Wolfberry-Derived Zeaxanthin Dipalmitate Attenuates Ethanol-Induced Hepatic Damage

  • Mol Nutr Food Res. 2019 Jun;63(11):e1801339. doi: 10.1002/mnfr.201801339.
Hao Gao  1  2 ,  Yi Lv  3 ,  Yingxia Liu  4 ,  Jingjing Li  5 ,  Xiaogang Wang  6 ,  Zhengqun Zhou  1 ,  George L Tipoe  7 ,  Songying Ouyang  3 ,  Yutong Guo  8 ,  Jinhong Zhang  8 ,  Xiangfeng Hao  8 ,  Wei Li  9 ,  Kazuo Koike  9 ,  Kwok-Fai So  5 ,  Jia Xiao  2  7
Affiliations
  • 1. Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, China.
  • 2. Clinical Medicine Research Institute, The First Affiliated Hospital of Jinan University, Guangzhou, China.
  • 3. Laboratory of Neuroendocrinology, School of Biological Sciences, Fujian Normal University, Fuzhou, China.
  • 4. State Key Discipline of Infectious Diseases, Department of Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen, China.
  • 5. GMH Institute of CNS Regeneration, Guangdong Medical Key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou, China.
  • 6. Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing, China.
  • 7. School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.
  • 8. Yinchuan Bairuiyuan Biotechnology, Yinchuan, China.
  • 9. Faculty of Pharmaceutical Sciences, Toho University, Chiba, Japan.
PMID: 30938072 DOI: 10.1002/mnfr.201801339
Abstract

Scope: Besides abstinence and nutritional support, there is no proven clinical treatment for patients with alcoholic fatty liver disease (AFLD). Here, the therapeutic effects and mechanisms of action of wolfberry-derived zeaxanthin dipalmitate (ZD) on AFLD models are demonstrated.

Methods and results: The hepatoprotective effects of ZD are evaluated in vitro and in vivo. Direct interacting receptors of ZD on cell membranes are identified by liver-specific knockdown and biophysical measurements. Downstream signaling pathways are delineated using molecular and cellular biological methods. It is demonstrated that ZD attenuates hepatocyte and whole-liver injury in ethanol-treated cells (dose: 1 µm) and a chronic binge AFLD rat model (dose: 10 mg kg-1 ), respectively. The direct targets of ZD on the cell membrane include receptor P2X7 and Adiponectin Receptor 1 (adipoR1). Signals from P2X7 and adipoR1 modulate the phosphatidylinositide 3-kinase-Akt and/or AMP-activated protein kinase-FoxO3a pathways, to restore mitochondrial Autophagy (Mitophagy) functions suppressed by ethanol intoxication. In addition, ZD alleviates hepatic inflammation partially via the inhibition of NOD-like Receptor 3 inflammasome, whose activation is a direct consequence of suppressed Mitophagy. Liver-specific inhibition of receptors or Mitophagy significantly impairs the beneficial effects of ZD.

Conclusions: ZD is an effective and promising agent for the potential treatment of AFLD.

Keywords
alcoholic fatty liver disease; immediate receptor; inflammasome; mitophagy; zeaxanthin dipalmitate.
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