A novel protease-activated receptor 1 inhibitor from the leech Whitmania pigra / 中国天然药物

Whitmania pigra has been used as a traditional Chinese medicine (TCM) for promoting blood circulation, alleviating blood coagulation, activating meridians and relieving stasis for several hundred years. However, the therapeutic components of this species, especially proteins and peptides were poorly exploited. Until now only a few of them were obtained by using chromatographic isolation and purification. In recent decade, transcriptome techniques were rapidly developed, and have been used to fully reveal the functional components of many animal venoms. In the present study, the cDNA of the salivary gland of Whitmania pigra was sequenced by illumina and the transcriptome was assembled by using Trinity. The proteome were analysed by LC-MS/MS. Based on the data of the transcriptome and the proteome, a potential antiplatelet protein named pigrin was found. Pigrin was cloned and expressed using P. pastoris GS115. The antiplatelet andantithrombotic bioactivities of pigrin were tested by using aggregometer and the rat arterio-venous shunt thrombosis model, respectively. Thebleeding time of pigrin was measured by a mice tail cutting method. The docking of pigrin and protease-activated receptor 1 (PAR1) or collagen were conducted using the ZDOCK Server. Pigrin was able to selectively inhibit platelet aggregation stimulated by PAR1 agonist and collagen. Pigrin attenuated thrombotic formation in vivo in rat, while did not prolong bleeding time at its effective dosage. There are significant differences in the key residues participating in binding of Pigrin-Collagen complex from Pigrin-PAR1 complex. In conclusion,a novel PAR1 inhibitor pigrin was found from the leech Whitmania pigra. This study helped to elucidate the mechanism of the leech for the treatment of cardiovascular disorder.

Research progress on the inhibitors against factor XI / 药学学报

The incidence of thrombotic diseases has increased in the past decade, a factor endangering human health. Currently, antithrombotic drugs used in the clinic have side effects such as inducing bleeding. Data from clinical observation indicate that congenital deficiency of factor XI (FXI) gene decreases the incidence of stroke and deep venous thrombosis, without causing spontaneous bleeding. This unique property of FXI makes it a potential new target for antithrombotic drugs development. Many studies have focused on the discovery of novel inhibitors targeting FXI. This review summarizes the research progress in searching for the inhibitors against FXI.