Ginsenoside Mc1 improves liver steatosis and insulin resistance by attenuating ER stress

Eun Roh, Hwan Jin Hwang, Joo Won Kim, So hyeon Hong, Jung A. Kim, You Bin Lee, Kyung Mook Choi, Sei Hyun Baik, Hye Jin Yoo

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


Ethnopharmacological relevance: Ginsenoside, a major pharmacologically active ingredient in ginseng, has been known to exhibit beneficial properties such as antioxidant and anti-inflammatory effects. Ginsenoside compound Mc1 is one of the newly identified de-glycosylated ginsenosides. Endoplasmic reticulum (ER) stress has implicated in the development of non-alcoholic fatty liver disease (NAFLD) through apoptosis and lipid accumulation. Aim of the study: We aimed to examine the protective effects of Mc1 treatment on ER stress-induced cell death and impaired insulin signaling in HepG2 human hepatoblastoma cells and ER stress-induced liver steatosis and insulin resistance in a diet-induced obesity (DIO) mouse model. Materials and methods: HepG2 cells were treated with palmitate and Mc1 to evaluate the effects of Mc1 on ER stress-induced damage. C57BL/6 mice were fed with a high-fat diet (HFD) for 4 weeks and received an intraperitoneal injection of either vehicle or Mc1 (10 mg/kg/day). The control mice were fed with a chow diet and injected with vehicle for the same period. ER stress, cell death, and degree of steatosis were evaluated in the liver tissues of mice. The effect of Mc1 treatment on glucose metabolism was also determined. Results: Mc1 co-treatment reduced the palmitate-induced ER stress and death of HepG2 cells. The palmitate-induced insulin resistance improved after Mc1 co-treatment. Consistent with the in vitro data, chronic Mc1 supplementation reduced ER stress and apoptotic damage in the liver of obese mice. Mc1 treatment ameliorated glucose intolerance and insulin resistance through the suppression of c-Jun N-terminal kinase (JNK) phosphorylation. In addition, Mc1 treatment reduced obesity-induced lipogenesis and prevented fat accumulation in the liver of DIO mice. Conclusions: Mc1 exerted protective effects against ER stress-induced apoptotic damage, insulin resistance and lipogenesis in palmitate-treated hepatocytes and in the liver of DIO mice. Therefore, Mc1 supplementation could be a potential therapeutic strategy to prevent NAFLD in patients with obesity and insulin resistance.

Original languageEnglish
Article number112927
JournalJournal of Ethnopharmacology
Publication statusPublished - 2020 Sept 15

Bibliographical note

Funding Information:
This work was supported by grants from the National Research Foundation of Korea (NRF) funded by the Ministry of Education ( 2018R1D1A1B07047587 , 2018R1D1A1B07050991 ) and by the Korea University Guro Hospital Grant ( O1903911 ). The funders had no role in the study design, data collection, analysis, and interpretation, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2020


  • ER stress
  • Ginsenoside Mc1
  • Hepatic steatosis
  • Insulin resistance
  • Obesity

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery


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