Investigation of bioactive components and metabolic pathways of Zhen-wu-tang in rat plasma and renal tissue by UPLC-Q-TOF/MS

Introduction: Zhen-wu-tang (ZWT) is a traditional Chinese medicine (TCM) formula for the treatment of several kidney diseases. However, due to the complexity of the TCM formula, there is a lack of accurate knowledge of the chemical constituents of ZWT and its bioactive components, as well as in vivo metabolic pathway studies. Objectives: The chemical composition of ZWT and its bioactive components along with the metabolic pathways were investigated by a combination of chemical profiling and serum pharmacochemistry. Methods: High-resolution ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used to identify the chemical components of ZWT and its bioactive components and metabolites in vivo. Results: As a result, a total of 110 chemical components were identified from ZWT solution, mainly amino acids, alkaloids, gingerols, monoterpene glycosides and terpenoids, and so on. In addition, 24 prototype components and 36 metabolites were detected in rat plasma. Meanwhile, 8 prototype components were detected in rat kidney tissue but no metabolites. Interestingly, 4 of the 28 bioactive components were detected in both plasma and renal tissue, which were atractylenolide III, trimethoxyaconitane, methyl gallate, and paeoniflorin. The metabolic pathways mainly involved Phases I and/or II metabolic reactions such as hydrolysis, oxidation, reduction and hydration, methylation/demethylation, sulphation, glucuronidation, acetylation, and glutathione conjugation. Conclusion: Overall, the present study has comprehensively elucidated the chemical composition of ZWT and its potential bioactive components and metabolites, which provides a basis for the basic study of its pharmacodynamic substances and a reference for the study of the bioactive components of TCM formulae.