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Planta Med 2024; 90(10): 801-809
DOI: 10.1055/a-2339-2720
Biological and Pharmacological Activity
Original Papers

Discovery and Characterization of Panaxatriol as a Novel Thrombin Inhibitor from Panax notoginseng Using a Combination of Computational and Experimental Approaches

Xing Wang  ‡
1   Beijing Key Lab of Traditional Chinese Medicine Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing, China
,
Yuqing Ma‡
1   Beijing Key Lab of Traditional Chinese Medicine Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing, China
,
Chunfang Zuo
2   Pharmacy Department, The 989th Hospital of the Joint Logistics Support Force of the Chinese Peopleʼs Liberation Army, Luoyang, China
,
Zixi Zhao
1   Beijing Key Lab of Traditional Chinese Medicine Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing, China
,
Ruonan Ma
1   Beijing Key Lab of Traditional Chinese Medicine Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing, China
,
Lele Wang
3   Key Laboratory of Ethnomedicine (Ministry of Education), School of Pharmacy, Minzu University of China, Beijing, China
,
Yuzhen Fang
3   Key Laboratory of Ethnomedicine (Ministry of Education), School of Pharmacy, Minzu University of China, Beijing, China
,
Yuxin Zhang
3   Key Laboratory of Ethnomedicine (Ministry of Education), School of Pharmacy, Minzu University of China, Beijing, China
,
Xia Wu
1   Beijing Key Lab of Traditional Chinese Medicine Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing, China
› InstitutsangabenGefördert durch: National Natural Science Foundation of China 82374112
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Abstract

Thrombin is a crucial enzyme in the coagulation cascade, and inhibitors of thrombin have been extensively studied as potential antithrombotic agents. The objective of this study was to identify natural inhibitors of thrombin from Panax notoginseng and evaluate their biological activity in vitro and binding characteristics. A combined approach involving molecular docking, thrombin inhibition assays, surface plasmon resonance, and molecular dynamics simulation was utilized to identify natural thrombin inhibitors. The results demonstrated that panaxatriol directly inhibits thrombin, with an IC50 of 10.3 µM. Binding studies using surface plasmon resonance revealed that panaxatriol interacts with thrombin, with a KD value of 7.8 µM. Molecular dynamics analysis indicated that the thrombin-panaxatriol system reached equilibrium rapidly with minimal fluctuations, and the calculated binding free energy was − 23.8 kcal/mol. The interaction between panaxatriol and thrombin involves the amino acid residues Glu146, Glu192, Gly216, Gly219, Tyr60A, and Trp60D. This interaction provides a mechanistic basis for further optimizing panaxatriol as a thrombin inhibitor. Our study has shown that panaxatriol serves as a direct thrombin inhibitor, laying the groundwork for further research and development of novel thrombin inhibitors.

Keywords

thrombin inhibitor - panaxatriol - Panax notoginseng - molecular dynamics - surface plasmon resonance

Supporting Information

    NMR spectra of panaxatriol and molecular docking of the tested compounds are available as Supporting Information.

  • Ergänzendes Material


Publikationsverlauf

Eingereicht: 29. März 2024

Angenommen nach Revision: 05. Juni 2024

Accepted Manuscript online:
05. Juni 2024

Artikel online veröffentlicht:
16. Juli 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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