Effect and mechanism of asperuloside on liver fibrosis in non-alcoholic fatty liver rats
- VernacularTitle:车叶草苷对非酒精性脂肪性肝病大鼠肝纤维化的影响及机制
- Author:
Jin LIANG
1
;
Dan XU
1
;
Jinjun DU
1
Author Information
1. Dept. of Spleen,Stomach and Hepatobiliary Diseases,Wuhan Hospital of Traditional Chinese Medicine,Wuhan 430010,China
- Publication Type:Journal Article
- Keywords:
asperuloside;
non-alcoholic fatty liver disease;
liver fibrosis;
SphK1/S1P signaling pathway
- From:
China Pharmacy
2024;35(17):2102-2107
- CountryChina
- Language:Chinese
-
Abstract:
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.