(-)-Syringaresinol attenuates ulcerative colitis by improving intestinal epithelial barrier function and inhibiting inflammatory responses

Yunhe Liu; Junzhe Wu; Luying Tan; Zhuoqiao Li; Peng Gao; Shanmei He; Qianyun Wang; Daohao Tang; Cuizhu Wang; Fang Wang; Pingya Li; Jinping Liu

doi:10.1016/j.phymed.2023.155292

(-)-Syringaresinol attenuates ulcerative colitis by improving intestinal epithelial barrier function and inhibiting inflammatory responses

Phytomedicine. 2024 Feb:124:155292. doi: 10.1016/j.phymed.2023.155292. Epub 2023 Dec 23.

Authors

Yunhe Liu¹, Junzhe Wu¹, Luying Tan¹, Zhuoqiao Li¹, Peng Gao¹, Shanmei He¹, Qianyun Wang¹, Daohao Tang¹, Cuizhu Wang², Fang Wang³, Pingya Li², Jinping Liu⁴

Affiliations

¹ School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130021, China.
² School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130021, China; Research Center of Natural Drugs, Jilin University, Changchun 130021, China.
³ College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
⁴ School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130021, China; Research Center of Natural Drugs, Jilin University, Changchun 130021, China. Electronic address: liujp@jlu.edu.cn.

PMID: 38190784
DOI: 10.1016/j.phymed.2023.155292

Abstract

Background: (-)-Syringaresinol (SYR), a natural lignan with significant antioxidant and anti-inflammatory activities, possesses various pharmacological benefits including cardio-protective, antibacterial, anticancer, and anti-aging effects. It was shown that the effectiveness of (+)-syringaresinol diglucoside on the ulcerative colitis (UC) was attributed to the active metabolite (+)-syringaresinol (the enantiomor of SYR). However, the efficacy of SYR against UC remains unclear, and the associated molecular mechanism has not been revealed yet PURPOSE: This study aimed to assess the protective effect of SYR in UC and its underlying mechanism STUDY DESIGN AND METHODS: We examined SYR's protective impact on the intestinal epithelial barrier and its ability to inhibit inflammatory responses in both a lipopolysaccharide (LPS)-induced Caco-2 cell model and a dextran sodium sulfate (DSS)-induced UC mouse model. We also explored the potential signaling pathways regulated by SYR using transcriptome analysis and western blot assay RESULTS: In Caco-2 cells, SYR significantly increased trans-epithelial electrical resistance, reduced tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interferon-γ (IFN-γ), and cyclooxygenase-2 (COX-2) levels, and enhanced cellular tight junction protein expression and distribution. In mice with UC, oral treatment with SYR (10, 20, 40 mg·kg^-1) dose-dependently increased body weight, colon length, and expression of tight junction proteins, decreased disease activity index score, spleen coefficient, cytokine serum levels, bacterial translocation, and intestinal damage, and also preserved the ultrastructure of colonic mucosal cells. Transcriptomics indicated that the anti-UC effect of SYR is mediated via the PI3K-Akt/MAPK/Wnt signaling pathway.

Conclusion: In summary, SYR effectively mitigated the development of UC by enhancing the intestinal epithelial barrier function and attenuating the inflammatory response. The plant-derived product SYR might be a potentially effective therapeutical agent against UC.

Keywords: (–)-Syringaresinol; Inflammation; Intestinal epithelial barrier; PI3K-Akt/MAPK/Wnt signaling pathway; Transcriptomics; Ulcerative colitis.

MeSH terms

Animals
Caco-2 Cells
Colitis* / chemically induced
Colitis, Ulcerative* / chemically induced
Colitis, Ulcerative* / drug therapy
Colitis, Ulcerative* / metabolism
Colon / pathology
Dextran Sulfate / adverse effects
Disease Models, Animal
Furans*
Humans
Intestinal Mucosa / metabolism
Lignans* / pharmacology
Lignans* / therapeutic use
Mice
Mice, Inbred C57BL
Phosphatidylinositol 3-Kinases / metabolism

Substances

syringaresinol
Phosphatidylinositol 3-Kinases
Lignans
Dextran Sulfate
Furans