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

Abstract

To investigate whether polysaccharides from Enteromorpha prolifera (EPP) could protect against acute hepatic injury induced by CCl₄, ICR mice were pretreated with EPP (150, 300, and 450 mg kg⁻¹) and silymarin (100 mg kg⁻¹) for 28 days before CCl₄ induction. Pretreatment with EPP attenuated CCl₄-induced elevated serum transaminase activities and histopathological alterations in the liver. In addition, EPP prevented CCl₄-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 CCl₄. Taken together, these results indicated that EPP protected against hepatic injury induced by CCl₄-derived reactive intermediates through the activation of Nrf2/HO-1 signaling, and suppression of oxidative stress, inflammation and apoptosis.