Screening of Potential Thrombin and Factor Xa Inhibitors from the Danshen–Chuanxiong Herbal Pair through a Spectrum–Effect Relationship Analysis

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.

Guanxinning Tablet Attenuates Coronary Atherosclerosis via Regulating the Gut Microbiota and Their Metabolites in Tibetan Minipigs Induced by a High-Fat Diet

“…GXNT is clinically used for treating CHD and ischemic cardiomyopathy with significant curative effects [ 13 ]. Our previous pharmacological experiments confirmed that GXNT has the functions of reducing whole blood viscosity, improving blood rheology abnormalities, antimyocardial ischemia, antithrombosis, and vasodilation [ 14 – 19 ].…”

Spectrum–Effect Relationships as an Effective Approach for Quality Control of Natural Products: A Review

“…Wang et al prepared four kinds of Lichong Shengsui Yin extracts by different extraction methods and then mixed each extract in different proportions to prepare nine kinds of mixture and compared the anti-ovarian cancer activity of different component compatibility and the main active ingredients to play the efficacy through the spectrum-effect relationships [98]. Similar studies have also been conducted on the optimization of nine different ratios of Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma herbal pairs (1:0, 1:1, 2:1, 3:1, 5:1, 1:5, 1:3, 1:2 and 0:1) [99], and the optimization of extracts of Curcumae Rhizoma-Sparganii Rhizoma with different polar elution fractions (water, 20%, 40%, 60%, 80%, and 95% ethanol) [100]. In the optimization of component compatibility, one study used Fe 2+ instead of Hg 2+ to improve Zhusha Anshen Pill to create Tieshuang Anshen Prescription, which not only improved the sedative and hypnotic effect of the compound but also avoided the toxicity of Hg 2+ in the previous prescription [101].…”