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文献信息

Nuciferine ameliorates hepatic steatosis in high‐fat diet/streptozocin‐induced diabetic mice through PPARα/PGC1α pathway

期刊名:British Journal of Pharmacology
文献编号:
文献地址: https://doi.org/10.1111/bph.14482
发表日期:20 August 2018
Background and purpose

Nuciferine, an alkaloid found in the Nelumbo nucifera leaf, alleviates dyslipidemia in vivo. However, whether it improves liver injury in diabetic conditions and the underlying mechanism is unclear. The present study aimed to investigate the effects of nuciferine on lipid and glucose metabolism in a murine model of T2DM, and to determine the underlying mechanisms of these effects.

Experimental approach

A murine model of T2DM was induced by high fat diet (HFD) feeding combined with streptozocin (STZ) injections, and the diabetic mice were treated with nuciferine. The underlying mechanism of the anti‐steatotic effect of nuciferine was further explored in HepG2 hepatocytes cultured with palmitic acid. Major signaling profiles involved in fatty acid oxidation were then evaluated.

Key results

Nuciferine restored impaired glucose tolerance and insulin resistance in the diabetic mice. Hepatic levels of total cholesterol, triglycerides and low‐density lipoprotein were significantly decreased, as well as the number of lipid droplets in the nuciferine treated mice. Furthermore, nuciferine upregulated β‐oxidation related genes in the liver of diabetic mice. Luciferase reporter cell assay showed that nuciferine directly reversed palmitic acid‐induced inhibition of PPARα transcriptional activity. Silencing peroxisome proliferator activated receptor coactivator‐1α (PGC1α) expression in HepG2 cells abolished the effects of nuciferine in accelerating β‐oxidation.

Conclusions and implications

Our results demonstrated that nuciferine improved lipid profile and attenuated hepatic steatosis in HFD/STZ‐induced diabetic mice by activating the PPARα/PGC1α pathway. Nuciferine may be a potentially important candidate in improving hepatic steatosis and the management of T2DM.

… Page 6. This article is protected by copyright. All rights reserved. Methods
Materials Nuciferine was purchased from Chengdu Biopurify
Phytochemicals Ltd. (Chengdu, China). Human insulin (Humulin? R) …
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