Effect and mechanism of asperuloside on liver fibrosis in non-alcoholic fatty liver rats
OBJECTIVE To investigate the effect and mechanism of asperuloside on liver fibrosis in non-alcoholic fatty liver disease(NAFLD)rats by regulating the sphingosine kinase 1(SphK1)/sphingosine-1-phosphate(S1P)signaling pathway.METHODS SD rats were fed with a high-fat diet to establish a NAFLD model.They were randomly separated into model group,asperuloside low-dose group(14 mg/kg,i.g.,similarly hereinafter),asperuloside high-dose group(28 mg/kg),high dose of asperuloside(28 mg/kg)+pc-NC(empty plasmid,50 µg,via tail vein,similarly hereinafter)group,and high dose of asperuloside(28 mg/kg)+pc-SphK1(SphK1 overexpression plasmid,50 µg)group,with 12 rats in each group.Another 12 rats were fed with a normal diet as control group.Each group was given relevant medicine or plasmid intragastrically once a day or via tail vein twice a week,for 3 consecutive weeks.After the last medication,the levels of blood lipid indexes[total cholesterol(TC),triglyceride(TG),and free fatty acid(FFA)]and liver function indexes[aspartate transaminase(AST)and alanine transaminase(ALT)]were detected in each group.The pathological changes of liver tissue and liver fibrosis in rats were also observed in each group.The levels of serum fibrosis-related factors[procollagen type Ⅲ(PCⅢ),collagen type Ⅳ(Ⅳ-Col),laminin(LN)],pro-fibrotic factor[transforming growth factor-β1(TGF-β1)],and pro-inflammatory factors[interleukin-1β(IL-1β),inducible nitric oxide synthase(iNOS),IL-6]of rats were determined in each group.The expressions of collagen formation-related proteins(Ⅰ-Col,Ⅳ-Col)and SphK1/S1P pathway-related proteins in the liver tissues of rats were detected in each group.RESULTS Compared with control group,the liver tissue of rats in model group showed significant pathological damage;the NAFLD activity score,liver tissue collagen volume fraction,serum levels of TC,TG,FFA,AST,ALT,PCⅢ,Ⅳ-Col,LN,TGF-β1,IL-1β,iNOS and IL-6,and protein expressions of Ⅰ-Col,Ⅳ-Col,SphK1 and S1P in liver tissue were greatly increased(P＜0.05).Compared with the model group,the liver tissue pathological damage symptoms of rats in asperuloside low-dose and high-dose groups were improved,and the above indexes were all reduced significantly(P＜0.05);moreover,the high-dose group had a better effect(P＜0.05).Compared to asperuloside high-dose group,high dose of asperuloside+pc-NC group,the pathological damage of liver tissue symptoms in rats were aggravated in high dose of asperuloside+pc-SphK1 group,and the above indexes were all increased significantly(P＜0.05).CONCLUSIONS Asperuloside can reduce the expressions of pro-fibrotic factor,pro-inflammatory factors and collagen formation-related proteins by inhibiting the activity of SphK1/S1P signaling pathway,thus alleviating liver fibrosis in NAFLD rats.
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