2. Academic Validation
  3. Inhibition of human thrombin by the constituents of licorice: inhibition kinetics and mechanistic insights through in vitro and in silico studies

Inhibition of human thrombin by the constituents of licorice: inhibition kinetics and mechanistic insights through in vitro and in silico studies

  • RSC Adv. 2020 Jan 22;10(7):3626-3635. doi: 10.1039/c9ra09203j.
Cheng-Cheng Shi 1 2,  Tian-Ran Chen 2 3 4,  Qi-Hua Zhang 5,  Ling-Hua Wei 6,  Chao Huang 2,  Ya-Di Zhu 2,  Hai-Bin Liu 3,  Ya-Kun Bai 6,  Fang-Jun Wang 7,  Wen-Zhi Guo 6,  Li-Rong Zhang 1,  Guang-Bo Ge 2 7
Affiliations

Affiliations

  • 1 Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University Zhengzhou Henan China [email protected].
  • 2 Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine Shanghai China [email protected].
  • 3 National Engineering Research Center for Gelatin-based Traditional Chinese Medicine, Dong-E-E-Jiao Co. Ltd. Done-E Shandong China.
  • 4 Department of Gastrointestinal Surgery, The Fifth Affiliated Hospital of Zhengzhou University Zhengzhou China.
  • 5 CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences Shanghai China.
  • 6 Henan Key Laboratory of Digestive Organ Transplantation, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University Zhengzhou China [email protected].
  • 7 CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences Dalian 116023 China.
PMID: 35492646 DOI: 10.1039/c9ra09203j
Abstract

Thrombin inhibition therapy is a practical strategy to reduce thrombotic and cardiovascular risks via blocking the formation of blood clots. This study aimed to identify naturally occurring Thrombin inhibitors from licorice (one of the most popular edible herbs), as well as to investigate their inhibitory mechanisms. Among all tested licorice constituents, licochalcone A was found as the most efficacious agent against human Thrombin (IC50 = 7.96 μM). Inhibition kinetic analyses demonstrated that licochalcone A was a mixed inhibitor against thrombin-mediated Z-Gly-Gly-Arg-AMC acetate hydrolysis, with a K i value of 12.23 μM. Furthermore, mass spectrometry-based chemoproteomic assays and molecular docking simulations revealed that licochalcone A could bind to human Thrombin at both exosite I and the catalytic site. In summary, our findings demonstrated that the Chalcones isolated from licorice were a new class of direct Thrombin inhibitors, also suggesting that licochalcone A was a promising lead compound for developing novel anti-thrombotic agents.

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