[Effect of diosgenin on mTOR/FASN/HIF-1α/VEGFA expression in rats with non-alcoholic fatty liver disease]
- PMID: 37282950
- DOI: 10.19540/j.cnki.cjcmm.20221123.401
[Effect of diosgenin on mTOR/FASN/HIF-1α/VEGFA expression in rats with non-alcoholic fatty liver disease]
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.
Keywords: adipogenesis; diosgenin; inflammation; non-alcoholic fatty liver disease.
Similar articles
-
Effects of moxibustion with wheat-grain size cone at "Zusanli" (ST 36) on vascular injury and oxidative stress in high-fat diet rats through mTOR/HIF-1α/VEGF signaling pathway.Zhongguo Zhen Jiu. 2024 Apr 12;44(4):433-440. doi: 10.13703/j.0255-2930.20230510-k0003. Zhongguo Zhen Jiu. 2024. PMID: 38621731 Chinese, English.
-
[Diosgenin alleviates NAFLD induced by a high-fat diet in rats via mTOR/SREBP-1c/HSP60/MCAD/SCAD signaling pathway].Zhongguo Zhong Yao Za Zhi. 2023 Oct;48(19):5304-5314. doi: 10.19540/j.cnki.cjcmm.20230601.705. Zhongguo Zhong Yao Za Zhi. 2023. PMID: 38114120 Chinese.
-
[Zuogui Jiangtang Qinggan Formula improves glucolipid metabolism in type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease by regulating FoxO1/MTP/APOB signaling pathway].Zhongguo Zhong Yao Za Zhi. 2023 Aug;48(16):4438-4445. doi: 10.19540/j.cnki.cjcmm.20230317.401. Zhongguo Zhong Yao Za Zhi. 2023. PMID: 37802870 Chinese.
-
Literature review on hepatoprotective effects of diosgenin: possible mechanisms of action.Front Pharmacol. 2023 Sep 12;14:1226548. doi: 10.3389/fphar.2023.1226548. eCollection 2023. Front Pharmacol. 2023. PMID: 37767400 Free PMC article. Review.
-
The role of hypoxia-inducible factor 1α in hepatic lipid metabolism.J Mol Med (Berl). 2023 May;101(5):487-500. doi: 10.1007/s00109-023-02308-5. Epub 2023 Mar 28. J Mol Med (Berl). 2023. PMID: 36973503 Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Medical
Miscellaneous