PMID- 38114120 OWN - NLM STAT- MEDLINE DCOM- 20231221 LR - 20231221 IS - 1001-5302 (Print) IS - 1001-5302 (Linking) VI - 48 IP - 19 DP - 2023 Oct TI - [Diosgenin alleviates NAFLD induced by a high-fat diet in rats via mTOR/SREBP-1c/HSP60/MCAD/SCAD signaling pathway]. PG - 5304-5314 LID - 10.19540/j.cnki.cjcmm.20230601.705 [doi] AB - This study aims to observe the effects of diosgenin on the expression of mammalian target of rapamycin(mTOR), sterol regulatory element-binding protein-1c(SREBP-1c), heat shock protein 60(HSP60), medium-chain acyl-CoA dehydrogenase(MCAD), and short-chain acyl-CoA dehydrogenase(SCAD) in the liver tissue of the rat model of non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin in alleviating NAFLD. Forty male SD rats were randomized into five groups: a control group, a model group, low-(150 mg.kg~(-1).d~(-1)) and high-dose(300 mg.kg~(-1).d~(-1)) diosgenin groups, and a simvastatin(4 mg.kg~(-1).d~(-1)) group. The rats in the control group were fed with a normal diet, while those in the other four groups were fed with a high-fat diet. After feeding for 8 weeks, the body weight of rats in the high-fat diet groups increased significantly. After that, the rats were administrated with the corresponding dose of diosgenin or simvastatin by gavage every day for 8 weeks. The levels of triglyceride(TG), total cholesterol(TC), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were determined by the biochemical method. The levels of TG and TC in the liver were measured by the enzyme method. Oil-red O staining was employed to detect the lipid accumulation, and hematoxylin-eosin(HE) staining to detect the pathological changes in the liver tissue. The mRNA and protein levels of mTOR, SREBP-1c, HSP60, MCAD, and SCAD in the liver tissue of rats were determined by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) and Western blot, respectively. Compared with the control group, the model group showed increased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lipid deposition in the liver, obvious hepatic steatosis, up-regulated mRNA and protein expression levels of mTOR and SREBP-1c, and down-regulated mRNA and protein expression levels of HSP60, MCAD, and SCAD. Compared with the model group, the rats in each treatment group showed obviously decreased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lessened lipid deposition in the liver, ameliorated hepatic steatosis, down-regulated mRNA and protein le-vels of mTOR and SREBP-1c, and up-regulated mRNA and protein levels of HSP60, MCAD, and SCAD. The high-dose diosgenin outperformed the low-dose diosgenin and simvastatin. Diosgenin may prevent and treat NAFLD by inhibiting the expression of mTOR and SREBP-1c and promoting the expression of HSP60, MCAD, and SCAD to reduce lipid synthesis, improving mitochondrial function, and promoting fatty acid beta oxidation in the liver. FAU - Chen, Su-Wen AU - Chen SW AD - Shandong University of Traditional Chinese Medicine Ji'nan 250014, China. FAU - Yin, Guo-Liang AU - Yin GL AD - Shandong University of Traditional Chinese Medicine Ji'nan 250014, China. FAU - Song, Chao-Yuan AU - Song CY AD - Zibo Central Hospital Zibo 255000, China. FAU - Meng, De-Cheng AU - Meng DC AD - Shandong University of Traditional Chinese Medicine Ji'nan 250014, China. FAU - Yu, Wen-Fei AU - Yu WF AD - Shandong University of Traditional Chinese Medicine Ji'nan 250014, China. FAU - Zhang, Xin AU - Zhang X AD - Shandong University of Traditional Chinese Medicine Ji'nan 250014, China. FAU - Feng, Ya-Nan AU - Feng YN AD - Shandong University of Traditional Chinese Medicine Ji'nan 250014, China. FAU - Liang, Peng-Peng AU - Liang PP AD - Shandong University of Traditional Chinese Medicine Ji'nan 250014, China. FAU - Zhang, Feng-Xia AU - Zhang FX AD - Affiliated Hospital of Shandong University of Traditional Chinese Medicine Ji'nan 250014, China. LA - chi PT - English Abstract PT - Journal Article PL - China TA - Zhongguo Zhong Yao Za Zhi JT - Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica JID - 8913656 RN - 0 (Sterol Regulatory Element Binding Protein 1) RN - K49P2K8WLX (Diosgenin) RN - 0 (Chaperonin 60) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - 0 (Triglycerides) RN - 0 (RNA, Messenger) RN - AGG2FN16EV (Simvastatin) RN - EC 2.7.1.1 (mTOR protein, rat) SB - IM MH - Rats MH - Male MH - Animals MH - *Non-alcoholic Fatty Liver Disease/etiology/genetics MH - Sterol Regulatory Element Binding Protein 1/metabolism MH - Diet, High-Fat/adverse effects MH - *Diosgenin/metabolism MH - Chaperonin 60/metabolism/pharmacology/therapeutic use MH - Rats, Sprague-Dawley MH - Liver MH - Signal Transduction MH - TOR Serine-Threonine Kinases/genetics/metabolism MH - Triglycerides MH - RNA, Messenger/metabolism MH - Simvastatin/metabolism/pharmacology/therapeutic use MH - Body Weight MH - Lipid Metabolism MH - Mammals/genetics/metabolism OTO - NOTNLM OT - diosgenin OT - fatty acid beta oxidation OT - lipid synthesis OT - mitochondrial function OT - non-alcoholic fatty liver disease EDAT- 2023/12/20 06:41 MHDA- 2023/12/21 06:42 CRDT- 2023/12/19 20:43 PHST- 2023/12/21 06:42 [medline] PHST- 2023/12/20 06:41 [pubmed] PHST- 2023/12/19 20:43 [entrez] AID - 10.19540/j.cnki.cjcmm.20230601.705 [doi] PST - ppublish SO - Zhongguo Zhong Yao Za Zhi. 2023 Oct;48(19):5304-5314. doi: 10.19540/j.cnki.cjcmm.20230601.705.