Identification of the metabolites produced following Iris tectorum Maxim oral administration and a network pharmacology-based analysis of their potential pharmacological properties

1. Iris tectorum Maxim is a traditional herbal medicine that has been used to treat cancer, abdominal distension, hepatic cirrhosis, and inflammatory diseases. How I. tectorum Maxim is metabolised and the mechanistic basis for its pharmacological activity remain to be defined. 2. This study was designed to clarify the metabolism of I. tectorum Maxim and to explore the mechanistic basis for its pharmacological activity. 3. In the present study, 51 metabolites were identified via mass spectrometry in samples of bile, urine, and faeces from Wistar rats. Metabolites were mainly formed by glucuronidation, sulphation, methylation, and amino acid conjugation. 4. Tectoridin, tectorigenin, irigenin, iristectorigenin A, iristectorigenin B, and 6-hydroxygenistein were identified as potentially be bioactive candidate metabolites for which 36 putative targets and 90 interactions were detected through a network pharmacology analysis. Gene set enrichment analyses and compound-disease networks revealed the targets of these metabolites to regulate important proteins associated with cancer as well as cardiovascular, urogenital, and digestive system diseases. 5. Molecular docking confirmed the interactions of these six candidate bioactive metabolites with carbonic anhydrase IV, VII, and XII. 6. Overall, these data offer new insights into the metabolism and pharmacological activity of I. tectorum Maxim in vivo.