Life sciences · 2026
Thiamine pyrophosphate suppresses platelet activation by modulating PI3K-Akt and MAPK pathways: An integrated network pharmacology and experimental study.
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Li Qin, Yang Ruping, Wu Meng, Li Mengyao, Shen Yueyue, Chen Shuai, Yang Zhanzhan, Liu Gang
Аннотация
AIMS: Aberrant platelet activation is a major contributor to thrombotic pathologies such as atherosclerosis and acute coronary syndrome. Previous studies have suggested that supraphysiological doses of thiamine pyrophosphate (TPP), the primary active form of vitamin B1, may hold therapeutic promise for cardiovascular diseases. Here, we aimed to investigate the antithrombotic effects of TPP and elucidate its underlying mechanisms.
MATERIALS AND METHODS: The antiplatelet activity of TPP was assessed in vitro using human platelets stimulated with various agonists. Assays included aggregation, secretion, adhesion, spreading, flow cytometry, and immunoblotting. Network pharmacology and molecular docking were employed to predict targets. Complementary in vivo studies in mice evaluated effects on coagulation, tail-bleeding time, and FeCl3-induced arterial thrombosis.
KEY FINDINGS: Network pharmacology identified 177 potential targets that link TPP to thrombosis, with significant enrichment in the phosphatidylinositol 3-kinase-adenosine diphosphate (PI3K-Akt) and mitogen-activated protein kinase (MAPK) signaling pathways. In vitro, TPP effectively inhibited human platelet activation, including aggregation, integrin αIIbβ3 activation, and P-selectin expression, without affecting the basal receptor levels or cell viability. It also suppressed adhesion, spreading, calcium mobilization, and key signaling phosphorylation events. In a murine model, TPP gavage (7-day) significantly attenuated FeCl3-induced arterial thrombosis without impairing normal hemostasis.
SIGNIFICANCE: Our study demonstrated that supraphysiological TPP exerts multitargeted effects by synergistically suppressing PI3K-Akt/GSK3β and p38/ERK-MAPK axes. These findings reveal a novel biological function of TPP and suggest that this endogenous nutrient could be a promising antiplatelet drug for the prevention of thrombosis, highlighting the intersection between nutrition and cardiovascular health.
MATERIALS AND METHODS: The antiplatelet activity of TPP was assessed in vitro using human platelets stimulated with various agonists. Assays included aggregation, secretion, adhesion, spreading, flow cytometry, and immunoblotting. Network pharmacology and molecular docking were employed to predict targets. Complementary in vivo studies in mice evaluated effects on coagulation, tail-bleeding time, and FeCl3-induced arterial thrombosis.
KEY FINDINGS: Network pharmacology identified 177 potential targets that link TPP to thrombosis, with significant enrichment in the phosphatidylinositol 3-kinase-adenosine diphosphate (PI3K-Akt) and mitogen-activated protein kinase (MAPK) signaling pathways. In vitro, TPP effectively inhibited human platelet activation, including aggregation, integrin αIIbβ3 activation, and P-selectin expression, without affecting the basal receptor levels or cell viability. It also suppressed adhesion, spreading, calcium mobilization, and key signaling phosphorylation events. In a murine model, TPP gavage (7-day) significantly attenuated FeCl3-induced arterial thrombosis without impairing normal hemostasis.
SIGNIFICANCE: Our study demonstrated that supraphysiological TPP exerts multitargeted effects by synergistically suppressing PI3K-Akt/GSK3β and p38/ERK-MAPK axes. These findings reveal a novel biological function of TPP and suggest that this endogenous nutrient could be a promising antiplatelet drug for the prevention of thrombosis, highlighting the intersection between nutrition and cardiovascular health.