The effect of gentiopicroside on TLR-4/NF-κB and AMPK/Nrf2 in non-alcoholic fatty liver disease
(2.College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, China 730000)
【Abstract】To explore the protective effect of gentiopicroside (GPS) on non-alcoholic fatty liver disease (NAFLD) rats and the effect on TLR-4/NF-κB and AMPK/Nrf2 pathways, we randomly assigned SD rats into normal group, model group, metformin group (200 mg/kg), and GPS high-, medium-, and low-dose groups (120, 60, and 30 mg/kg, respectively). The normal group was fed standard diet and the other groups were fed high-fat diet for 14 weeks to establish NAFLD model. Biochemical methods were used to detect the liver function, oxidative stress, and lipid accumulation. Enzyme-linked immunosorbent assay (ELISA) was used to detect insulin resistance and inflammatory factor levels. Western blotting was carried out to detect the expression of proteins in TLR-4/NF-κB and AMPK/Nrf2 pathways. Oil red O staining was used to observe the pathological changes of liver tissue. The results showed GPS reduced the activity or content of alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), cholesterol (TC), triglyceride (TG), total low density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBG), fasting insulin (FINS) and insulin resistance index (HOMA-IR), enhanced the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and high density lipoprotein cholesterol (HDL-C), reduced the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), NF-κBp-p65, and TLR-4 in the liver, increased the expression of p-AMPK and Nrf2. In conclusion, the mechanism of GPS to improve NAFLD may be related to the inhibition of oxidative stress and inflammatory response, and the regulation of TLR-4/NF-κB and AMPK/Nrf2 signaling pathways.
【Keywords】 gentiopicroside; non-alcoholic fatty liver; oxidative stress; inflammatory response; TLR-4/NF-κB pathway; AMPK/Nrf2 pathway;
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