Brown algae have been recognized as a food ingredient and health food supplement in Japan and Korea, and phlorotannins are unique marine phenol compounds produced exclusively by brown algae. Sepsis is a whole-body inflammatory condition with a mortality rate of 30-40%. Here, we investigated the effects of a phlorotannin-rich extract of the edible brown alga Ecklonia cava against hyper-inflammatory response in LPS-induced septic shock mouse model. E. cava extract significantly increased the survival rate and attenuated liver and kidney damage in the mice. In addition, E. cava attenuated serum levels of NO, PGE2, and HMGB-1. In macrophages, treatment with E. cava extract down-regulated iNOS, COX-2, TNF-α, IL-6, and HMGB-1. In addition, E. cava suppressed the NIK/TAK1/IKK/IκB/NFκB pathway. Moreover, E. cava increased Nrf2 and HO-1 expression. HO-1 knockdown using siRNA restored the extract-suppressed NO and PGE2 production. Dieckol, a major compound in the extract, reduced mortality, tissue toxicity, and serum levels of the inflammatory factors in septic mice. These data suggest that brown algae phlorotannins suppress septic shock through negative regulation of pro-inflammatory factors via the NIK/TAK1/IKK/IκB/NFκB and Nrf2/HO-1 pathways.
Keywords: Ecklonia cava; Nrf2/HO-1; inflammation; phlorotannin; sepsis.