Tetramethylpyrazine alleviates diabetes-induced high platelet response and endothelial adhesion via inhibiting NLRP3 inflammasome activation
| Autor: | Hanyu Chen, Chao Zhang, Yejin Zhu, Xiao Zheng, Xiaohu Chen, Zhe Yin, Huaqin Tong, Tong Sun, Xiang Wu, Haowen Zhang, Manlu Fan, Weixin Sun |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Blood Platelets
Inflammasomes Pharmaceutical Science NLR Proteins Pharmacology Umbilical vein Endothelial activation chemistry.chemical_compound NLR Family Pyrin Domain-Containing 3 Protein Drug Discovery Human Umbilical Vein Endothelial Cells medicine Animals Humans Tetramethylpyrazine Platelet integumentary system Cell adhesion molecule Inflammasome Adhesion Streptozotocin Rats Diabetes Mellitus Type 2 Complementary and alternative medicine chemistry Pyrazines Molecular Medicine medicine.drug |
| Zdroj: | Phytomedicine. 96:153860 |
| ISSN: | 0944-7113 |
| DOI: | 10.1016/j.phymed.2021.153860 |
| Popis: | Background The inflammatory state of diabetes promotes high platelet response and endothelial adhesion, which are the main risk factors for cardiovascular events. Tetramethylpyrazine (TMP) is an amide alkaloid isolated from the traditional Chinese medicine Rhizoma Ligustici Chuanxiong, which has been widely used in the clinical treatment of ischemic cardiovascular disease. Purpose This study aimed to investigate whether TMP could alleviate diabetes-induced high platelet response and endothelial adhesion and the underlying mechanisms. Methods Type 2 diabetes mellitus (T2DM) rat model was established by high-fat feeding combined with low dose of streptozotocin. Rats in the TMP treatment group were administered with TMP (100 or 200 mg/kg) for 21 days. Cultured human umbilical vein endothelial cells (HUVECs) were stimulated with glucose (5.5 mM) to induce endothelial activation. The NOD-like receptor protein 3 (NLRP3) over- and low-expressing cell models were established via transfection of NLRP3 lentivirus plasmid into HUVECs. INF39 (25 mg/kg), a chemical inhibitor of NLRP3 inflammasome, was used to explore the role of NLRP3 in T2DM associated high platelet response and endothelial adhesion. Results TMP effectively improved the prothrombotic phenotypes and inhibited the expression of vascular inflammatory factors and adhesion molecules in T2DM rats. TMP inhibited NLRP3 inflammasome and reduced the adhesion of HUVECs to platelets and monocytes in vitro. Over-expression of NLRP3 blocked the effect of TMP on HUVECs activation and adhesion, while TMP had no effect on NLRP3 low-expressing HUVECs. The NLRP3 inhibitor INF39 produced similar effects of TMP on diabetes-induced high platelet response, endothelial adhesion and vascular inflammation. Conclusion TMP ameliorates diabetes-induced high platelet response and endothelial adhesion via inhibiting NLRP3 inflammasome activation in T2DM rats, which provide a new basis for the clinical prevention and treatment of diabetes-associated cardiovascular events. |
| Databáze: | OpenAIRE |
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