Aucubin inhibited lipid accumulation and oxidative stress via Nrf2/HO-1 and AMPK signalling pathways.

Abstract

Aucubin (AU) is the main active ingredient of Aucuba japonica which has showed many positive effects such as anti-inflammation and liver protection. Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. In this research, we explored the effects of AU on the tyloxapol-induced NAFLD in mice and apolipoprotein C-III (apoC-III) induced-3T3L1 cells. Tyloxapol (300 mg/kg) was injected to C57BL/6 mice with aucubin. The differentiated 3T3-L1 cells were treated with or without aucubin after stimulation of apoC-III (100 μg/mL). In results, aucubin inhibited hyperlipidaemia, oxidative stress and inflammation by influencing the content of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), very low density lipoprotein (VLDL), myeloperoxidase (MPO), superoxide dismutase (SOD), tumour necrosis factor receptor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 in blood. AU activated NF-E2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor α (PPARα), PPARγ and hemeoxygenase-1 (HO-1) and promoted the phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPKα), AMPKβ, acetyl-CoA carboxylase (ACC) and protein kinase B (AKT). In conclusion, AU performed the function of hypolipidaemic by its obvious anti-inflammation and antioxidant activity, which may become a kind of new drug targeting at NAFLD.

• Authors: Bingyu Shen, Chenxu Zhao, Yue Wang, Yi Peng, Jiaqi Cheng, Zheng Li, Lin Wu, Meiyu Jin, Haihua Feng
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 23 Issue 6 Pg. 4063-4075 (06 2019) ISSN: 1582-4934 [Electronic] England
• PMID: 30950217 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• Iridoid Glucosides
• Lipids
• Membrane Proteins
• NF-E2-Related Factor 2
• Nfe2l2 protein, mouse
• Triglycerides
• aucubin
• Cholesterol
• Heme Oxygenase-1
• Hmox1 protein, mouse
• AMP-Activated Protein Kinases

Topics

• 3T3-L1 Cells
• AMP-Activated Protein Kinases (metabolism)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (pharmacology)
• Cell Line
• Cholesterol (metabolism)
• Heme Oxygenase-1 (metabolism)
• Iridoid Glucosides (pharmacology)
• Lipid Metabolism (drug effects)
• Lipids
• Liver (drug effects, metabolism)
• Male
• Membrane Proteins (metabolism)
• Mice
• Mice, Inbred C57BL
• NF-E2-Related Factor 2 (metabolism)
• Oxidative Stress (drug effects)
• Signal Transduction (drug effects)
• Triglycerides (metabolism)