Danggui Shaoyaosan Regulates Autophagy via AMPK/mTOR/ULK1 Signaling Pathway in Rat Model of Metabolism-associated Fatty Liver Disease
10.13422/j.cnki.syfjx.20231336
- VernacularTitle:当归芍药散对MAFLD大鼠AMPK/mTOR/ULK1自噬信号通路的调节作用
- Author:
Yaning BIAO
1
;
Chenxu LIU
1
;
Yixin ZHANG
1
;
Yi XIAO
1
;
Ziheng WEI
2
;
Zehe YU
1
;
Ran CAO
1
Author Information
1. International Joint Research Center on Resource Utilization and Quality Evaluation of Traditional Chinese Medicine(TCM)of Hebei Province,Hebei University of Chinese Medicine, Shijiazhuang 050200,China
2. Hebei Hospital of TCM, Shijiazhuang 050011, China
- Publication Type:Journal Article
- Keywords:
Danggui Shaoyaosan;
metabolism-associated fatty liver disease (MAFLD);
adenosine monophosphate-activated protein kinase (AMPK);
mammalian target of rapamycin (mTOR);
Unc-51-like kinase-1 (ULK1);
autophagy
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2024;30(2):9-16
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the regulatory effect of Danggui Shaoyaosan on adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/Unc-51-like kinase-1 (ULK1) signaling pathway in the rat model of metabolism-associated fatty liver disease (MAFLD). MethodSixty SD rats were randomized into control, model, western medicine (polyene phosphatidylcholine capsules,0.144 g·kg-1), and low-, medium-, and high-dose (2.44, 4.88, 9.76 g·kg-1, respectively) Danggui Shaoyaosan groups. After being fed with a high-fat diet for 8 weeks, the rats in each group were administrated with corresponding drugs for 4 weeks. At the end of drug treatment, serum and liver tissue were collected for subsequent determination of related indicators. ResultCompared with the control group, the model group showed increased contents of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum, increased contents of TC, TG, and free fatty acids (FFAs) in the liver (P<0.01), and decreased content of high-density lipoprotein cholesterol (HDL-C) in the serum (P<0.01). Furthermore, the model group showed down-regulated protein levels of p-AMPK, microtubule-associated protein 1 light chain 3B (LC3B) Ⅱ, Beclin1, and ULK1 (P<0.01) and up-regulated protein levels of p-mTOR and ubiquitin-binding protein p62 in the liver (P<0.01). The hepatic steatosis was obvious and the NAFLD activity score (NAS) and oil red O staining area increased in the model group, (P<0.05, P<0.01). Compared with the model group, Danggui Shaoyaosan reduced the contents of TC and TG and the activities of ALT and AST in the serum, lowered the levels of TC, TG, and FFA in the liver, down-regulated the protein levels of p-mTOR and p62 (P<0.01), elevated the serum HDL-C level, and up-regulated the protein levels of p-AMPK, LCBⅡ, Beclin1, and ULK1 in the liver (P<0.05, P<0.01). Moreover, it alleviated hepatic steatosis and decreased the NAS and oil red O staining area (P<0.05, P<0.01). ConclusionDanggui Shaoyaosan has therapeutic effect on MAFLD rats by regulating AMPK/mTOR/ULK1 signaling pathway to enhance autophagy.