Anticoagulant Activity of Low-Molecular Weight Compounds from Heterometrus laoticus Scorpion Venom

Abstract

Scorpion venoms are complex polypeptide mixtures, the ion channel blockers and antimicrobial peptides being the best studied components. The coagulopathic properties of scorpion venoms are poorly studied and the data about substances exhibiting these properties are very limited. During research on the Heterometrus laoticus scorpion venom, we have isolated low-molecular compounds with anticoagulant activity. Determination of their structure has shown that one of them is adenosine, and two others are dipeptides LeuTrp and IleTrp. The anticoagulant properties of adenosine, an inhibitor of platelet aggregation, are well known, but its presence in scorpion venom is shown for the first time. The dipeptides did not influence the coagulation time in standard plasma coagulation tests. However, similarly to adenosine, both peptides strongly prolonged the bleeding time from mouse tail and in vitro clot formation in whole blood. The dipeptides inhibited the secondary phase in platelet aggregation induced by ADP, and IleTrp decreased an initial rate of platelet aggregation induced by collagen. This suggests that their anticoagulant effects may be realized through the deterioration of platelet function. The ability of short peptides from venom to slow down blood coagulation and their presence in scorpion venom are established for the first time. Further studies are needed to elucidate the precise molecular mechanism of dipeptide anticoagulant activity.

Nanoencapsulation Enhances Anticoagulant Activity of Adenosine and Dipeptide IleTrp

“…The bleeding time was determined within two hours after injection and the data obtained are shown in Figure 7. As it was shown earlier [23], at all times tested, the injection of Ado and IW resulted in substantial increase in the bleeding time. Injection of heparin led to an increase in bleeding time only for the first 10 min.…”

“…Determination of anticoagulant activity was done as described [23]. In brief, the solution containing encapsulated anticoagulant in 0.9% NaCl was injected in lateral veins of mouse tails at a dose of 2.48 mg/kg calculated for IW or Ado (injection volume 0.1 mL per 10 g of mouse body weight).…”

“…Sustained release of the drug from polymeric nanoparticles was observed for a greater period than after injection of enoxaparin. These results indicate prospects for the use of nanomaterials in clinical practice.Earlier in the venom of Heterometrus laoticus scorpion, the dipeptide IleTrp (IW) and adenosine (Ado), both exhibiting anticoagulant properties were found [23]. In this paper, it is reported that the encapsulation of Ado and IW in the pluronic P123-grafted heparin (Hep-P123) nanomaterials significantly enhanced their anticoagulant properties, providing sustained drug release over time.…”

“…Earlier in the venom of Heterometrus laoticus scorpion, the dipeptide IleTrp (IW) and adenosine (Ado), both exhibiting anticoagulant properties were found [23]. In this paper, it is reported that the encapsulation of Ado and IW in the pluronic P123-grafted heparin (Hep-P123) nanomaterials significantly enhanced their anticoagulant properties, providing sustained drug release over time.…”

Toxins in Drug Discovery and Pharmacology

“…Two dipeptides with anticoagulant activity have been isolated from scorpion venom [ 21 ]. This study shows for the first time the ability of short venom peptides to slow down blood coagulation.…”