Journal Article Epublish 1 citation
PubMed: 40137296 DOI: 10.3390/md23030110
Fucosylated Glycosaminoglycan Oligosaccharide HS14, Derived from Sea Cucumbers, Is a Novel Inhibitor of Platelet Toll-like Receptor 2.
Mar Drugs 23(3)
Authors: Huifang Sun, Guangyu Zhu, Sujuan Li, Pengfei Li, Jiali Zhang, Ronghua Yin, Lin Yuan, Na Gao, Jinhua Zhao
Affiliations
- School of Chemistry and Materials Science, South-Central Minzu University, Wuhan 430074, China.
- College of Life Sciences, South-Central Minzu University, Wuhan 430074, China.
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.
- School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan 430074, China.
Abstract
(1) Background: Toll-like receptor 2 (TLR2) on platelets is increasingly recognized as a pivotal mediator in infection-induced platelet activation and aggregation, contributing to both inflammatory and thrombotic diseases. Targeting TLR2 on platelets offers a promising therapeutic strategy for inflammatory and thrombotic-related disorders. However, inhibitors targeting platelet TLR2 have not yet been reported. (2) Methods: Platelet aggregation was assessed using a light transmission aggregometer. Platelet activation was evaluated by measuring the release of P-selectin and von Willebrand factor (vWF) via ELISA. Intracellular Ca mobilization was quantified using Fluo 3-AM fluorescence, recorded by flow cytometry. Static platelet adhesion was visualized under a microscope, and the formation of platelet-granulocyte aggregates in human whole blood was analyzed by flow cytometry. (3) Results: Fucosylated glycosaminoglycan (FG) tetradecasaccharide HS14 inhibited the activation and aggregation of human platelets induced by the synthetic bacterial lipopeptide Pam3CSK4 in a concentration-dependent manner. This inhibitory effect gives rise to significant anti-inflammatory and anti-thrombotic activities, as evidenced by reduced platelet adhesion and decreased platelet-granulocyte aggregates formation in human whole blood. (4) Conclusions: This study is the first to identify FG oligosaccharide HS14 as a promising inhibitor of platelet TLR2/TLR1, demonstrating significant therapeutic potential for inflammatory and thrombotic-related diseases.
MeSH
Toll-Like Receptors, Tissue Adhesions, Flow Cytometry, Oligosaccharides, Blood, Toll-Like Receptor 2, Pharmaceutical Preparations, Glycosaminoglycans, Granulocytes, Platelet Aggregation, Therapeutics, Blood Platelets, Platelet Activation