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Ginsenoside Rg3-enriched red ginseng extract mitigates sepsis by inhibiting platelet–leukocyte aggregates and regulates thrombo-inflammatory pathways

Year: 2025

Type: article

Abstract: Background: Sepsis is a life-threatening condition characterized by systemic inflammation and thrombo-inflammation, which trigger platelet activation and platelet-leukocyte aggregate (PLA) formation. While Rg3-enriched red ginseng extract (Rg3-RGE) has demonstrated anti-inflammatory and antithrombotic properties, its role in modulating PLAs during sepsis remains poorly understood. Methods: effects of Rg3-RGE were analyzed in a lipopolysaccharide (LPS)-induced murine model of sepsis. Flow cytometry was used to evaluate platelet-leukocyte activation markers. Confocal and scanning electron microscopy (SEM) provided visual evidence of aggregate formation. ELISA was used to quantify plasma levels of tissue factor (TF) and platelet factor 4 (PF4). HPLC analysis revealed the presence of Rb1, Rg3 [20(S) and 20(R)], Rc, Rd, Rf, Rh1, Rb2, and Rg2 [20(S)] in Rg3-RGE. Network pharmacology was employed to identify target interactions and assess their involvement in the thrombo-inflammatory pathway. Results: Rg3-RGE significantly reduced the activated platelets (CD41+CD62P+), platelet-neutrophil aggregates (PNAs; CD41+Ly6G+), and platelet-monocyte aggregates (PMAs; CD41+CD115+). Confocal imaging confirmed a reduction in PNAs. SEM revealed decreased fibrin-like structures and fewer platelet-leukocyte interactions. Rg3-RGE lowered plasma TF levels, indicating a potential effect on the coagulation cascade, though PF4 levels were not significantly altered. Network pharmacology analysis of ginsenosides in Rg3-RGE identified 235 overlapping targets associated with sepsis, inflammation, platelet activation, and PLA formation. Enrichment analysis revealed key thrombo-inflammatory pathways, including platelet activation, MAPK signaling, PI3K-Akt signaling, sphingosine-1-phosphate receptor signaling, and EGFR signaling. Conclusion: Rg3-RGE effectively inhibits platelet-leukocyte aggregate formation and mitigates sepsis-induced platelet-leukocyte interactions.

Source: Journal of Ginseng Research

DOI: 10.1016/j.jgr.2025.10.006