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. 2019 Dec;34(1):999-1009.
doi: 10.1080/14756366.2019.1609468.

A novel anti-platelet aggregation target of chinensinaphthol methyl ether and neojusticin B obtained from Rostellularia procumbens (L.) Nees

Songtao Wu  1 , Yanfang Yang  1   2   3 , Bo Liu  1   2   3 , Zhoutao Xie  1 , Weichen Xiong  1 , Pengfei Hao  1 , Wenping Xiao  1 , Yuan Sun  1 , Zhongzhu Ai  1   2   3 , Hezhen Wu  1   2   3
Affiliations

A novel anti-platelet aggregation target of chinensinaphthol methyl ether and neojusticin B obtained from Rostellularia procumbens (L.) Nees

Songtao Wu et al. J Enzyme Inhib Med Chem. 2019 Dec.

Abstract

This study explored the possible bioactive ingredients and target protein of Rostellularia procumbens (L.) Nees. The results of optical turbidimetry revealed that the ethyl acetate extraction obtained from R. procumbens (L.) Nees could inhibit platelet aggregation. Gene chip was used to investigate differentially expressed genes. According to the results of the gene chip, the targets of compounds isolated from the ethyl acetate extraction were predicted by network pharmacology. Computational studies revealed that chinensinaphthol methyl ether and neojusticin B may target the integrin αIIbβ3 protein. The results of Prometheus NT.48 and microscale thermophoresis suggested that the molecular interactions between the two compounds with purified integrin αIIbβ3 protein in the optimal test conditions were coherent with the docking results. To our best knowledge, this is the first report to state that chinensinaphthol methyl ether and neojusticin B target the integrin αIIbβ3 protein.

Keywords: Chinensinaphthol methyl ether; Prometheus NT.48; gene chip; integrin α; microscale thermophoresis; neojusticin B; network pharmacology; platelet aggregation.

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Figures

Figure 1.
Figure 1.
Curves of inhibition of platelet aggregation induced by ADP of (A) 80% ethanol, (B) ethyl acetate, (C) n-butanol, and (D) water extract from Rostellularia procumbens (L.) Nees.
Figure 2.
Figure 2.
Top 10 components of the KEGG pathway and GO enrichment analyses. (A) KEGG pathways. (B) Biological process. (C) Cell components. (D) Molecular function.
Figure 3.
Figure 3.
Network diagram constructed by Cytoscape. (A) Network diagram of active components/target genes/enrichment pathways. (B) Network diagram of target gene/platelet aggregation-related pathways.
Figure 4.
Figure 4.
Thermal unfolding curves. (A) Thermal unfolding curves in the presence of Hepes and pbs. (B) Thermal unfolding curves in the presence of Ttis. Insets show the detergent-dependence of the first unfolding transition midpoint (Tm1).
Figure 5.
Figure 5.
Molecular interaction of integrin αIIbβ3 using NT.LabelFree analysis. (A) MST time traces of 16 different neojusticin B concentrations (ranging from 0.0173 to 71 mM). (B) MST time traces of 16 different chinensinaphthol methyl ether concentrations (ranging from 0.00845 to 69.3 mM). (C) Dependence of the MST signal on the neojusticin B concentration (measured 30 s after turning on heating; data from A). The solid line is a fit with Michaelis–Menten kinetics, yielding an apparent dissociation constant of Kd = 113.47 ± 76.536 nm. (D) Dependence of the MST signal on the chinensinaphthol methyl ether concentration (measured 30 s after turning on heating; data from B). The solid line is a fit with Michaelis–Menten kinetics, yielding an apparent dissociation constant of Kd = 25.22 ± 34.934 nm.
Figure 6.
Figure 6.
Molecular interaction of integrin αIIbβ3 using NT.115 analysis. (A) MST time traces of 16 different neojusticin B concentrations (ranging from 0.000173 to 2.84 mM). (B) MST time traces of 16 different chinensinaphthol methyl ether concentrations (ranging from 0.000677 to 5.55 mM). (C) Dependence of the MST signal on the neojusticin B concentration (measured 30 s after turning on heating; data from A). The solid line is a fit with Michaelis–Menten kinetics, yielding an apparent dissociation constant of Kd = 1.1592 ± 2.5447 μm. (D) Dependence of the MST signal on the chinensinaphthol methyl ether concentration (measured 30 s after turning on heating; data from B). The solid line is a fit with Michaelis–Menten kinetics, yielding an apparent dissociation constant of Kd = 9.8229 ± 0.21873 μm.
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