Effects and mechanism of polysaccharides from Hedyotis diffusa on isoniazid-induced liver injury
OBJECTIVE To investigate the effects and mechanism of polysaccharides from Hedyotis diffusa(HDP)on isoniazid(INH)-induced liver injury.METHODS Healthy transgenic zebrafish with liver-specific fluorescence were divided into normal group,model group(4 mmol/L INH),HDP low-concentration group(4 mmol/L INH+50 mg/mL HDP)and HDP high-concentration group(4 mmol/L INH+100 mg/mL HDP).After grouping treating,the liver fluorescence area,fluorescence intensity and pathological changes of liver tissue were observed.Human liver L02 cells were divided into normal group,model group(4 mmol/L INH),HDP low-concentration group(4 mmol/L INH+2 mg/mL HDP),and HDP high-concentration group(4 mmol/L INH + 4 mg/mL HDP).After grouping treating,the cell viability was detected,and the levels of alanine transaminase(ALT),aspartate transaminase(AST),and the content of glutathione(GSH)as well as the expression levels of silent information regulator 1(Sirt1),nuclear factor-erythroid 2-related factor 2(Nrf2),heme oxygenase-1(HO-1)and quinone oxidoreductase 1(NQO1)proteins were detected.RESULTS Compared with the model group,the HDP low-and high-concentration groups showed varying degrees of increase in the fluorescence area and fluorescence intensity(except for HDP low-concentration group)of zebrafish liver(P<0.05 or P<0.01),and the characteristics of liver injury and necrosis had been improved to varying degrees.Compared with model group,the survival rate of L02 cells,the content of GSH(except for HDP low-concentration group),the protein expression levels of Sirt1(except for HDP low-concentration group),Nrf2,NQO1,HO-1(except for HDP low-concentration group)were significantly increased in HDP low-and high-concentration groups(P<0.05 or P<0.01),and the levels of ALT and AST(except for HDP low-concentration group)were significantly decreased(P<0.05);the number of survival cells significantly increased,while the number of damaged or dead cells significantly decreased.CONCLUSIONS HDP has a potential protective effect against INH-induced liver injury,the mechanism of which may be associated with activating Sirt1/Nrf2 signaling pathway,improving mitochondrial function and enhancing antioxidant capacity.
polysaccharides from Hedyotis diffusaisoniazidliver injuryzebrafishhuman liver L02 cellSirt1/Nrf2 signaling pathway