2. Academic Validation
  3. Natural constituents of St. John's Wort inhibit the proteolytic activity of human thrombin

Natural constituents of St. John's Wort inhibit the proteolytic activity of human thrombin

  • Int J Biol Macromol. 2019 Aug 1;134:622-630. doi: 10.1016/j.ijbiomac.2019.04.181.
Ling-Hua Wei 1,  Tian-Ran Chen 1,  Hong-Bo Fang 1,  Qiang Jin 2,  Shui-Jun Zhang 1,  Jie Hou 3,  Yang Yu 2,  Tong-Yi Dou 4,  Yun-Feng Cao 5,  Wen-Zhi Guo 6,  Guang-Bo Ge 7
Affiliations

Affiliations

  • 1 Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University; Henan Key Laboratory of Digestive Organ Transplantation; Zhengzhou Key Laboratory of Hepatobiliary & Pancreatic Diseases and Organ Transplantation; Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou 450001, China.
  • 2 Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
  • 3 Department of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.
  • 4 School of Life Science and Medicine, Dalian University of Technology, Panjin 124221, China.
  • 5 Dalian Runsheng Kangtai Medical Laboratory Co. Ltd., Dalian, China.
  • 6 Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University; Henan Key Laboratory of Digestive Organ Transplantation; Zhengzhou Key Laboratory of Hepatobiliary & Pancreatic Diseases and Organ Transplantation; Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou 450001, China. Electronic address: [email protected].
  • 7 Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: [email protected].
PMID: 31047931 DOI: 10.1016/j.ijbiomac.2019.04.181
Abstract

Thrombin, a multifunctional serine protease responsible for the proteolytic hydrolysis of soluble fibrinogen, plays a pivotal role in the blood coagulation cascade. Currently, Thrombin Inhibitor therapy has been recognized as an effective therapeutic strategy for the prevention and treatment of thrombotic diseases. In this study, the inhibitory effects of natural constituents in St. John's Wort against human Thrombin are carefully investigated by a fluorescence-based biochemical assay. The results clearly demonstrate that most of naphthodianthrones, Flavonoids and Biflavones exhibit strong to moderate inhibition on human Thrombin. Among all tested compounds, hypericin shows the most potent inhibitory capability against Thrombin, with the IC50 value of 3.00 μM. Further investigation on inhibition kinetics demonstrates that hypericin is a potent and reversible inhibitor against thrombin-mediated Z-GGRAMC acetate hydrolysis, with the Ki value of 2.58 μM. Inhibition kinetic analyses demonstrate that hypericin inhibits thrombin-mediated Z-GGRAMC acetate hydrolysis in a mixed manner, which agrees well with the results from docking simulations that hypericin can bind on both catalytic cavity and anion binding exosites. All these findings suggest that hypericin is a natural Thrombin Inhibitor with a unique dianthrone skeleton, which can be used as a good candidate to develop novel Thrombin inhibitors with improved properties.

Keywords

Hypericin; Inhibitory effects; Proteolytic activity; St. John's wort; Thrombin.

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