Purendan alleviates non-alcoholic fatty liver disease in aged type 2 diabetic rats via regulating mTOR/S6K1/SREBP-1c signaling pathway

• Published in: Biomedicine & pharmacotherapy Vol. 148; p. 112697
• Main Authors: Fan, Lu, Niu, Hongjuan, Zhao, Linyi, Yao, Rongfei, He, Xu, Lu, Binan, Pang, Zongran
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.04.2022; Elsevier
• Subjects: Aged; Animals; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diet, High-Fat - adverse effects; Fat synthesis; Humans; Insulin resistance; Lipid Metabolism; Liver - metabolism; MTOR; NAFLD; Non-alcoholic Fatty Liver Disease - metabolism; Rats; Rats, Sprague-Dawley; Signal Transduction; SREBP-1c; Sterol Regulatory Element Binding Protein 1 - metabolism; T2DM; TOR Serine-Threonine Kinases - metabolism; FFA; T2DM; NAFLD; PRD; ALT; Fat synthesis; FBG; MDA; INS; GLU; HDL; LDL; STZ; AST; IR; SOD; SREBP-1c; MTOR; TC; S6K1; HOMA-IR; TG; Insulin resistance; OGTT; Met; HE
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2022.112697

Older people are more likely to develop insulin resistance and lipid metabolism disorders. Purendan (PRD) is a clinically verified traditional Chinese medicine compound, which plays an obvious role in regulating lipid metabolism disorder and improving insulin sensitivity. Our study aimed to investigate the efficacy and mechanism of PRD on aged type 2 diabetes mellitus (T2DM) complicated with non-alcoholic fatty liver disease (NAFLD) rats. Sprague-Dawley rats (13 months) were fed with high-fat diet (HFD) and injected with low-dose STZ to replicate T2DM model. PRD was treated at three concentrations with metformin as a positive control. After administration, blood and liver tissue samples were collected to measure glucose metabolism indexes such as serum glucose and insulin, as well as lipid metabolism indexes such as TC, TG, LDL, HDL and FFA. Liver fat accumulation was observed by HE staining and oil red O staining. And protein expression levels of mTOR, p-mTOR, S6K1, p-S6K1 and SREBP-1c were detected by western blot. After PRD treatment, not only the insulin sensitivity and insulin resistance were significantly improved, but also the TC, TG, LDL, FFA, AST and ALT in serum and the lipid accumulation in liver tissue were significantly decreased. Moreover, PRD significantly down-regulated the expression of p-mTOR, p-S6K1 and SREBP-1c in liver tissues. In conclusion, PRD can alleviate NAFLD in aged T2DM rats by inhibiting the mTOR /S6K1/ SREBP-1c pathway.