Enzymatic-extractable polysaccharides from Cordyceps militaris alleviate carbon tetrachloride-induced liver injury via Nrf2/ROS/NF-κB signaling pathway

[Display omitted] •A polysaccharide (EPCMa) was obtained by enzyme-based extraction from C. militaris.•The structure of EPCMa was evaluated by GC-MS, FT-IR, HPGPC, methylation and NMR.•EPCMa possessed the antioxidant ability in vitro and in vivo.•EPCMa might regulate Nrf2/ROS/NF-κB signaling pathways against liver injury. Cordyceps militaris polysaccharides have aroused attention due to extensive physiological activities. One novel enzymatic-extractable polysaccharide, EPCMa, was obtained by chromatography column under optimum conditions. Structural characteristics analysis indicated that EPCMa consisted of → 3)-α-L-Fucp-(1→, →4)-α-D-Glcp-(1→, →2,6)-α-D-Galp-(1→, →3)-α-Glcp-(1→, →6)-β-D-Galp-(1 → and β-D-Manp-(1 → with 20792 Da. Moreover, our work further investigated the effect of EPCMa on CCl4-indued liver injury and its underlying in mice. Results showed that EPCMa activated Nrf2 pathway by up-regulating Nrf2 and HO-1 expressions to enhance antioxidant enzymes for decreasing ROS and lipid peroxidation against oxidative stress, which inhibited NF-κB p65 and IκBα phosphorylation against the releases of IL-6, TNF-α and COX-2, thereby achieving hepatoprotective effect. To sum up, activation of Nrf2 pathway and suppression of NF-κB pathway by Nrf2/ROS/NF-κB signaling pathway are the main underlying mechanisms against CCl4-induced liver injury. These results demonstrated that EPCMa might be developed as a potential functional food and natural agent against liver injury.