The effect of gentiopicroside on TLR-4/NF-κB and AMPK/Nrf2 in non-alcoholic fatty liver disease

XU Qiong-mei1 GAO Ya1 LI Zi-meng1 WEI Ri-ming1 MA Xiao-hui2 JIN Ling2 ZHANG Ke-feng1

(1.Pharmacy School of Guilin Medical University, Guilin, China 5410041)
(2.College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, China 730000)
【Novelty】TLR-4/NF-κB, AMPK/Nrf2 are closely related to oxidative stress and inflammation, but the association between GPS and the TLR-4/NF-κB, AMPK/Nrf2 signaling pathways in NAFLD models has not been reported. GPS can regulate lipid metabolism, inhibit oxidative stress levels and inflammatory responses, and regulate the TLR-4/NF- κB and AMPK/Nrf2 signaling pathways to protect liver, thus providing evidence for the clinical treatment of NAFLD.
【Knowledge Link】Kupffer cell

【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;

【DOI】

【Funds】 National Natural Science Foundation of China (81860673) Guangxi Bagui Scholar Special Project (2017143)

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This Article

ISSN:1001-6880

CN: 51-1335/Q

Vol 32, No. 10, Pages 1652-1658

October 2020

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Abstract

  • 1 Materials and reagents
  • 2 Methods
  • 3 Results
  • 4 Discussion
  • References