Abstract
Purpose: To investigate the comparative anti-thrombotic effects of saffron and Honghua, and also to explore possible mechanisms in thrombosis based on network pharmacology.
 Methods: A network pharmacology model was used for bioactive components, targets and pathways for saffron and HongHua via Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), PharmMapper, Genecard, Uniprot and KEGG databases. In animal experiments, 72 rats were randomly divided into 9 groups: normal control group (NC), model control group (MC), crocetin groups (80, 40, 20 mg/kg), hydroxysafflor yellow A(HSYA) groups (80, 40, 20 mg/kg), and aspirin group (40 mg/kg). Using in vitro thrombosis models and an acute blood stasis model in vivo, the anti-thrombotic effects of these treatments on clotting time, hemorheology parameters, Thromboxane B2 (TXB2), plasmin activator inhibitor (PAI), protein C (PC), protein S (PS), and thrombinantithrombin complex (TAT) were determined and comparisons made for saffron and HongHua.
 Results: Five potential compounds, 16 anti-thrombotic targets and 27 pathways were predicted for saffron, while 22 compounds, 37 disease targets and 35 pathways were found for HongHua (p < 0.05). Pharmacological experiments revealed that crocetin and HSYA had significant effects on thrombus length, thrombus wet/dry mass, whole blood viscosity (WBV), erythrocyte aggregation index (EAI), clotting time and D-dimer for the high and middle groups. Unlike HSYA, crocetin also had significant and dose-dependent effects on PAI, prothrombin fragment 1+2 (F1+2) and PS and had highly significant effects on TXB2 and TAT.
 Conclusion: This research provides a systematic, comprehensive and comparative analysis of component, target and anti-thrombotic pathways of saffron and HongHua based on network pharmacology, and also shows that saffron has more significant anti-thrombotic effect than HongHua.
 Keywords: Saffron; HongHua; Network pharmacology; Anti-thrombosis; Network model
Highlights
Saffron (Crocus sativus L.) is native to Iran and Spain
A total of 70 saffron and 189 HongHua compounds were obtained from the TCMSP platform
The overlap analysis of thrombotic targets showed that 16 targets of saffron were completely included in HongHua, indicating that the 16 targets were common gene targets of saffron, HongHua and thrombus
Summary
Saffron (Crocus sativus L.) is native to Iran and Spain. The main bioactive compounds in saffron are terpenoids, flavonoids, anthraquinones and cyclohexene [1]. Saffron was first recorded in “Ben cao pin hui jing yao” in China. HongHua (Carthamus tinctorius L.), which originated from. China, is rich in flavonoids, pigments, phenolic acids and alkaloids. As representative TCM for cardiovascular diseases, saffron and HongHua are associated with long medicinal histories and rich clinical values [3,4]. In many “Chinese Pharmacy” textbooks, saffron is considered an “additional medicine” of HongHua. chemical studies have revealed only few identical components [2,5]. There is need for comparative studies on their effects on “blood stasis”
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