Abstract
In this study; a spectrum–effect relationship analysis combined with a high-performance liquid chromatography–mass spectrometry (LC–MS) analysis was established to screen and identify active components that can inhibit thrombin and factor Xa (THR and FXa) in Salviae Miltiorrhizae Radix et Rhizoma–Chuanxiong Rhizoma (Danshen–Chuanxiong) herbal pair. Ten potential active compounds were predicted through a canonical correlation analysis (CCA), and eight of them were tentatively identified through an LC–MS analysis. Furthermore; the enzyme inhibitory activity of six available compounds; chlorogenic acid; Z-ligustilide; caffeic acid; ferulic acid; tanshinone I and tanshinone IIA; were tested to verify the feasibility of the method. Among them; chlorogenic acid was validated to possess a good THR inhibitory activity with IC50 of 185.08 µM. Tanshinone I and tanshinone IIA are potential FXa inhibitors with IC50 of 112.59 µM and 138.19 µM; respectively. Meanwhile; molecular docking results show that tanshinone I and tanshinone IIA; which both have binding energies of less than −7.0 kcal·mol−1; can interact with FXa by forming H-bonds with residues of SER214; GLY219 and GLN192. In short; the THR and FXa inhibitors in the Danshen–Chuanxiong herbal pair have been successfully characterized through a spectrum–effect relationship analysis and an LC–MS analysis.
Highlights
Thrombin (THR) and factor Xa (FXa), which are members of the Serine Protease family, play critical roles in the coagulation cascade [1]
It has become a trend to search for THR and FXa inhibitors in natural sources to provide a reference for the development of anticoagulant drugs [9]
The inhibitory effects of other DC herbal pair extracts (2:1, 3:1, 5:1, 1:5, 1:3 and 1:2) on FXa are weaker than the DS extract
Summary
Thrombin (THR) and factor Xa (FXa), which are members of the Serine Protease family, play critical roles in the coagulation cascade [1]. THR catalyzes the transformation of soluble fibrinogen into insoluble fibrin in response to a vascular injury, leading to the formation of a clot [2]. It is worth mentioning that the formation of THR can be reduced by inhibiting its activity to prevent the expansion of a thrombus [3]. Due to the importance of THR and FXa in the formation of thrombosis, inhibiting their activity is a feasible strategy for the treatment of thrombotic diseases [5]. It has become a trend to search for THR and FXa inhibitors in natural sources to provide a reference for the development of anticoagulant drugs [9]
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