Fucosylated Glycosaminoglycan Oligosaccharide HS14, Derived from Sea Cucumbers, Is a Novel Inhibitor of Platelet Toll-like Receptor 2
(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 infla...
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2025-03-01
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| author | Huifang Sun Guangyu Zhu Sujuan Li Pengfei Li Jiali Zhang Ronghua Yin Lin Yuan Na Gao Jinhua Zhao |
| author_facet | Huifang Sun Guangyu Zhu Sujuan Li Pengfei Li Jiali Zhang Ronghua Yin Lin Yuan Na Gao Jinhua Zhao |
| author_sort | Huifang Sun |
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| description | (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<sup>2+</sup> 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. |
| format | Article |
| id | doaj-art-9cefa6be22ea443f88858879499767a3 |
| institution | OA Journals |
| issn | 1660-3397 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
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| series | Marine Drugs |
| spelling | doaj-art-9cefa6be22ea443f88858879499767a32025-08-20T02:11:11ZengMDPI AGMarine Drugs1660-33972025-03-0123311010.3390/md23030110Fucosylated Glycosaminoglycan Oligosaccharide HS14, Derived from Sea Cucumbers, Is a Novel Inhibitor of Platelet Toll-like Receptor 2Huifang Sun0Guangyu Zhu1Sujuan Li2Pengfei Li3Jiali Zhang4Ronghua Yin5Lin Yuan6Na Gao7Jinhua Zhao8School of Chemistry and Materials Science, South-Central Minzu University, Wuhan 430074, ChinaCollege of Life Sciences, South-Central Minzu University, Wuhan 430074, ChinaState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, ChinaSchool of Pharmaceutical Sciences, South-Central Minzu University, Wuhan 430074, ChinaSchool of Pharmaceutical Sciences, South-Central Minzu University, Wuhan 430074, ChinaSchool of Pharmaceutical Sciences, South-Central Minzu University, Wuhan 430074, ChinaSchool of Pharmaceutical Sciences, South-Central Minzu University, Wuhan 430074, ChinaSchool of Pharmaceutical Sciences, South-Central Minzu University, Wuhan 430074, ChinaSchool of Pharmaceutical Sciences, South-Central Minzu University, Wuhan 430074, China(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<sup>2+</sup> 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.https://www.mdpi.com/1660-3397/23/3/110toll-like receptor 2platelet activationplatelet aggregationplatelet–granulocyte aggregatesfucosylated glycosaminoglycaninflammatory diseases |
| spellingShingle | Huifang Sun Guangyu Zhu Sujuan Li Pengfei Li Jiali Zhang Ronghua Yin Lin Yuan Na Gao Jinhua Zhao Fucosylated Glycosaminoglycan Oligosaccharide HS14, Derived from Sea Cucumbers, Is a Novel Inhibitor of Platelet Toll-like Receptor 2 Marine Drugs toll-like receptor 2 platelet activation platelet aggregation platelet–granulocyte aggregates fucosylated glycosaminoglycan inflammatory diseases |
| title | Fucosylated Glycosaminoglycan Oligosaccharide HS14, Derived from Sea Cucumbers, Is a Novel Inhibitor of Platelet Toll-like Receptor 2 |
| title_full | Fucosylated Glycosaminoglycan Oligosaccharide HS14, Derived from Sea Cucumbers, Is a Novel Inhibitor of Platelet Toll-like Receptor 2 |
| title_fullStr | Fucosylated Glycosaminoglycan Oligosaccharide HS14, Derived from Sea Cucumbers, Is a Novel Inhibitor of Platelet Toll-like Receptor 2 |
| title_full_unstemmed | Fucosylated Glycosaminoglycan Oligosaccharide HS14, Derived from Sea Cucumbers, Is a Novel Inhibitor of Platelet Toll-like Receptor 2 |
| title_short | Fucosylated Glycosaminoglycan Oligosaccharide HS14, Derived from Sea Cucumbers, Is a Novel Inhibitor of Platelet Toll-like Receptor 2 |
| title_sort | fucosylated glycosaminoglycan oligosaccharide hs14 derived from sea cucumbers is a novel inhibitor of platelet toll like receptor 2 |
| topic | toll-like receptor 2 platelet activation platelet aggregation platelet–granulocyte aggregates fucosylated glycosaminoglycan inflammatory diseases |
| url | https://www.mdpi.com/1660-3397/23/3/110 |
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