2. Academic Validation
  3. Wolfberry-Derived Zeaxanthin Dipalmitate Attenuates Ethanol-Induced Hepatic Damage

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

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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