Carminic acid mitigates fructose-triggered hepatic steatosis by inhibition of oxidative stress and inflammatory reaction.

Abstract

Excessive fructose (Fru) consumption has been reported to favor nonalcoholic fatty liver disease (NAFLD). However, the molecular mechanism is still elusive, lacking effective therapeutic strategies. Carminic acid (CA), a glucosylated anthraquinone found in scale insects like Dactylopius coccus, exerts anti-tumor and anti-oxidant activities. Nevertheless, its regulatory role in Fru-induced NAFLD is still obscure. Here, the effects of CA on NAFLD in Fru-challenged mice and the underlying molecular mechanisms were explored. We found that Fru intake significantly led to insulin resistance and dyslipidemia in liver of mice, which were considerably attenuated by CA treatment through repressing endoplasmic reticulum (ER) stress. Additionally, inflammatory response induced by Fru was also attenuated by CA via the blockage of nuclear factor-κB (NF-κB), mitogen-activated protein kinases (MAPKs) and tumor necrosis factor α/TNF-α receptor (TNF-α/TNFRs) signaling pathways. Moreover, Fru-provoked oxidative stress in liver tissues was remarkably attenuated by CA mainly through improving the activation of nuclear factor erythroid 2-related factor 2 (Nrf-2). These anti-dyslipidemias, anti-inflammatory and anti-oxidant activities regulated by CA were confirmed in the isolated primary hepatocytes with Fru stimulation. Importantly, the in vitro experiments demonstrated that Fru-induced lipid accumulation was closely associated with inflammatory response and reactive oxygen species (ROS) production regulated by TNF-α and Nrf-2 signaling pathways, respectively. In conclusion, these results demonstrated that CA could be considered as a potential therapeutic strategy to attenuate metabolic disorder and NAFLD in Fru-challenged mice mainly through suppressing inflammatory response and oxidative stress.

• Authors: Ling Li, Bo Fang, Yinglei Zhang, Liuqing Yan, Yuxin He, Linfeng Hu, Qifei Xu, Qiang Li, Xianling Dai, Qin Kuang, Minxuan Xu, Jun Tan, Chenxu Ge
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 145 Pg. 112404 (Jan 2022) ISSN: 1950-6007 [Electronic] France
• PMID: 34781143 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• Reactive Oxygen Species
• Fructose
• Carmine

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (pharmacology)
• Carmine (pharmacology)
• Disease Models, Animal
• Dyslipidemias (drug therapy)
• Fructose
• Hepatocytes (drug effects, pathology)
• Inflammation (drug therapy, pathology)
• Insulin Resistance
• Male
• Mice
• Mice, Inbred C57BL
• Non-alcoholic Fatty Liver Disease (drug therapy, pathology)
• Oxidative Stress (drug effects)
• Reactive Oxygen Species (metabolism)