Schisandrin B attenuates the platelet activation-thrombosis cascade through inhibition of Phosphatidylinositol 3-kinase/AKT and Extracellular signal-regulated kinase-Talin-mediated integrin αIIbβ3 signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandrin B (Sch B), a principal bioactive lignan derived from Schisandra chinensis (Turcz.) Baill. exhibits diverse pharmacological activities. This traditional Chinese medicine possesses therapeutic value for treating symptoms such as palpitations, shortness of breath, and a faint, nearly imperceptible pulse caused by deficiency of both qi and yin.

AIM OF THE STUDY: This study aimed to investigate the molecular mechanisms underlying the effects of Sch B on platelet activation and thrombosis, employing a combination of network pharmacology, molecular docking, and comprehensive in vitro and in vivo functional assays.

MATERIALS AND

METHODS

Platelet aggregation and adenosine triphosphate (ATP) release were assessed using a lumi-aggregometer. Flow cytometry was used to evaluate Sch B's effects on P-selectin expression and integrin αIIbβ3 activation. Platelet adhesion, spreading, and clot retraction assays were performed to analyze outside-in signaling. Potential targets and signaling pathways of Sch B were predicted through network pharmacology, molecular docking, and Cellular thermal shift assay (CETSA), and these predictions were further investigated using western blot analysis. In vivo, the effects of Sch B on thrombus formation were evaluated using murine models.

RESULTS

Sch B significantly suppressed platelet aggregation, granule release, adhesion, spreading, P-selectin expression, and PAC-1 binding. Western blot further analysis revealed that Sch B reduced the phosphorylation of key signaling molecules, such as Phosphatidylinositol 3-kinase (PI3K), AKT, Extracellular signal-regulated kinase (ERK), P38 mitogen-activated protein kinase (P38 MAPK), Talin1, and β3 integrin. In a mesenteric arterial thrombosis model induced by ferric chloride (FeCl3), Sch B significantly prolonged the time to stable thrombus formation. However, it did not significantly effect coagulation parameters or tail-bleeding time in mice.

CONCLUSIONS

Sch B inhibits platelet activation by interfering with the PI3K/AKT/ERK-Talin signaling pathway, thereby attenuating thrombus formation. This supports its potential as an antiplatelet agent with a favorable safety profile.