Curcumin and Curcuma longa L. extract ameliorate lipid accumulation through the regulation of the endoplasmic reticulum redox and ER stress

Hwa-Young Lee,Seung-Wook Kim,Geum-Hwa Lee,Min-Kyung Choi,Han-Wool Chung,Yong-Chul Lee,Hyung-Ryong Kim,Ho Jeong Kwon,Han-Jung Chae

doi:10.1038/s41598-017-06872-y

Hwa-Young Lee, Seung-Wook Kim + Show 7 more

Open Access

https://doi.org/10.1038/s41598-017-06872-y

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Abstract

For this study, we examined the effects of curcumin against acute and chronic stress, paying specific attention to ROS. We also aimed to clarify the differences between acute and chronic stress conditions. We investigated the effects of curcumin against acute stress (once/1 day CCl4 treatment) and chronic-stress (every other day/4week CCl4 treatment). Compared with acute stress, in which the antioxidant system functioned properly and aspartate transaminase (AST) and ROS production increased, chronic stress increased AST, alanine aminotransferase (ALT), hepatic enzymes, and ROS more significantly, and the antioxidant system became impaired. We also found that ER-originated ROS accumulated in the chronic model, another difference between the two conditions. ER stress was induced consistently, and oxidative intra-ER protein folding status, representatively PDI, was impaired, especially in chronic stress. The PDI-associated client protein hepatic apoB accumulated with the PDI-binding status in chronic stress, and curcumin recovered the altered ER folding status, regulating ER stress and the resultant hepatic dyslipidemia. Throughout this study, curcumin and curcumin-rich Curcuma longa L. extract promoted recovery from CCl4-induced hepatic toxicity in both stress conditions. For both stress-associated hepatic dyslipidemia, curcumin and Curcuma longa L. extract might be recommendable to recover liver activity.

Highlights

Humans can be transiently or chronically exposed to environmental contaminants and pollutants
For the chronic model (0.1 mL/100 g, CCl4 every other day for 4 weeks), curcumin or Curcuma longa L. extract was given each day for 3 days before CCl4 treatment and every day during the 4-week stress period
We examined the difference between acute and chronic stress in terms of reactive oxygen species (ROS), along with the effects of curcumin and Curcuma longa L. extract against acute and chronic stress

Summary

Introduction

Humans can be transiently or chronically exposed to environmental contaminants and pollutants. Toxins from transient exposure are eliminated through liver metabolism, toxins from chronic exposure tend to accumulate in the body, leading to pathological phenomena, including hepatic dyslipidemia. Distinctive features of hepatotoxicity include hepatic dysfunction with an increase in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and hepatic dyslipidemia, in which pathological reactive oxygen species (ROS) accumulation and related signaling are the likely involved mechanisms. Under severe or chronic stress, the ROS are amplified in subcellular organelles, disturbing protein folding and secretion[1, 2]. We used CCl4 in this study to model both acute and chronic hepatotoxicity and lipid dyslipidemia. We studied the effects of both curcumin and curcumin-rich Curcuma longa L. extracts in CCl4 models to determine their therapeutic potential against hepatotoxicity and hepatic dyslipidemia and their mechanism of action, with a particular focus on ER redox imbalance

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