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Effects of hemocoagulase agkistrodon on the coagulation factors and its procoagulant activities.
Drug Des Devel Ther. 2018; 12:1385-1398.DD

Abstract

Objective

Hemocoagulase agkistrodon (HCA), a thrombin-like enzyme (TLE) from the venom of the Chinese moccasin snake (Deinagkistrodon acutus), has been used in clinical practice as a hemostatic compound. The aim of this study was to further investigate the pharmacological properties of HCA.

Materials and methods

Sodium dodecyl sulfate or native polyacrylamide gel electrophoresis (SDS- or N-PAGE) as well as enzyme linked immunosorbent assays (ELISAs) were conducted to study the effects of HCA on the human plasma fibrinogen and prothrombin levels, as well as its in vitro interactions with some coagulation factors. In addition, the bleeding time effects of HCA in the mouse tail-bleeding model as well as its effects on the fibrinogen levels in rabbits were determined in vivo.

Results

In vitro results revealed that HCA exerts its procoagulant activities by hydrolyzing fibrinogen into segments that are easier to be absorbed, reducing the risk of thrombus formation. Besides, HCA could significantly inhibit the activation of prothrombin at the concentration of 0.3 μM. Unexpectedly, we also found that HCA was able to strongly bind to factor X/Xa (in a ratio of 1:1) and thus inhibit the acceleration of active factor X to tissue plasminogen activator-catalyzed plasminogen activation, demonstrating that it could be less likely to lead to thrombus formation. Finally, in vivo results indicated that HCA could significantly shorten the bleeding time in the mouse tail-bleeding model and had no effect on the fibrinogen levels in rabbits.

Conclusion

In summary, HCA, a unique and new family member of TLEs, may become a new clinical drug for the prevention and treatment of hemorrhage due to its unique and complex interactions with the blood system. Clarification of these features will enable us to further understand the mechanism of action of HCA and then promote its further application in clinical practice as a therapeutic drug.

Authors+Show Affiliations

Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People's Republic of China.Department of Pharmacy, Shenzhen Hospital, Southern Medical University, Shenzhen, People's Republic of China.Department of Pharmacy, The Third Affiliated Hospital, Southern Medical University, Guangzhou, People's Republic of China.Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People's Republic of China.Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People's Republic of China.Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People's Republic of China.Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People's Republic of China.Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People's Republic of China.Good Clinical Practice Development, The Third Affiliated Hospital, Southern Medical University, Guangzhou, People's Republic of China.Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People's Republic of China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29872262

Citation

Li, Haixin, et al. "Effects of Hemocoagulase Agkistrodon On the Coagulation Factors and Its Procoagulant Activities." Drug Design, Development and Therapy, vol. 12, 2018, pp. 1385-1398.
Li H, Huang Y, Wu X, et al. Effects of hemocoagulase agkistrodon on the coagulation factors and its procoagulant activities. Drug Des Devel Ther. 2018;12:1385-1398.
Li, H., Huang, Y., Wu, X., Wu, T., Cao, Y., Wang, Q., Qiu, Y., Fu, W., Zhang, Q., & Pang, J. (2018). Effects of hemocoagulase agkistrodon on the coagulation factors and its procoagulant activities. Drug Design, Development and Therapy, 12, 1385-1398. https://doi.org/10.2147/DDDT.S159210
Li H, et al. Effects of Hemocoagulase Agkistrodon On the Coagulation Factors and Its Procoagulant Activities. Drug Des Devel Ther. 2018;12:1385-1398. PubMed PMID: 29872262.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of hemocoagulase agkistrodon on the coagulation factors and its procoagulant activities. AU - Li,Haixin, AU - Huang,Ying, AU - Wu,Xian, AU - Wu,Ting, AU - Cao,Ying, AU - Wang,Qimei, AU - Qiu,Yuchang, AU - Fu,Weiming, AU - Zhang,Qun, AU - Pang,Jianxin, Y1 - 2018/05/23/ PY - 2018/6/7/entrez PY - 2018/6/7/pubmed PY - 2018/12/12/medline KW - FXa KW - TLEs KW - anticoagulant activity KW - coagulation factors KW - procoagulant activity KW - t-PA KW - thrombin-like enzymes SP - 1385 EP - 1398 JF - Drug design, development and therapy JO - Drug Des Devel Ther VL - 12 N2 - Objective: Hemocoagulase agkistrodon (HCA), a thrombin-like enzyme (TLE) from the venom of the Chinese moccasin snake (Deinagkistrodon acutus), has been used in clinical practice as a hemostatic compound. The aim of this study was to further investigate the pharmacological properties of HCA. Materials and methods: Sodium dodecyl sulfate or native polyacrylamide gel electrophoresis (SDS- or N-PAGE) as well as enzyme linked immunosorbent assays (ELISAs) were conducted to study the effects of HCA on the human plasma fibrinogen and prothrombin levels, as well as its in vitro interactions with some coagulation factors. In addition, the bleeding time effects of HCA in the mouse tail-bleeding model as well as its effects on the fibrinogen levels in rabbits were determined in vivo. Results: In vitro results revealed that HCA exerts its procoagulant activities by hydrolyzing fibrinogen into segments that are easier to be absorbed, reducing the risk of thrombus formation. Besides, HCA could significantly inhibit the activation of prothrombin at the concentration of 0.3 μM. Unexpectedly, we also found that HCA was able to strongly bind to factor X/Xa (in a ratio of 1:1) and thus inhibit the acceleration of active factor X to tissue plasminogen activator-catalyzed plasminogen activation, demonstrating that it could be less likely to lead to thrombus formation. Finally, in vivo results indicated that HCA could significantly shorten the bleeding time in the mouse tail-bleeding model and had no effect on the fibrinogen levels in rabbits. Conclusion: In summary, HCA, a unique and new family member of TLEs, may become a new clinical drug for the prevention and treatment of hemorrhage due to its unique and complex interactions with the blood system. Clarification of these features will enable us to further understand the mechanism of action of HCA and then promote its further application in clinical practice as a therapeutic drug. SN - 1177-8881 UR - https://www.unboundmedicine.com/medline/citation/29872262/Effects_of_hemocoagulase_agkistrodon_on_the_coagulation_factors_and_its_procoagulant_activities_ L2 - https://dx.doi.org/10.2147/DDDT.S159210 DB - PRIME DP - Unbound Medicine ER -