Protective Effects And Mechanisms Of Seabucthorn Berry Polysaccharide On Acetaminophen-induced Liver Injury In Mice

Drug-induced liver injury(DILI)is caused by the drug and its metabolites,which is the main cause of acute liver failure.Recently,the prevalence of DILI is increasing,and the prevention and treatment of DILI is very necessary.Seabuckthorn has been considered to have high medicinal values,and its berries are used to treat many kinds of diseases.However,the studies about the treatment of seabuckthorn berry polysaccharide extracts(SP)on DILI have less been clarified.This study aimed to investigate the protective effects and mechanisms of seabuckthorn berry polysaccharide extracts against acetaminophen(APAP)-induced liver injury in mice and to provide a scientific basis for the development of hepatoprotective drugs.C57BL/6 male mice were divided into six groups:control group,APAP group,N-acetylcysteine group(NAC),low dose of SP group(APAP/SP100),high dose of SP group(APAP/SP200)and SP control group(SP200).Mice in the low,high dose of SP group and the SP control group were given SP(100mg·kg-1 200mg·kg-1 and 200mg kg-1)orally for 30 consecutive days prior to APAP exposure(350mg·kg-1).NAC(150mg·kg-1)administrated 1h before APAP challenge.Mice were sacrificed 16h after APAP treatment.Serum ALT and AST were detected;Hepatic expression of GSH,SOD,MDA,NO,iNOS and GSH-PX were examined.The expression of TLR4,p-JNK,p62,Keap-1,Bcl-2,Bax,SOD-2,Nrf-2 and its target genes were detected by Western blotting;TNF-a,IL-6,IL-10 and Nrf-2 as well as its target genes HO-1,GCLC,NQO-1 were analyzed by Real-time PCR.The results showed that SP significantly decreased the level of serum ALT and AST in APAP mice,increased the hepatic SOD,GSH and GSH-PX level.SP decreased the level of MDA,NO and iNOS.The results of HE staining showed that SP alleviated APAP-induced hepatotoxicity.In addition,SP suppressed the expression of TLR4,p-JNK and increased the Bcl-2/Bax;SP inhibited TNF-a and IL-6 mRNA expression and promoted the expression of IL-10 mRNA.Furthermore,SP promoted the nuclear translocation of Nrf-2 and downregulated the expression of Keap-1.SP increased the expression of HO-1 and SOD-2..Taken together,this study illustrated that SP protects against APAP-induced liver injury by regulating TLR4-p-JNK and Nrf-2/HO-1-SOD-2 signaling pathway.The protective effects of SP were associated with its anti-inflammatory and anti-oxidative potentials.The study laid a foundation for the development of seabuckthorn polysaccharide-like green medicines.