Previous studies found that the
collagen hydrolysates of fish skin have antiplatelet activity, but this component remained unknown. In this study, eleven
peptides were isolated and identified in the absorbates of
Alcalase-hydrolysates and Protamex®-hydrolysates of skin
collagen of H. Molitrix by reverse-phase C18 column and HPLC-MS/MS. Nine of them contained a
Pro-Gly (PG) or
Hyp-Gly (OG) sequence and significantly inhibited
ADP-induced platelet aggregation in vitro, which suggested that the PG(OG) sequence is the core sequence of
collagen peptides with antiplatelet activity. Among them, OGSA has the strongest inhibiting activities against
ADP-induced platelet aggregation in vitro (IC50 = 0.63 mM), and OGSA inhibited the
thrombus formation in rats at a dose of 200 μM/kg.bw with no risk of
bleeding. The molecular docking results implied that the OG-containing
peptides might target the P2Y12 receptor and form hydrogen bonds with the key sites Cys97, Ser101, and Lys179. As the sequence PG(OG) is abundant in the
collagen amino acid sequence of H. Molitrix, the
collagen hydrolysates of H. Molitrix might have great potential for being developed as dietary supplements to prevent
cardiovascular diseases in the future.