J Nutr Health.  2020 Dec;53(6):583-595. 10.4163/jnh.2020.53.6.583.

Inhibitory effects of Sargassum horneri extract against endoplasmic reticulum stress in HepG2 cells

• Park S
• Thomas SS
• Cha YS
• Kim KA

• KMID: 2510206
• DOI: http://doi.org/10.4163/jnh.2020.53.6.583

Abstract

Purpose
This study examined the effects of Sargassum horneri extracts on palmitic acid (PA)-induced endoplasmic reticulum (ER) stress in HepG2 cells.
Methods
HepG2 cells were treated with varying concentrations of S. horneri extract or PA, and the cell viability was measured by water soluble tetrazolium salts analysis. The effective induction of ER stress and the effects of S. horneri were investigated through an examination of the ER stress-related genes, such as activating transcription factor 4 (ATF4), X-box binding protein (XBP1s), C/EBP homologous protein (CHOP), and 78-kDa glucose-regulated protein (GRP78) by quantitative reverse transcription polymerase chain reaction. The expression and activation levels of unfolded protein response (UPR) associated proteins, such as inositolrequiring enzyme-1α (IRE1α), eukaryotic translation initiation factor 2 alpha submit (eIF2α), and CHOP were examined by western blot analysis.
Results
The treatment with PA increased the expression of UPR associated genes significantly and induced ER stress in a 12-hour treatment. Subsequent treatment with S. horneri reduced mRNA expression of ATF4, GRP78, and XBP1s. In addition, the protein levels of phosphate (p)-IRE1α, p-elF2α, and CHOP were also reduced by a treatment with S. horneri. An analysis of sirtuin (SIRT) mRNA expression in the S. horneri and PA-treated HepG2 cells showed that S. horneri increased the levels of SIRT2, SIRT6, and SIRT7, which indicates a possible role in reducing the expression of ER stress-related genes.
Conclusion
These data indicate thatS. horneri can exert an inhibitory effect on ER stress caused by PA and highlight its potential as an agent for managing various ER stress-related diseases.

Keyword

Sargassum horneri; palmitic acid; endoplasmic reticulum stress; sirtuin