To explore pharmacodynamic substances and mechanism of Xuanfei Baidu Decoction on LPS-induced ALI / ARDS by pharmacochemistry and metabolomics

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Ethnopharmacological relevanceXuanfei Baidu Decoction (XFBD) is made up of five classic prescriptions, which is composed of 13 traditional Chinese medicines, which have the effects of dispersing lung and resolving dampness, clearing heat and evil, purging lung and detoxification. It is used for epidemic diseases caused by damp toxin obstructing lung. In this paper, the endogenous and exogenous metabolites of ALI / ARDS rats after oral administration of XFBD were studied and the material basis and metabolic pathway of XFBD in relieving ALI / ARDS were explained. Materials and MethodsIn this study, UPLC-Q-TOF / MS qualitative analysis method was established, and plasma-urine-faeces pharmacochemistry was used to identify metabolites in plasma, urine and feces after oral administration of XFBD in rats. RT-PCR and immunohistochemistry were used to study the expression of CYP protein in XFBD and monomeric compounds. In addition, the functional mechanism of XFBD in ALI / ARDS rats was elucidated by non-targeted metabolomics. ResultsA total of 77 prototype components and 389 metabolites in plasma, urine and feces were identified by exogenous components, mainly including oxidation, reduction, hydrolysis, glucuronidation, sulfation and other reactions. The results of RT-PCR and immunohistochemistry showed that the activity of CYP was inhibited under the pathological state of ALI/ARDS. At the same time, XFBD and its monomeric compounds can change the metabolic process of drugs in vivo by inducing or inhibiting the activity of CYPs. The metabolic process of drugs in vivo is the result of the combined action of different CYPs. In addition, a total of 33 differential metabolites were identified in plasma, 45 in urine and 14 in feces, which were mainly related to the synthesis and degradation of ketone bodies, phenylalanine metabolism, tyrosine metabolism, histidine metabolism, butyric acid metabolism and other metabolic pathways. ConclusionsThis study conducted a relatively scientific and systematic analysis of XFBD. A UPLC-Q-TOF / MS qualitative analysis method was established to identify 77 prototype components and 389 metabolites in plasma, urine and feces of rats after oral administration of XFBD.An ARDS rat model was established to analyze the pharmacokinetic differences of XFBD in normal and ARDS model rats and its regulation effect on CYPs.Non-targeted metabolomics was used to identify the pattern recognition of ARDS pathological model, the diagnosis of disease and the intervention effect of XFBD on ARDS. Preliminary discussion was conducted to provide a theoretical basis for clinical rational drug use.