Magnesium isoglycyrrhizinate alleviates fructose-induced liver oxidative stress and inflammatory injury through suppressing NOXs.

Abstract

Excessive fructose intake is a risk factor for liver oxidative stress injury. Magnesium isoglycyrrhizinate as a hepatoprotective agent is used to treat liver diseases in clinic. However, its antioxidant effects and the underlying potential mechanisms are still not clearly understood. In this study, magnesium isoglycyrrhizinate was found to alleviate liver oxidative stress and inflammatory injury in fructose-fed rats. Magnesium isoglycyrrhizinate suppressed hepatic reactive oxygen species overproduction (0.97 ± 0.04 a.u. versus 1.34 ± 0.07 a.u.) in fructose-fed rats by down-regulating mRNA and protein levels of nicotinamide adenine dinucleotide phosphate oxidase (NOX) 1, NOX2 and NOX4, resulting in reduction of interleukin-1β (IL-1β) levels (1.13 ± 0.09 a.u. versus 1.97 ± 0.12 a.u.). Similarly, magnesium isoglycyrrhizinate reduced reactive oxygen species overproduction (1.07 ± 0.02 a.u. versus 1.35 ± 0.06 a.u.) and IL-1β levels (1.14 ± 0.09 a.u. versus 1.66 ± 0.07 a.u.) in fructose-exposed HepG2 cells. Furthermore, data from treatment of reactive oxygen species inhibitor N-acetyl-L-cysteine or NOXs inhibitor diphenyleneiodonium in fructose-exposed HepG2 cells showed that fructose enhanced NOX1, NOX2 and NOX4 expression to increase reactive oxygen species generation, causing oxidative stress and inflammation, more importantly, these disturbances were significantly attenuated by magnesium isoglycyrrhizinate. The molecular mechanisms underpinning these effects suggest that magnesium isoglycyrrhizinate may inhibit NOX1, NOX2 and NOX4 expression to reduce reactive oxygen species generation, subsequently prevent liver oxidative stress injury under high fructose condition. Thus, the blockade of NOX1, NOX2 and NOX4 expression by magnesium isoglycyrrhizinate may be the potential therapeutic approach for improving fructose-induced liver injury in clinic.

• Authors: Yan-Zi Yang, Zhi-Hong Liu, Shan-Chun Wang, Xi-Quan Zhang, Hong-Jiang Xu, Ling Yang, Ling-Dong Kong
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 883 Pg. 173314 (Sep 15 2020) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 32619679 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• 18alpha,20beta-hydroxy-11-oxo-norolean-12-en-3beta-yl-2-O-beta-D-glucopyranurosyl-alpha-D-glucopyranosiduronate magnesium tetrahydrate
• Anti-Inflammatory Agents
• Antioxidants
• IL1B protein, rat
• Inflammation Mediators
• Interleukin-1beta
• Saponins
• Triterpenes
• Fructose
• Cybb protein, rat
• NADPH Oxidase 1
• NADPH Oxidase 2
• NADPH Oxidase 4
• NADPH Oxidases
• NOX1 protein, rat
• Nox4 protein, rat

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (pharmacology)
• Chemical and Drug Induced Liver Injury (enzymology, pathology, prevention & control)
• Disease Models, Animal
• Fructose
• Hep G2 Cells
• Humans
• Inflammation Mediators (metabolism)
• Interleukin-1beta (metabolism)
• Liver (drug effects, enzymology, pathology)
• Male
• NADPH Oxidase 1 (antagonists & inhibitors, metabolism)
• NADPH Oxidase 2 (antagonists & inhibitors, metabolism)
• NADPH Oxidase 4 (antagonists & inhibitors, metabolism)
• NADPH Oxidases (antagonists & inhibitors, metabolism)
• Oxidative Stress (drug effects)
• Rats, Sprague-Dawley
• Saponins (pharmacology)
• Signal Transduction
• Triterpenes (pharmacology)