2. Academic Validation
  3. Pharmacological effects and mechanism of Ilexsaponin A1 in modulating platelet function

Pharmacological effects and mechanism of Ilexsaponin A1 in modulating platelet function

  • J Ethnopharmacol. 2025 Mar 26:344:119564. doi: 10.1016/j.jep.2025.119564.
Yu-Min Zhang 1,  Qi Luo 1,  Meng Lu 1,  Xue Gong 1,  Ya-Wei Guo 1,  Xiang-Bin Zeng 1,  Ying Zhu 2,  Dan Shu 3,  Yue-Ling Lin 1,  Xu-Ran Guo 1,  Zhang-Yin Ming 4
Affiliations

Affiliations

  • 1 Department of Pharmacology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, China; Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Wuhan, China.
  • 2 Department of Pharmacy, Wuhan Hospital of Traditional Chinese and Western Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 3 Institute of Cardiovascular Diseases, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, China.
  • 4 Department of Pharmacology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, China; Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Wuhan, China; Tongji-Rongcheng Center for Biomedicine, Huazhong University of Science and Technology, Wuhan, China. Electronic address: zyming@hust.edu.cn.
PMID: 40015536 DOI: 10.1016/j.jep.2025.119564
Abstract

Ethnopharmacological relevance: Ilex pubescens Hook. & Arn. is a traditional Chinese medicine for promoting blood circulation. Ilexsaponin A1 (IsA), a monomer of the compound, exhibits pro-angiogenic, anti-apoptotic and anti-inflammatory activities. Nevertheless, the pharmacological effects and specific mechanisms by which IsA affects platelets remain unknown.

Aim of the study: This study aims to investigate the antiplatelet effects of IsA and the underlying molecular mechanisms.

Materials and methods: Platelet aggregation and ATP release were assessed using platelet aggregometry. Flow cytometry was employed to evaluate the exposure of P-selectin, Integrin αⅡbβ3 activation and calcium mobilization. Fluorescence microscopy was applied to observe platelet spreading. Clot retraction was imaged by digital camera. Protein phosphorylation regulation of major signaling pathways in platelets was determined by immunoblotting analysis. Doppler flowmetry was used to investigate the in vivo effect of IsA on FeCl3-induced carotid artery injury model. Tail vein transection was used to measure bleeding time.

Results: IsA dose-dependently inhibited platelet aggregation and ATP release induced by collagen, U46619, Thrombin and ADP. It also suppressed thrombin-induced P-selectin exposure and PAC-1 binding. Furthermore, IsA inhibited intracellular CA2+ mobilization and the inward flow of extracellular CA2+. It also influenced Integrin αⅡbβ3 outside-in signaling pathways, including the inhibition of platelet spreading, clot retraction and phosphorylation of outside-in signaling molecules. In addition, IsA suppressed the phosphorylation of Syk-PLCγ2, PI3K-Akt-GSK3β and MAPKs proteins, which are downstream effectors of the collagen and Thrombin receptors.

Conclusion: IsA inhibited platelet function and thrombus formation. This has potential to be developed into a novel therapeutic agent for the treatment of thrombotic diseases.

Keywords

Anti-Platelet drug; FeCl(3)-Induced thrombosis model; Ilexsaponin A1; Inside-out and outside-in signal transduction; Platelet aggregation and release.

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