Effect of diosgenin on mTOR/FASN/HIF-1α/VEGFA expression in rats with non-alcoholic fatty liver disease.
10.19540/j.cnki.cjcmm.20221123.401
- Author:
Guo-Liang YIN
1
;
Hong-Yi LIANG
1
;
Peng-Peng LIANG
1
;
Ya-Nan FENG
1
;
Su-Wen CHEN
1
;
Xiang-Yi LIU
1
;
Wen-Chao PAN
1
;
Feng-Xia ZHANG
2
Author Information
1. Shandong University of Traditional Chinese Medicine Ji'nan 250014, China.
2. Affiliated Hospital of Shandong University of Traditional Chinese Medicine Ji'nan 250014, China.
- Publication Type:Journal Article
- Keywords:
adipogenesis;
diosgenin;
inflammation;
non-alcoholic fatty liver disease
- MeSH:
Rats;
Male;
Animals;
Non-alcoholic Fatty Liver Disease/metabolism*;
Vascular Endothelial Growth Factor A/metabolism*;
Tumor Necrosis Factor-alpha/metabolism*;
Cholesterol, LDL;
Rats, Sprague-Dawley;
Liver;
Inflammation/metabolism*;
Diet, High-Fat/adverse effects*;
TOR Serine-Threonine Kinases/metabolism*;
RNA, Messenger/metabolism*;
Body Weight;
Mammals
- From:
China Journal of Chinese Materia Medica
2023;48(7):1760-1769
- CountryChina
- Language:Chinese
-
Abstract:
The present study aimed to investigate the effect of diosgenin on mammalian target of rapamycin(mTOR), fatty acid synthase(FASN), hypoxia inducible factor-1α(HIF-1α), and vascular endothelial growth factor A(VEGFA) expression in liver tissues of rats with non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin on lipogenesis and inflammation in NAFLD. Forty male SD rats were divided into a normal group(n=8) fed on the normal diet and an experimental group(n=32) fed on the high-fat diet(HFD) for the induction of the NAFLD model. After modeling, the rats in the experimental group were randomly divided into an HFD group, a low-dose diosgenin group(150 mg·kg~(-1)·d~(-1)), a high-dose diosgenin group(300 mg·kg~(-1)·d~(-1)), and a simvastatin group(4 mg·kg~(-1)·d~(-1)), with eight rats in each group. The drugs were continuously given by gavage for eight weeks. The levels of triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were detected by the biochemical method. The content of TG and TC in the liver was detected by the enzyme method. Enzyme-linked immunosorbent assay(ELISA) was used to measure interleukin 1β(IL-1β) and tumor necrosis factor α(TNF-α) in the serum. Lipid accumulation in the liver was detected by oil red O staining. Pathological changes of liver tissues were detected by hematoxylin-eosin(HE) staining. The mRNA and protein expression levels of mTOR, FASN, HIF-1α, and VEGFA in the liver of rats were detected by real-time fluorescence-based quantitative polymerase chain reaction(PCR) and Western blot, respectively. Compared with the normal group, the HFD group showed elevated body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1β, and TNF-α(P<0.01), increased lipid accumulation in the liver(P<0.01), obvious liver steatosis, up-regulated mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.01), and increased protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). Compared with the HFD group, the groups with drug treatment showed lowered body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1β, and TNF-α(P<0.05, P<0.01), reduced lipid accumulation in the liver(P<0.01), improved liver steatosis, decreased mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.05, P<0.01), and declining protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). The therapeutic effect of the high-dose diosgenin group was superior to that of the low-dose diosgenin group and the simvastatin group. Diosgenin may reduce liver lipid synthesis and inflammation and potentiate by down-regulating the mTOR, FASN, HIF-1α, and VEGFA expression, playing an active role in preventing and treating NAFLD.
