Wolfberry‐Derived Zeaxanthin Dipalmitate Attenuates Ethanol‐Induced Hepatic Damage

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).

Zeaxanthin: Metabolism, Properties, and Antioxidant Protection of Eyes, Heart, Liver, and Skin

“…Similar protective effects were reported by Gao et al [90]. In this study, seven-week-old male Sprague-Dawley rats were fed a liquid diet, and one group had alcohol added progressively.…”

Role and Mechanisms of Mitophagy in Liver Diseases

“…The genetic depletion of Parkin accelerates acute and chronic and also, acute alcohol binge-induced liver injury and steatosis, which is likely due to impaired mitophagy in hepatocytes [114]. Compounds that are able to restore mitophagy inhibited by alcohol are able to attenuate liver injury in chronic alcohol feeding models [115,116]. These results indicate the protective role of mitophagy in alcoholic liver injury, and how targeting mitophagy may be a prospective therapeutic approach of ALD [117,118].…”

“…Decompensated mitophagy causes the release of mitochondrial damage-associated molecular patterns (mtDAMPs) that promote inflammatory and profibrogenic response, which in turn impair hepatic mitophagy, contributing to the pathological progression of ALD [121]. Impaired mitophagy was reported in the majority of chronic alcohol feeding cases [115,116,122], underscoring its potential critical role in the pathogenesis of ALD. Interestingly, mitochondrial fission protein Drp1 was activated in primary mouse hepatocytes treated with ethanol for 48 h, leading to mitochondrial fragmentation, which is associated with depressed FUNDC1-mediated mitophagy [122].…”

“…ALD [114,116,119,122] NAFLD [134,140] DILI [155,157,159] HBV/HCV [192] Cancer [216] The expression level of fluorescent proteins varies in different cells/tissues Not robust and easy to be dependent on individuals who are performing the quantification. Also, the half-life of the red puncta in the lysosomes may be dependent on cellular context and conditions, e.g., the activities of the lysosomal proteases NAFLD [86] DILI [159] Cancer [216] 6.…”

Zeaxanthin Dipalmitate in the Treatment of Liver Disease

“…Finally, as ethanol induces hepatocyte apoptosis, ZD downregulated the mRNA expressions of proapoptosis genes Bax-1 and caspase-3/7 and upregulated the expression of Bcl-2 [59]. Another study [99] established the ability of ZD to ameliorate liver histology in the ALFD model and decrease serum levels of ALT and AST. The authors showed ZD binding to two receptors, P2X7 and adipoR1, which in turn induced mitophagy.…”