Ligustilide from Radix Angelica Sinensis prevents the migration of vascular smooth muscle A7r5 cells based on network pharmacology and experimental verification

Abstract

ObjectiveLigustilide (Lig), a major component of Radix Angelica Sinensis, exhibits a protective effect on many cardiovascular diseases. Our previous study showed that Lig inhibited the proliferation of vascular smooth muscle cells. In this study, we aimed to investigate the effect of Lig on the migration of vascular smooth muscle A7r5 cells induced by Angiotensin II (Ang II) and explore the mechanism underlying based on network pharmacology. MethodsIn this study, scratch-wound healing assay and transwell migration assay were used to assess the migration activity of Lig on Ang II-induced vascular smooth muscle A7r5 cells, and network pharmacology method was used to predict the possible target molecules. Western blot analysis, Gelatin zymography assay, and small interfering RNA (siRNA) were used to determine the underlying mechanism of Lig on the migration in Ang II-induced A7r5 cells. ResultsWe found that Lig could prevented the migration induced by Ang II in A7r5 cells, which could be associated with c-Myc and MMPs from the results of network pharmacology. Our results revealed that Lig could significantly reduce the increase in the protein expression levels of c-Myc and MMP-2 in Ang II-induced A7r5 cells, but not affect the protein expression levels of MMP-9. Our data further showed that c-Myc siRNA, just as Lig, could obviously inhibit the cell migration accompanied by decreased MMP-2 expression. ConclusionThese findings suggested the anti-migratory effect of Lig could be associated with the c-Myc/MMP-2 pathway, and Lig administration had a promising potential for preventing cardiovascular diseases.