Analysis of Sulfate Compounds From Sanguisorbae Radix and Its Major Metabolites in Rats by UPLC‐MS/MS and Molecular Docking

RATIONALE: Sanguisorbae Radix that mainly contains tannins and phenolic compounds has been widely used as a traditional Chinese medicine for treating hemafecia, hemorrhoids metrorrhagia and metrostaxis in clinics. However, there is no report about the sulfate phenolic compounds in Sanguisorbae Radix. METHODS: Extraction of Sanguisorbae Radix was separated and purified by polyamide resin and octadecyl silane-bonded silica, which were analyzed by HPLC-IT-TOF/MS. Analysis of rat plasma and urine samples using UPLC-Q-TOF/MS. Finally, the newly discovered sulfate esters in Sanguisorbae Radix were investigated by molecular docking to find out the linkage and the possible mechanism to psoriasis. RESULTS: The chemical structures of methyl-3-O-methylgallate-5-O-sulfate and methyl-3-O-methylgallate were elucidated by the spectral data of HRESIMS and NMR. In addition, 6 sulfate compounds were rapidly identified in Sanguisorbae Radix for the first time, among which 3 sulfate compounds were new natural products. Sixteen prototypes and 11 metabolites were found in rat plasma and urine samples, including 6 sulfate phenolic compounds, and their metabolic pathways in vivo were inferred. Molecular docking technique was used to validate the binding activity of methyl-3-O-methylgallate-5-O-sulfate to psoriasis-related target proteins. CONCLUSIONS: In this study, sulfate phenolic compounds with high content in Sanguisorbae Radix and biological samples were isolated and characterized by modern spectroscopic techniques, which may provide a theoretical basis for the study of the pharmacological activity and quality control of Sanguisorbae Radix and development of sulfate drugs with a similar structure.