An integrated serum pharmacochemistry, network pharmacology, and metabolomics strategy: A study on raw and wine-processed Paeoniae Radix Alba in promoting blood circulation to alleviate blood stasis

Abstract

Paeoniae Radix Alba (PRA) is a traditional Chinese medicine that can be processed with wine to achieve an enhanced effect of promoting blood circulation, thus alleviating blood stasis. However, to date, the changes in the bioactive compounds of PRA before and after wine-processing, as well as the mechanisms of action and the effects on ameliorating blood stasis syndrome (BSS), have not been adequately investigated. Therefore, we systematically elucidated the material basis and mechanisms of action of PRA in the treatment of BSS before and after wine processing by integrating serum pharmacochemistry, network pharmacology, and metabolomics approaches. The wine processing method significantly affected 11 components of PRA, including gallic acid, ethyl gallate, paeoniflorin, and 3-O-methylellagic acid 4-O-β-D-glucopyranoside. Benzoylpaeoniflorin and desbenzoylpaeoniflorin are key serum components of PRA both before and after wine processing. SRC and GAPDH are the central targets through which benzoylpaeoniflorin and desbenzoylpaeoniflorin exert their ameliorative effects on BSS, respectively. The metabolomics results indicated that six metabolic pathways—pyrimidine metabolism, ascorbate and aldarate metabolism, steroid hormone biosynthesis, pentose and glucuronate interconversions, tryptophan metabolism, and lysine degradation—play important roles in the amelioration of BSS by PRA and WPRA. 2’-Deoxycytidine, cortexolone, dihydrocortisol, L-gulonic gamma–lactone, L-uridine, D-ribulose, 4-trimethylammoniobutanoic acid, and indoleacetic acid have been identified as potential biomarkers for the amelioration of BSS by PRA and WPRA. The present study significantly contributes to elucidating the processing mechanism of PRA in “promoting blood circulation to remove blood stasis through wine processing”.