Hepatoprotection of pine nut polysaccharide via NRF2/ARE/MKP1/JNK signaling pathways against carbon tetrachloride-induced liver injury in mice

Previously, we obtained a purified polysaccharide (PNP40c-1) from Pinus koraiensis pine nut and reported its protective effect on carbon tetrachloride (CCl 4 )-induced liver injury in vitro . The object of this study is to investigate its hepatoprotective activity in vivo and elucidate the mechanism underlying the hepatoprotection . PNP40c-1 effectively prevented the accumulation of serum liver injury biomarkers including alanine aminotransferase , aspartate aminotransferase, alkaline phpsphatase and total bilirubin stimulated by CCl 4 . The pathological changes in PNP40c-1-treated mice livers were also markedly ameliorated. Results showed that PNP40c-1 suppressed the production of reactive oxygen species (ROS) and lipid peroxidation, upregulated Nrf2/ARE pathway and enhanced the antioxidant capacity of hepatocytes. Furthermore, the reaction between Nrf2 and ARE promoted the generation of Mkp1 , which inhibited the activation of JNK induced by CCl 4 , and suppressed hepatocytes apoptosis by regulating the protein expression of Bax, cleaved-Caspase-3 and Bcl2, exerting hepatoprotective activity. Taken together, upregulation of Nrf2/ARE pathway and suppression of JNK activation via Nrf2/ARE/Mkp1/JNK signaling pathways are the main mechanisms underlying the hepatoprotective effect of PNP40c-1 against CCl 4 -induced mice liver injury. These results indicated that PNP40c-1 has potential to serve as a hepatoprotective agent against chemical induced hepatotoxicity.