Single-cell RNA sequencing reveals cellular dynamics and therapeutic effects of astragaloside IV in slow transit constipation.
Biomol Biomed
; 24(4): 871-887, 2024 Jan 29.
Article
em En
| MEDLINE
| ID: mdl-38289380
ABSTRACT
The cellular characteristics of intestinal cells involved in the therapeutic effects of astragaloside IV (AS-IV) for treating slow transit constipation (STC) remain unclear. This study aimed to determine the dynamics of colon tissue cells in the STC model and investigate the effects of AS-IV treatment by single-cell RNA sequencing (scRNA-seq). STC mouse models were developed using loperamide, with subsequent treatment using AS-IV. Colon tissues and feces were collected for scRNA-seq and targeted short-chain fatty acid quantification. We integrated scRNA-seq data with network pharmacology to analyze the effect of AS-IV on constipation. AS-IV showed improvement in defecation for STC mice induced by loperamide. Notably, in STC mice, epithelial cells, T cells, B cells, and fibroblasts demonstrated alterations in cell proportions and aberrant functions, which AS-IV partially rectified. AS-IV has the potential to modulate the metabolic pathway of epithelial cells through its interaction with peroxisome proliferator-activated receptor gamma (PPARγ). AS-IV reinstated fecal butyrate levels and improved energy metabolism in epithelial cells. The proportion of naïve CD4+T cells is elevated in STC, and the differentiation of these cells into regulatory T cells (Treg) is regulated by B cells and fibroblasts through the interaction of ligand-receptor pairs. AS-IV treatment can partially alleviate this trend. The status of fibroblasts in STC undergoes alterations, and the FB_C4_Adamdec1 subset, associated with angiogenesis and the Wingless-related integration (Wnt) pathway, emerges. Our comprehensive analysis identifies perturbations of epithelial cells and tissue microenvironment cells in STC and elucidates mechanisms underlying the therapeutic efficacy of AS-IV.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Saponinas
/
Triterpenos
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Constipação Intestinal
/
Análise de Célula Única
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Biomol Biomed
Ano de publicação:
2024
Tipo de documento:
Article