Lenthionine, a key flavour compound of shiitake mushrooms, prevents platelet aggregation by inhibiting αIIbβ3 activation

Cardiovascular diseases, which are frequently associated with thrombosis and platelet aggregation, are a significant global health concern. The inhibition of platelet aggregation is a crucial strategy for the prevention of thrombotic disorders. Our previous studies have demonstrated that lenthionine, a cyclic polysulphur compound derived from shiitake mushrooms, possesses platelet anti-aggregatory properties. However, the underlying mechanism of action remains unclear. This study aimed to elucidate the inhibitory effects of lenthionine on platelet aggregation and αIIbβ3 activation. Lenthionine inhibits platelet aggregation induced by various types of agonists. Flow cytometry and scanning electron microscopy revealed that lenthionine suppresses platelet activation and morphological changes. Moreover, lenthionine did not affect the phosphorylation/dephosphorylation of myosin light chain (MLC), cofilin, and talin, but significantly inhibited the dephosphorylation of α-actinin. Our findings suggest that lenthionine may inhibit αIIbβ3 activation by potentially inhibiting the activity of protein disulfide isomerase (PDI), which is crucial for αIIbβ3 activation.