Liu Siyuan, Wang Huaxiang, Wang Min, Wang Zhihui, Li Na, Si Jianyong, Ye Jingxue
Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China.
State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Beijing 100193, China.
Curr Issues Mol Biol. 2025 Jul 1;47(7):503. doi: 10.3390/cimb47070503.
G. Don is valued for its edible and medicinal qualities. It has been reported that has the potential to inhibit platelet activation, but its mechanism of action is unknown, which needs to be further explored. This study investigates the anti-myocardial ischemia-reperfusion (I/R) injury potential of from the perspective of platelet activation, focusing on its chemical composition and underlying mechanisms of action. A combination of transcriptome sequencing, molecular docking, and experimental validation was employed in our study. The antiplatelet active fraction MT-95ET of was screened by the ADP-induced platelet aggregation model in vitro. In vivo experiments demonstrated that MT-95ET can reduce the myocardial injury of I/R rats and inhibit I/R-induced platelet activation, adhesion, and aggregation. UHPLC-Q-Orbitrap-MS/MS was used to identify 13 compounds from MT-95ET. Transcriptome sequencing and molecular docking identified aerobic glycolysis key checkpoints PDK1 and PKM2 as key targets, with Sarsasapogenin and Hecogenin exhibiting strong binding affinities to these proteins. Western blot analysis further validated that MT-95ET downregulated PKM2 and PDK1, indicating a possible mechanism for its antiplatelet effects and anti-myocardial I/R injury.
G. Don因其食用和药用价值而受到重视。据报道，它具有抑制血小板活化的潜力，但其作用机制尚不清楚，需要进一步探索。本研究从血小板活化的角度研究了其抗心肌缺血再灌注（I/R）损伤的潜力，重点关注其化学成分和潜在作用机制。我们的研究采用了转录组测序、分子对接和实验验证相结合的方法。通过体外ADP诱导的血小板聚集模型筛选出其抗血小板活性组分MT-95ET。体内实验表明，MT-95ET可减轻I/R大鼠的心肌损伤，并抑制I/R诱导的血小板活化、黏附和聚集。采用UHPLC-Q-Orbitrap-MS/MS从MT-95ET中鉴定出13种化合物。转录组测序和分子对接确定有氧糖酵解关键检查点PDK1和PKM2为关键靶点，知母皂苷元（Sarsasapogenin）和海柯皂苷元（Hecogenin）对这些蛋白表现出较强的结合亲和力。蛋白质免疫印迹分析进一步验证了MT-95ET下调了PKM2和PDK1，这表明了其抗血小板作用和抗心肌I/R损伤的可能机制。
