2. Academic Validation
  3. Nuciferine Alleviates High-Fat Diet- and ApoE-/--Induced Hepatic Steatosis and Ferroptosis in NAFLD Mice via the PPARα Signaling Pathway

Nuciferine Alleviates High-Fat Diet- and ApoE-/--Induced Hepatic Steatosis and Ferroptosis in NAFLD Mice via the PPARα Signaling Pathway

  • J Agric Food Chem. 2024 Nov 6;72(44):24417-24431. doi: 10.1021/acs.jafc.4c04929.
Jiannan Qiu 1 2,  Yifei Le 1,  Nian Liu 1,  Lin Chen 1,  Yuwei Jiang 1,  Yuhao Wang 3,  Xiaohui Fan 4,  Xianglu Rong 5,  Zhiling Yu 6,  Songtao Li 2,  Xiaobing Dou 1
Affiliations

Affiliations

  • 1 School of Life Science, Zhejiang Chinese Medical University, No. 548 Binwen Road, Binjiang District, Hangzhou, Zhejiang 310053, China.
  • 2 School of Public Health, Zhejiang Chinese Medical University, No. 548 Binwen Road, Binjiang District, Hangzhou, Zhejiang 310053, China.
  • 3 Zhejiang Provincial Key Laboratory of Pancreatic Disease of The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, 268 Kaixuan Road, Shangcheng District, Hangzhou, Zhejiang 310020, China.
  • 4 Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, No. 38 Zheda Road, Hangzhou, Zhejiang 310027, China.
  • 5 Chinese Medicine Institute, Guangdong Pharmaceutical University, No. 280 Outer Ring East Road, University Town, Guangzhou, Guangdong 510006, China.
  • 6 Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon Tong, Hong Kong 999077, China.
PMID: 39445611 DOI: 10.1021/acs.jafc.4c04929
Abstract

Nonalcoholic fatty liver disease (NAFLD) causes significant global mortality and healthcare costs with no recommended pharmacological intervention for clinical management. Nuciferine (Nuc) is an alkaloid with aromatic rings, abundantly found in Nelumbo nucifera Gaertn. In this study, we explored the protective mechanisms of Nuc against hepatic steatosis and Ferroptosis in NAFLD. High-fat diet (HFD) and healthy male apoE-/- mice were used to induce NAFLD and a hypercholesterolemia model. Nuc was administered to the mice for four consecutive weeks from the ninth week. Various assessments, including histopathology, RNA Sequencing, lipid metabolism, and ferroptosis-related protein expression, showed that Nuc alleviated hepatic steatosis and Ferroptosis. We further showed that Nuc improves fatty acid accumulation and Ferroptosis through the PPARα signaling pathway in mice and RSL3-treated AML-12 cells. The PPARα Inhibitor GW6471 blocked Nuc's protective effects, leading to excess accumulation of iron ions. Thus, Nuc may be a potential therapeutic agent for NAFLD.

Keywords

PPARα; ferroptosis; hepatic steatosis; nonalcoholic fatty liver disease; nuciferine.

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