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Water-soluble polysaccharides from citri reticulatae pericarpium alleviates LCWE-induced endothelial dysfunction by targeting TLR2-mediated NF-κB-NLRP3 pathway.

Wen Xiao,Su Dong,Yue Xuan,Xiao-Jie Huang,Jing-Rui Feng,Hongjing You,Yang Chen

Published 2025 in International Journal of Biological Macromolecules

ABSTRACT

Existing studies lack systematic investigation of the polysaccharide components in Citri Reticulatae Pericarpium (CRP), despite established anti-inflammatory and cardioprotective effects of its bioactive constituents. This study isolated and characterized CRP-derived polysaccharides, focusing on CP-0's protective role against Lactobacillus casei cell wall extract (LCWE)-induced endothelial barrier dysfunction. Structural characterization identified CP-0 and CP-1 as novel triple-helical heteropolysaccharides (MW 81,404 and 83,540 Da; glucose, ribose, mannose). Following isolation and physicochemical screening, CP-0 exhibited low cytotoxicity and high anti-inflammatory activity. Mechanistic analyses revealed that CP-0 attenuated LCWE-induced endothelial injury by reducing inflammatory infiltration, IL-1β levels, and adhesion molecules (VCAM-1/ICAM-1) while upregulating tight junction proteins ZO-1/2 in mouse microvascular endothelial cells (MVECs). CP-0 suppressed NLRP3 inflammasome activation via decreased colocalization of NLRP3/Caspase-1/ASC, and competitive binding assays confirmed its interaction with TLR2, which blocked NF-κB nuclear translocation. By targeting TLR2-mediated signaling pathways, CP-0 effectively mitigated LCWE-induced coronary arteritis in vitro, demonstrating potential as a therapeutic candidate for cardiovascular diseases through early-stage anti-inflammatory intervention.

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