Nicotinate-curcumin improves NASH by inhibiting the AKR1B10/ACCα-mediated triglyceride synthesis

作者：Xiu-Lian Lin, Yaling Zeng, Jie Ning, Zhe Cao, Lan-Lan Bu, Wenjing Liao, Zhimin Zhang, Tan-jun Zhao, Rong-geng Fu, Xuefeng Yang, Yong-Zhen Gong, Limei Lin, Deliang Cao, Caiping Zhang, Duan-Fang Liao, Yamei Li, Jianguo Zeng · 发表于：Lipids in Health and Disease · 年份：2024 · DOI：10.1186/s12944-024-02162-5 · 被引用次数：13 · 研究领域：Aldose Reductase and Taurine、Liver Disease Diagnosis and Treatment、Drug-Induced Hepatotoxicity and Protection

Abstract Background Nonalcoholic steatohepatitis (NASH) is a prevalent chronic liver condition. However, the potential therapeutic benefits and underlying mechanism of nicotinate-curcumin (NC) in the treatment of NASH remain uncertain. Methods A rat model of NASH induced by a high-fat and high-fructose diet was treated with nicotinate-curcumin (NC, 20, 40 mg·kg − 1 ), curcumin (Cur, 40 mg·kg − 1 ) and metformin (Met, 50 mg·kg − 1 ) for a duration of 4 weeks. The interaction between NASH, Cur and Aldo-Keto reductase family 1 member B10 (AKR1B10) was filter and analyzed using network pharmacology. The interaction of Cur, NC and AKR1B10 was analyzed using molecular docking techniques, and the binding energy of Cur and NC with AKR1B10 was compared. HepG2 cells were induced by Ox-LDL (25 µg·ml − 1 , 24 h) in high glucose medium. NC (20µM, 40µM), Cur (40µM) Met (150µM) and epalrestat (Epa, 75µM) were administered individually. The activities of ALT, AST, ALP and the levels of LDL, HDL, TG, TC and FFA in serum were quantified using a chemiluminescence assay. Based on the changes in the above indicators, score according to NAS standards. The activities of Acetyl-CoA and Malonyl-CoA were measured using an ELISA assay. And the expression and cellular localization of AKR1B10 and Acetyl-CoA carboxylase (ACCα) in HepG2 cells were detected by Western blotting and immunofluorescence. Results The results of the animal experiments demonstrated that NASH rat model induced by a high-fat and hig...