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Magnesium isoglycyrrhizinate reduces hepatic lipotoxicity through regulating metabolic abnormalities

Lu, Li; Hao, Kun; Hong, Yu; Liu, Jie; Zhu, Jinwei; Jiang, Wenjiao; Zhu, Zheying; Wang, Guangji; Peng, Ying

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Li Lu

Kun Hao

Yu Hong

Jie Liu

Jinwei Zhu

Wenjiao Jiang

Associate Professor in International Pharmacy and Traditional Medicines

Guangji Wang

Ying Peng


The excessive accumulation of lipids in hepatocytes induces a type of cytotoxicity called hepatic lipotoxicity, which is a fundamental contributor to liver metabolic diseases (such as NAFLD). Magnesium isoglycyrrhizinate (MGIG), a magnesium salt of the stereoisomer of natural glycyrrhizic acid, is widely used as a safe and effective liver protectant. However, the mechanism by which MGIG protects against NAFLD remains unknown. Based on the significant correlation between NAFLD and the reprogramming of liver metabolism, we aimed to explore the beneficial effects of MGIG from a metabolic viewpoint in this paper. We treated HepaRG cells with palmitic acid (PA, a saturated fatty acid of C16:0) to induce lipotoxicity and then evaluated the antagonistic effect of MGIG on lipotoxicity by investigating the cell survival rate, DNA proliferation rate, organelle damage, and endoplasmic reticulum stress (ERS). Metabolomics, lipidomics, and isotope tracing were used to investigate changes in the metabolite profile, lipid profile, and lipid flux in HepaRG cells under different intervention conditions. The results showed that MGIG can indeed protect hepatocytes against PA-induced cytotoxicity and ERS. In response to the metabolic abnormality of lipotoxicity, MGIG curtailed the metabolic activation of lipids induced by PA. The content of total lipids and saturated lipids containing C16:0 chains increased significantly after PA stimulation and then decreased significantly or even returned to normal levels after MGIG intervention. Lipidomic data show that glycerides and glycerophospholipids were the two most affected lipids. For excessive lipid accumulation in hepatocytes, MGIG can downregulate the expression of the metabolic enzymes (GPATs and DAGTs) involved in triglyceride biosynthesis. In conclusion, MGIG has a positive regulatory effect on the metabolic disorders that occur in hepatocytes under lipotoxicity, and the main mechanisms of this effect are in lipid metabolism, including reducing the total lipid content, reducing lipid saturation, inhibiting glyceride and glycerophospholipid metabolism, and downregulating the expression of metabolic enzymes in lipid synthesis.


Lu, L., Hao, K., Hong, Y., Liu, J., Zhu, J., Jiang, W., …Peng, Y. (2021). Magnesium isoglycyrrhizinate reduces hepatic lipotoxicity through regulating metabolic abnormalities. International Journal of Molecular Sciences, 22(11), Article 5884.

Journal Article Type Article
Acceptance Date May 27, 2021
Online Publication Date May 30, 2021
Publication Date May 30, 2021
Deposit Date May 27, 2021
Publicly Available Date Jun 1, 2021
Journal International Journal of Molecular Sciences
Print ISSN 1661-6596
Electronic ISSN 1422-0067
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 22
Issue 11
Article Number 5884
Keywords Magnesium isoglycyrrhizinate; Palmitic acid; Hepatic lipotoxicity; Metabonomics; Lipidomics
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