02809nas a2200229 4500008004100000245017000041210006900211260001400280300001200294490000700306520202400313653001802337653001602355653001802371653001802389653002502407653003102432100002402463700002802487700002402515856004002539 2026 eng d00aNetwork Pharmacology-based Prediction and In Vivo Validation of Red Ginger and Turmeric Extract Combinations against Hypercoagulability in Isoproterenol-Induced Rats0 aNetwork Pharmacologybased Prediction and In Vivo Validation of R cJune 2026 a139-1490 v183 a

Background: Myocardial infarction is a critical cardiovascular condition often preceded by a hypercoagulable state. Red ginger (Zingiber officinale var. rubrum, ZOR) and turmeric (Curcuma longa L., CL) are recognized for their anticoagulant properties, yet their multi-target pharmacological interactions remain poorly understood. This study aimed to evaluate the anticoagulant potential of ZOR and CL combinations using an integrated network pharmacology and in vivo approach. Methods: Network pharmacology analysis was employed to predict potential molecular targets of ZOR and CL bioactive compounds. For in vivo validation, rats were treated with single extracts (300 mg/kg bw) or combinations (ratios 1:1, 1:3, 3:1), followed by isoproterenol-induced hypercoagulability. Anticoagulant activity was assessed by measuring Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT). Results: Network pharmacology identified 10 key hub proteins, including STAT3, AKT1, and MTOR, indicating a multi-target mechanism. In vivo, isoproterenol effectively induced hypercoagulability. While ZOR (300 mg/kg BW) showed the highest individual potency, all combinations significantly prolonged PT and aPTT (p < 0.05). Based on Chou-Talalay analysis, the interaction was dose-dependent; PT showed nearly additive to synergistic effects (CI: 0.86– 1.07), whereas aPTT exhibited antagonistic trends (CI: 1.06–1.50) at higher ZOR ratios. Consequently, combination effects remained stable without exceeding the most potent single dose. Conclusion: The ZOR and CL combination provides a consistent anticoagulant response through additive interactions, likely mediated by the modulation of the AKT/mTOR signaling axis and coagulation factors. This integration offers a promising, safer multi-target strategy for preventing thrombotic events in myocardial infarction.

10aAnticoagulant10aCoagulation10aCurcuma longa10aIsoproterenol10aNetwork pharmacology10aZingiber officinale rubrum1 aSolihah, Puspa, SD.1 aPasaribu, Ellisa, Clara1 aHaq, Fahmi, Ahsanul uhttps://www.phcogj.com/article/2604