Sacran, a sulfated polysaccharide, suppresses the absorption of lipids and modulates the intestinal flora in non-alcoholic steatohepatitis model rats.

Abstract

AIMS:

The objective of this study was to investigate the effects of administering sacran, a sulfated polysaccharide, on liver biology, gut microbiota, oxidative stress, and inflammation on stroke-prone spontaneously hypertensive (SHRSP5/Dmcr) rats that develop fibrotic steatohepatitis with histological similarities to that of non-alcoholic steatohepatitis (NASH).

MAIN METHODS:

Four groups of 8-week-old SHRSP5/Dmcr rats were fed a high fat-cholesterol (HFC) diet for 4 and 8 weeks and administered either sacran (80 mg/kg/day) or a non-treatment, respectively. Liver function was evaluated by biochemical and histopathological analyses. Hepatic inflammatory markers were measured using mRNA expression. Fecal microbial profiles were determined via 16S rRNA sequencing. A triglyceride (TG) absorption test was administered to the 8-week-old Sprague-Dawley (SD) rats.

KEY FINDING:

Sacran administration was observed to decrease the extent of oxidative stress and hepatic biochemical parameters in serum and hepatic injury with the levels of transforming growth factor-beta (TGF-β1) and tumor necrosis factor-alpha (TNF-α), being increased compared to those of the non-treatment group. At the genus level, sacran administration caused a significant decrease in the harmful Prevotella genus, and a significant increase in the useful Blautia genus was observed. Sacran administration also decreased the serum TG increase that was induced by administering corn oil to the SD rats.

SIGNIFICANCE:

We conclude that sacran administration has the potential to reduce the absorption of lipids into blood and to improve several gut microbiotas, in the gastrointestinal tract, thereby inhibiting the subsequent development of oxidative stress and hepatic markers in the systematic circulation on NASH.

• Authors: Miwa Goto, Kazuo Azuma, Hidetoshi Arima, Shinichiro Kaneko, Taishi Higashi, Keiichi Motoyama, Akihiro Michihara, Takae Shimizu, Daisuke Kadowaki, Toru Maruyama, Masaki Otagiri, Daisuke Iohara, Fumitoshi Hirayama, Makoto Anraku
• Journal: Life sciences (Life Sci) Vol. 268 Pg. 118991 (Mar 01 2021) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 33417955 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Lipids
• Polysaccharides
• sacran

Topics

• Animals
• Blood Pressure (drug effects, physiology)
• Body Weight (drug effects)
• Diet, High-Fat (adverse effects)
• Disease Models, Animal
• Gastrointestinal Microbiome (drug effects, physiology)
• Lipid Metabolism (drug effects)
• Lipids (blood, pharmacokinetics)
• Male
• Non-alcoholic Fatty Liver Disease (drug therapy, metabolism, microbiology)
• Polysaccharides (pharmacology)
• Rats, Inbred SHR
• Rats, Sprague-Dawley