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Isosteviol Sodium Ameliorates Dextran Sodium Sulfate-Induced Chronic Colitis through the Regulation of Metabolic Profiling, Macrophage Polarization, and NF-κB Pathway.

Abstract
Inflammatory bowel diseases (IBDs) constitute a group of chronic intestinal conditions prominently featuring deranged metabolism. Effective pharmacological treatments for IBDs are lacking. Isosteviol sodium (STV-Na) exhibits anti-inflammatory activity and may offer therapeutic benefits in chronic colitis. However, the associated mechanism remains unclear. This study is aimed at exploring the therapeutic effects of STV-Na against chronic colitis in terms of metabolic reprogramming and macrophage polarization. Results show that STV-Na attenuated weight loss and colonic pathological damage and restored the hematological and biochemical parameters in chronic colitis mice models. STV-Na also restored intestinal permeability by increasing the goblet cell numbers, which was accompanied by lowered plasma lipopolysaccharide and diamine oxidase levels. Metabolomic analysis highlighted 102 candidate biomarkers and 5 vital pathways that may be crucial in the potential pharmacological mechanism of STV-Na in regulating intestinal inflammation and oxidative stress. These pathways were glycerophospholipid metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, the pentose phosphate pathway, and phosphonate and phosphinate metabolism. Furthermore, STV-Na significantly decreased M1 macrophage polarization in the spleen and colon. The mRNA and protein levels of IL-1β, TNF-α, and NF-κB/p65 in colonic tissue from the colitis mice were decreased after the STV-Na treatment. Overall, STV-Na could alleviate chronic colitis by suppressing oxidative stress and inflammation levels, reprogramming the metabolic profile, inhibiting macrophage polarization, and suppressing the NF-κB/p65 signaling pathway. STV-Na remains a promising candidate drug for treating IBDs.
AuthorsShanping Wang, Jiandong Huang, Keai Sinn Tan, Liangjun Deng, Fei Liu, Wen Tan
JournalOxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2022 Pg. 4636618 ( 2022) ISSN: 1942-0994 [Electronic] United States
PMID35126813 (Publication Type: Journal Article)
CopyrightCopyright © 2022 Shanping Wang et al.
Chemical References
  • Diterpenes, Kaurane
  • Glycerophospholipids
  • Interleukin-1beta
  • Lipopolysaccharides
  • Transcription Factor RelA
  • isosteviol
  • Phenylalanine
  • Dextran Sulfate
Topics
  • Animals
  • Chronic Disease
  • Colitis (chemically induced, drug therapy, pathology)
  • Colon (drug effects, metabolism, pathology)
  • Dextran Sulfate (toxicity)
  • Diterpenes, Kaurane (pharmacology, therapeutic use)
  • Glycerophospholipids (metabolism)
  • Interleukin-1beta (blood, genetics, metabolism)
  • Lipopolysaccharides (pharmacology)
  • Macrophage Activation (drug effects)
  • Macrophages (cytology, metabolism)
  • Male
  • Metabolome (drug effects)
  • Metabolomics
  • Mice
  • Mice, Inbred C57BL
  • Pentose Phosphate Pathway
  • Phenylalanine (metabolism)
  • Signal Transduction (drug effects)
  • Transcription Factor RelA (genetics, metabolism)

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