Echinocystic acid inhibits acute-lung injury by inhibiting TLR4/LPS complex formation

Orally administered lancemaside A isolated from Codonopsis lanceolata Trautv. (Campanulaceae) showed anti-inflammatory effects in vivo and produced 3 metabolites by the incubation with human intestinal microflora in vitro [1, 2]. Among lancemaside A and its 3 metabolites, echinocystic acid most potently suppressed the production of the pro-inflammatory cytokines, TNF-α and IL-1β, as well as of the activation of their transcription factor NF-κB in LPS-stimulated alveola macrophages. Echinocystic acid also down-regulated the production of inflammatory markers, including inducible nitric oxide synthase and cyclooxygenase-2, as well as the inflammatory mediators, nitric oxide and prostaglandin E2 in LPS-stimulated macrophages. Echinocystic acid also inhibited the activation of IL-1 receptor-associated kinase, the phosphorylation of IKK-β and IκB-α, the nuclear translocation of NF-κB. Furthermore, echinocystic acid potently inhibited the interaction between LPS and TLR4. Echinocystic acid suppressed LPS-induced acute-lung injury in mice, as well as the expression of pro-inflammatory cytokines such as IL-1β and TNF-α, and the activation of their transcription factor, NF-κB. When lancemaside A was orally administered for mice, its metabolite echinocystic acid alone was detected in the blood. Based on these findings, echinocystic acid may express anti-inflammatory effects by inhibiting the binding of LPS to TLR4 on alveola macrophages in vitro and in vivo.

Acknowledgement: This study was supported by a grant from World Class University Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (R33–2008–000–10018–0).

References: 1. Joh EH et al. (2010) Int J Colorectal Dis 25: 545–551.

2. Joh EH et al. (2010)J Chromatogr B Analyt Technol Biomed Life Sci 878: 1875–1880.