The Protect Effects Of Phellinus Linteus Polysaccharides In Acetaminophen-induced Acute Liver Injury

Overdose of acetaminophen（APAP） is currently one of the main causes of hepatoxicity and acute liver injury,which is often linked to oxidative stress.Phellinus linteus is a well-known medicinal and edible fungus.Phellinus linteus polysaccharides（Phps） are substances in various biological activities extracted from Phellinus linteus.Phps has shown hepatoprotective effects,however,the mechanism of Phps on APAP-induced acute liver injury has not been further elucidated.The aim of this study is to investigate the underlying mechanism of Phps in acute liver injury.In vitro,HepG2cells were used to explore the effects of Phps on AMP-activated protein kinase（AMPK） and nuclear factor erythroid-2-related factor（Nrf2） signaling pathways in cells;In vivo,the mechanism of Phps was explored by APAP-induced acute liver injury in mice.Our results show that Phps can significantly activate the AMPK signaling pathway in HepG2 cells and promote Nrf2 transport into the nucleus,activating the expression of downstream proteins,thereby enhancing the antioxidant capacity of cells.Pretreatment of wild-type mice with Phps can effectively alleviate APAP-induced acute liver injury by reducing the levels of alanine aminotransferase（ALT） and aspartate aminotransferase（AST） in serum.Meanwhile,Phps significantly reduced the excessive myeloperoxidase（MPO） activity induced by APAP and remarkably increased the content of glutathione（GSH） in the liver.In addition,Phps alleviated APAP-induced histopathological changes.In order to explore the mechanism of Phps,the changes of signaling pathways in liver were detected by Western blot.As results show that Phps promoted AMPK/AKT pathway and up-regulated Nrf2 transported into the nucleus,and elevated heme oxygenase 1（HO-1）,glutamate-cysteine ligase catalytic（GCLC）,glutamate-cysteine ligase modifier（GCLM） and quinone oxidoreductase（NQO1）.Additionally,Phps apparently facilitated the expression of autophagy proteins（ATG3,ATG5,ATG7,and ATG12）.However,the protective effects of Phps on the liver were weakened in Nrf2 knockout(Nrf2^-/-) mice,there was no obvious effects diminution of ALT and AST in serum and the increased of GSH in liver,poorly histopathological improvement;the antioxidant capacity of the body weakened.Therefore,Phps alleviates APAP-induced acute liver injury by activating the antioxidant stress pathway.