journal of cellular physiology (2012-10-09)
Eun-Ju Yang, Sae-Kwang Ku, Wonhwa Lee, Sangkyu Lee, Taeho Lee, Kyung-Sik Song, Jong-Sup Bae
ABSTRACT

High mobility group box 1 (HMGB1) protein is a crucial cytokine that mediates response to infection, injury, and inflammation. Rosmarinic acid (RA) is an important component of the leaves of Perilla frutescens and has neuroprotective, anti-microbial, anti-oxidant, and anti-cancer effects but little is known of its effects on HMGB1-mediated inflammatory response. Here, we investigated this issue by monitoring the effects of RA on the lipopolysaccharide (LPS) or cecal ligation and puncture (CLP)-mediated release of HMGB1 and HMGB1-mediated modulation of inflammatory responses. RA potently inhibited the release of HMGB1 and down-regulated HMGB1-dependent inflammatory responses in human endothelial cells. RA also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. Furthermore, RA reduced CLP-induced HMGB1 release and sepsis-related mortality. Given these results, RA should be viewed as a candidate therapeutic agent for the treatment of various inflammatory diseases via inhibition of the HMGB1 signaling pathway.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Rosmarinic acid, ≥98% (HPLC), from Rosemarinus officinalis L.
Sigma-Aldrich
Rosmarinic acid, 96%
Rosmarinic acid, primary reference standard