Abstract

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.

摘要

1.虹膜美心是一种传统草药，已用于治疗癌症、腹胀、肝硬化和炎症性疾病。I. tectorum Maxim 是如何代谢的，其药理活性的机制基础仍有待确定。

2.本研究旨在阐明I. tectorum Maxim的代谢，并探索其药理活性的机制基础。

3. 在本研究中，通过质谱法从 Wistar 大鼠的胆汁、尿液和粪便样本中鉴定出 51 种代谢物。代谢物主要由葡萄糖醛酸化、硫酸化、甲基化和氨基酸结合形成。

4. 鸢尾素、鸢尾黄素、鸢尾黄素、鸢尾黄素 A、鸢尾黄素 B 和 6-羟基染料木黄酮被确定为潜在的生物活性候选代谢物，通过网络药理学分析检测到 36 个推定靶点和 90 种相互作用。基因集富集分析和复合疾病网络揭示了这些代谢物的靶点来调节与癌症以及心血管、泌尿生殖系统和消化系统疾病相关的重要蛋白质。

5. 分子对接证实了这六种候选生物活性代谢物与碳酸酐酶 IV、VII 和 XII 的相互作用。

6. 总体而言，这些数据为I. tectorum Maxim体内的代谢和药理活性提供了新的见解。