Protective Effect of Gomisin N against Endoplasmic Reticulum Stress-Induced Hepatic Steatosis

• Published in: Biological & pharmaceutical bulletin Vol. 39; no. 5; pp. 832 - 838
• Main Authors: Jang, Min-Kyung, Yun, Ye-Rang, Kim, Seon Hoo, Kim, Ji Ha, Jung, Myeong Ho
• Format: Journal Article
• Language: English; Japanese
• Published: Japan The Pharmaceutical Society of Japan 01.05.2016; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Acetyl-CoA Carboxylase - genetics; Animals; Cyclooctanes - pharmacology; Cyclooctanes - therapeutic use; Cytokines - genetics; endoplasmic reticulum (ER) stress; Endoplasmic Reticulum Stress - drug effects; Fatty Acid Synthase, Type I - genetics; Fatty Liver - chemically induced; Fatty Liver - drug therapy; Fatty Liver - metabolism; Glycerol-3-Phosphate O-Acyltransferase - genetics; gomisin N; Heat-Shock Proteins - metabolism; Hep G2 Cells; hepatic steatosis; Humans; inflammation; Lignans - pharmacology; Lignans - therapeutic use; lipogenesis; Liver - drug effects; Liver - metabolism; Mice, Inbred C57BL; Palmitic Acid; Polycyclic Compounds - pharmacology; Polycyclic Compounds - therapeutic use; Protective Agents - pharmacology; Protective Agents - therapeutic use; Transcription Factor CHOP - metabolism; Triglycerides - metabolism; Tunicamycin; X-Box Binding Protein 1 - metabolism
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b15-01020

Gomisin N is a physiological substance derived from Schisandra chinensis. In the present study, the in vitro and in vivo effects of gomisin N on endoplasmic reticulum (ER) stress and hepatic steatosis were investigated. We quantified the expression of markers of ER stress, including glucose regulated protein 78 (GRP78), CCAAT/enhancer binding protein (C/EBP) homolog protein (CHOP), and X-box-binding protein-1 (XBP-1), and triglyceride (TG) accumulation, in HepG2 cells treated with tunicamycin or palmitate. Tunicamycin treatment in HepG2 cells induced expression of markers of ER stress and increased TG levels; Gomisin N reversed these effects, reducing the expression of markers of ER stress and TG levels. Similar effects were seen following palmitate pretreatment of HepG2 cells. The inhibitory effects of gomisin N were further confirmed in mice injected with tunicamycin. Gomisin N reduced expression of markers of ER stress and decreased TG levels in mouse liver after tunicamycin injection. Furthermore, gomisin N decreased expression of inflammatory and lipogenic genes in palmitate-incubated HepG2 cells. These results suggest that gomisin N inhibits ER stress and ameliorates hepatic steatosis induced by ER stress.