Sagittaria sagittifolia polysaccharide interferes with arachidonic acid metabolism in non-alcoholic fatty liver disease mice via Nrf2/HO-1 signaling pathway.

Abstract

BACKGROUNDS:

Non-alcoholic fatty liver disease (NAFLD) is currently one of the most common chronic liver diseases especially in developed countries. Modern research shows an obvious protective effect of Sagittaria sagittifolia L. (Alismataceae) on glucose and lipid metabolism disorders. Previous studies had reported that Sagittaria sagittifolia polysaccharide (SSP) has potent protective effects on drug-induced liver injury. Based on this, we speculated that Sagittaria sagittifolia polysaccharide also has protective effects on NAFLD and performed experiments to explore this more.

METHODS:

Outstanding protective effects of SSP against NAFLD in mice was observed with Hematoxylin and Eosin (H&E) and uranium acetate-citrate stain in our prophase research. By performing bioinformatics analysis on plasma metabolic data which is obtained from ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS), we found the regulatory mechanisms and key nodes behind the beneficial effect with IPA (Ingenuity Pathway Analysis) software. Immunohistochemical staining and Western blot were performed for further validation on expression variations of key proteins.

RESULTS:

Regulatory pathways were enriched with 33 significant differential metabolites that responded to SSP treatment in plasma, and specifically, the ones related to arachidonic acid metabolism showed high participation. Moreover, the expression patterns of upstream regulators, Nrf2 and HO-1, were found to be significantly regulated upon SSP treatment.

CONCLUSIONS:

In conclusion, our findings illustrated a novel perspective that SSP exerts preventive protection against high-fat diet-induced NAFLD by interfering with arachidonic acid metabolism via Nrf2/HO-1 signaling pathway in liver oxidative stress, providing an attractive point for the breakthrough of related natural medicine development.

• Authors: Xinqi Deng, Xiuhui Ke, Yibo Tang, Weizao Luo, Ruijuan Dong, Dongyu Ge, Li Han, Yajie Yang, Hongshuang Liu, Tuerxun Reyila, Yan Liao
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 132 Pg. 110806 (Dec 2020) ISSN: 1950-6007 [Electronic] France
• PMID: 33027743 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Membrane Proteins
• NF-E2-Related Factor 2
• Nfe2l2 protein, mouse
• Polysaccharides
• Arachidonic Acid
• Heme Oxygenase-1
• Hmox1 protein, mouse

Topics

• Animals
• Arachidonic Acid (metabolism)
• Diet, High-Fat
• Disease Models, Animal
• Heme Oxygenase-1 (metabolism)
• Male
• Membrane Proteins (metabolism)
• Mice
• Mice, Inbred ICR
• NF-E2-Related Factor 2 (metabolism)
• Non-alcoholic Fatty Liver Disease (physiopathology, prevention & control)
• Oxidative Stress (drug effects)
• Polysaccharides (isolation & purification, pharmacology)
• Sagittaria (chemistry)
• Signal Transduction (drug effects)