ArticleActa pharmacologica Sinica2016
The pyrrolidinoindoline alkaloid Psm2 inhibits platelet aggregation and thrombus formation by affecting PI3K/Akt signaling.
Article in Acta pharmacologica Sinica, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Circulating microRNA expression and their target genes in deep vein thrombosis: A systematic review and bioinformatics analysis.Medicine · 2017Pooled it
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- Gastrodin Alleviates Tau Pathology by Targeting the Alzheimer's Risk Gene FERMT2, Reversing the Reduction in Brain Viscoelasticity.CNS neuroscience & therapeutics · 2025Article
- Network pharmacology analysis and clinical verification ofBiomedical reports · 2025Article
- Clinical significance and underlying mechanism of long non-coding RNA SNHG12 in lower extremity deep venous thrombosis.Clinical and translational science · 2024Article
- Astragaloside IV induces endothelial progenitor cell angiogenesis in deep venous thrombosis through inactivation of PI3K/AKT signaling.Histology and histopathology · 2024Article
- Marine-Fungus-Derived Natural Compound 4-Hydroxyphenylacetic Acid Induces Autophagy to Exert Antithrombotic Effects in Zebrafish.Marine drugs · 2024Article
- Deep sequencing of circulating miRNAs and target mRNAs level in deep venous thrombosis patients.IET systems biology · 2023Article
- Elucidation of Phytochemicals Affecting Platelet Responsiveness in Dangguisu-san: Active Ingredient Prediction and Experimental Research Using Network Pharmacology.Plants (Basel, Switzerland) · 2023Article
- Insights into potential mechanisms of asthma patients with COVID-19: A study based on the gene expression profiling of bronchoalveolar lavage fluid.Computers in biology and medicine · 2022Article
- Fibroblast growth factor-21 as a novel metabolic factor for regulating thrombotic homeostasis.Scientific reports · 2022Article
- Regulation of Key Antiplatelet Pathways by Bioactive Compounds with Minimal Bleeding Risk.International journal of molecular sciences · 2021Review
- FXII regulates the formation of deep vein thrombosis via the PI3K/AKT signaling pathway in mice.International journal of molecular medicine · 2021Article
- Berberine and Its Main Metabolite Berberrubine Inhibit Platelet Activation Through Suppressing the Class I PI3Kβ/Rasa3/Rap1 Pathway.Frontiers in pharmacology · 2021Article
- Purification and Characterization of Novel Collagen Peptides against Platelet Aggregation and Thrombosis fromACS omega · 2020Article
- Pharmacological actions of miltirone in the modulation of platelet function.Acta pharmacologica Sinica · 2019Article
- Amides, Isoquinoline Alkaloids and Dipeptides from the Aerial Parts of Piper mullesua.Natural products and bioprospecting · 2018Article
- Combination of Circulating miRNA-320a/b and D-Dimer Improves Diagnostic Accuracy in Deep Vein Thrombosis Patients.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimPsm2, one of the pyrrolidinoindoline alkaloids isolated from whole Selaginella moellendorffii plants, has shown a potent antiplatelet activity. In this study, we further evaluated the antiplatelet effects of Psm2, and elucidated the underlying mechanisms.
methodsHuman platelet aggregation in vitro and rat platelet aggregation ex vivo were investigated. Agonist-induced platelet aggregation was measured using a light transmission aggregometer. The antithrombotic effects of Psm2 were evaluated in arteriovenous shunt thrombosis model in rats. To elucidate the mechanisms underlying the antiplatelet activity of Psm2, ELISAs, Western blotting and molecular docking were performed. The bleeding risk of Psm2 administration was assessed in a mouse tail cutting model, and the cytotoxicity of Psm2 was measured with MTT assay in EA.hy926 cells.
resultsPsm2 dose-dependently inhibited human platelet aggregation induced by ADP, U4619, thrombin and collagen with IC50 values of 0.64, 0.37, 0.35 and 0.87 mg/mL, respectively. Psm2 (1, 3, 10 mg/kg) administered to rats significantly inhibited platelet aggregation ex vivo induced by ADP. Psm2 (1, 3, 10 mg/mL, iv) administered to rats with the A-V shunt dose-dependently decreased the thrombus formation. Psm2 inhibited platelet adhesion to fibrinogen and collagen with IC50 values of 84.5 and 96.5 mg/mL, respectively, but did not affect the binding of fibrinogen to GPIIb/IIIa. Furthermore, Psm2 inhibited AktSer473 phosphorylation, but did not affect MAPK signaling and Src kinase activation. Molecular docking showed that Psm2 bound to phosphatidylinositol 3-kinase β (PI3Kβ) with a binding free energy of -13.265 kcal/mol. In addition, Psm2 did not cause toxicity in EA.hy926 cells and produced only slight bleeding in a mouse tail cutting model.
conclusionPsm2 inhibits platelet aggregation and thrombus formation by affecting PI3K/Akt signaling. Psm2 may be a lead compound or drug candidate that could be developed for the prevention or treatment of thrombotic diseases.
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