Pharmacodynamics, metabolomics and pathological studies on mechanisms of traditional benefits of Angelica sinensis in blood circulation

Abstract

Angelica sinensis is a rich source of medically important active molecules that need in-depth understanding on its action mechanisms. Therefore, through pharmacodynamics, metabolomics, and network pharmacology, the traditional benefits of A. sinensis in blood circulation was studied using 24 randomly selected Sprague-Dawley (SD) rats. Measurement of the blood rheological parameters for whole blood viscosity (WBV) and plasma viscosity (PV), and inspection of the heart and lung tissues pathological changes were undertaken using molecular and bioinformatic techniques. Multivariate statistical analysis and establishment of the model of the relationship between metabolite expression and sample categories to test the prediction of sample categories were performed. Screening was undertaken to find the potential metabolites for A. sinensis to treat blood stasis syndrome and find related metabolic pathways. Active ingredients of A. sinensis and targets and building of an “effect component-target” network was undertaken, A. sinensis was confirmed to improve blood stasis syndrome in rats and improve heart and lung pathology to varying degrees. Compared with the blood stasis model group, A. sinensis significantly reduced WBV and PV in hemorheology (p<0.05, p<0.01) and regulated blood stasis-induced changes in 22 metabolites including alpha-D-glucose, L-isoleucine, creatine and acetylcarnitine, which are involved in the metabolism of linoleic acid, linolenic acid, phenylalanine, ascorbic acid and uronic acid. Using the network pharmacology to build a "component-target-pathway" network of A. sinensis, 62 active ingredients, 169 active proteins and 18 metabolic pathways were obtained, among which linoleic acid metabolism, ascorbic acid and uronic acid metabolism were consistent with the metabolic pathways obtained by metabolomics.