Hepatoprotection mechanism against alcohol-induced liver injury in vivo and structural characterization of Pinus koraiensis pine nut polysaccharide

Abstract

Previous studies have shown that Pinus koraiensis pine nut polysaccharide PNP80b-2 exerts widely protective effects against liver injury induced by chemical pollutants, alcohol and drugs. By comparison, PNP80b-2 exhibits the strongest hepatoprotection against alcohol-induced liver injury (AILI). Thus, the purpose of this study is to investigate the hepatoprotection mechanisms of PNP80b-2 against AILI in vivo. The results indicated that PNP80b-2 alleviated oxidative stress induced by alcohol through enhancing antioxidant capacity of hepatocytes via NRF2/HO-1 pathway. PNP80b-2 also effectively suppressed the secretion of pro-inflammatory cytokines including TNF-α, IL-1β and IL-6, exhibiting anti-inflammatory effects via NF-κB signaling pathway in AILI. In addition, PNP80b-2 protected mice from severe DNA damage induced by alcohol through regulating the expression of Hipk2, P53, Hp1γ and Wip1. Taken together all the results, PNP80b-2 exerts hepatoprotective activity against AILI in vivo through enhancing antioxidant capacity, suppressing inflammation response and promoting DNA damage repair in livers. Furthermore, the structural features of PNP80b-2 were also characterized. PNP80b-2, with molecular weight of 23.0 kDa, was found to be composed of 1,2-linked Galf, 1,2-linked Rhap, 1,4-linked Xylp, 1,6-linked Glcp, 1,4-linked GlcpA, 1,2,6-linked Galp, 1,4,6-linked Glcp, 1,2,3,4-linked Arap, 1-linked Galp and Leu- and Ile-linked O-glycopeptide bonds, based on the GC–MS and NMR results.