Systematic characterization of components of Makyo‐kanseki‐to granule and serum metabolomics for exploring its protective mechanism against acute lung injury in lipopolysaccharide‐induced rats

Abstract

Makyo‐kanseki‐to has been used for the treatment of pneumonia, becoming a basic formula for coronavirus disease 2019. However, the chemical profile of Makyo‐kanseki‐to granule and its possible mechanism against acute lung injury from terminal metabolic regulation have been unclear. The aim of this study was to characterize the constituents in Makyo‐kanseki‐to granule and reveal the potential related mechanism of Makyo‐kanseki‐to granule treatment for acute lung injury using a rat model of lipopolysaccharide‐induced acute lung injury. Totally, 78 constituents were characterized based on ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry. Makyo‐kanseki‐to granule could alleviate acute lung injury through modulating rectal temperature, pulmonary edema, histopathology, and processes of inflammatory and oxidative stress. Twenty‐two potential biomarkers in acute lung injury rats were identified by metabolomics based on ultra‐performance liquid chromatography coupled with quadrupole exactive high‐field mass spectrometry. They were mainly involved in amino acids and glycerophospholipid metabolism, which were regulated by Makyo‐kanseki‐to granule. The present results not only increase the understanding of the chemical profile and molecular mechanism of Makyo‐kanseki‐to granule mediated protection against acute lung injury but also provide an experimental basis and new ideas for further development and clinical application of Makyo‐kanseki‐to granule.