The Protective Effects of Cinnamyl Alcohol Against Hepatic Steatosis, Oxidative and Inflammatory Stress in Nonalcoholic Fatty Liver Disease Induced by Childhood Obesity.

Abstract

Background: Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive intracellular lipid accumulation, oxidative stress, and inflammation. Cinnamyl alcohol (CA), one of the cinnamon extracts, has been shown to exhibit anti-oxidative and anti-inflammatory activities. We proposed that CA was beneficial to NAFLD.

Methods: Serum cytokines and components of the lipid metabolism were determined in children with NAFLD against age-matched comparisons. A NAFLD mouse model was established by high fat and high carbohydrate (HFHC) diet in male C57BL/6 mouse pups, followed by administration of CA. The effects of CA on lipid metabolism, oxidative stress, and inflammation in hepatic tissues were assessed.

Results: Abnormal lipid metabolism and inflammatory responses were observed in the children with NAFLD as compared with the controls. CA reduced the weight of obese mice without affecting food intake as well as alleviating liver injury caused by HFHC feeding. CA was found to mitigate dyslipidemia and reduce hepatic steatosis in HFHC-fed mice by down-regulating genes related to lipogenesis, including peroxisome proliferator-activated receptor gamma (PPARγ), sterol regulatory element-binding transcription factor-1c (SREBP-1c), and acetyl-CoA carboxylase 1 (ACC1). Additionally, CA treatment reversed HFHC-induced oxidative stress and inflammation, evidenced by the decreased liver reactive oxygen species (ROS), hepatic inflammatory cytokine levels, and F4/80-positive macrophage infiltration in HFHC diet mice. CA reduced the protein levels of pyrin domain-containing protein 3 (NLRP3), adapter protein apoptosis-associated speck-like protein (ASC), and caspase-1 in the liver tissues significantly.

Conclusion: CA alleviates HFHC-induced NAFLD in mice, which is associated with the amelioration in lipid metabolism, oxidative stress, and inflammation.