Polysaccharides from Enteromorpha prolifera protect against carbon tetrachloride-induced acute liver injury in mice via activation of Nrf2/HO-1 signaling, and suppression of oxidative stress, inflammation and apoptosis.

To investigate whether polysaccharides from Enteromorpha prolifera (EPP) could protect against acute hepatic injury induced by CCl, ICR mice were pretreated with EPP (150, 300, and 450 mg kg) and silymarin (100 mg kg) for 28 days before CCl induction. Pretreatment with EPP attenuated CCl-induced elevated serum transaminase activities and histopathological alterations in the liver. In addition, EPP prevented CCl-induced reduction of protein levels of phosphorylated nuclear factor E2-related factor 2 (p-Nrf2)/Nrf2, heme oxygenase-1 (HO-1), and mRNA levels of NADPH quinineoxidoreductase-1 (NQO-1), which, in turn, reduced hepatic oxidative stress injury. Furthermore, the hepatic protein levels of inflammatory mediators and the phosphorylation of nuclear factor-kappaB p65 (NF-κB p65) and I kappaB alpha (IκBα), and the mRNA levels of Toll-like receptor 2 (TLR2), TLR4, and prolyl-isomerase-1 (Pin-1) in the inflammatory signaling pathway were recovered in the EPP pretreated groups. Moreover, EPP prevented the hepatocellular apoptotic changes with inhibition of B-cell lymphoma 2 (Bcl-2), and the induction of Bcl-2-associated X (Bax) and Cleaved caspase-3 caused by CCl. Taken together, these results indicated that EPP protected against hepatic injury induced by CCl-derived reactive intermediates through the activation of Nrf2/HO-1 signaling, and suppression of oxidative stress, inflammation and apoptosis.