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

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 Fm 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 Fm was also attenuated by CA via the blockage of nuclear factor-kappa B (NF-kappa B), mitogenactivated protein kinases (MAPKs) and tumor necrosis factor alpha/TNF-alpha receptor (TNF-alpha/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 Fm 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-alpha 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.

Automated summary

Carminic acid (CA) can effectively alleviate nonalcoholic fatty liver disease (NAFLD) induced by excessive fructose consumption, mainly through suppressing inflammatory response and oxidative stress, as well as improving dyslipidemia.