Metabolites analysis of plantamajoside based on gut microbiota-drug interaction

Background: Plantaginis Herba (Plantago asiatica L.) has the effects of clearing heat and diuresis, oozing wet and drenching. As the main active components of Plantaginis Herba (Plantago asiatica L.), plantamajoside have a wide range of antitumor activities but very low bioavailability. The process of interacting between plantamajoside and gut microbiota remains unclear.Purpose: To illustrate the process of interacting between plantamajoside and gut microbiota based on high -resolution mass spectrometry and targeted metabolomics methods.Study design and methods: This experiment was divided into two parts. First, metabolites produced from plan-tamajoside by gut microbiota were identified and quantified based on high-resolution mass spectrometry and LC-MS/MS. Additionally, stimulation of plantamajoside on gut microbiota-derived metabolites was determined by targeted metabolomics and gas chromatography.Results: We first found that plantamajoside was rapidly metabolized by gut microbiota. Then, we identified metabolites of plantamajoside by high-resolution mass spectrometry and speculated that plantamajoside was metabolized into five metabolites including calceolarioside A, dopaol glucoside, hydroxytyrosol, 3-(3-hydrox-yphenyl) propionic acid (3-HPP) and caffeic acid. Among them, we quantitatively analyzed four possible me-tabolites based on LC-MS/MS and found that hydroxytyrosol and 3-HPP were final products by the gut microbiota. In addition, we studied whether plantamajoside could affect the short-chain fatty acid (SCFA) and amino acid metabolites. We found that plantamajoside could inhibit the acetic acid, kynurenic acid (KYNA) and kynurenine (KN) produced by intestinal bacteria and promote the indole propionic acid (IPA) and indole formaldehyde (IALD) produced by intestinal bacteria.Conclusion: An interaction between plantamajoside and gut microbiota was revealed in this study. Unlike the traditional metabolic system, the special metabolic characteristics of plantamajoside in gut microbiota was found. Plantamajoside was metabolized into the following active metabolites: calceolarioside A, dopaol gluco-side, hydroxytyrosol, caffeic acid and 3-HPP. Besides, plantamajoside could affect SCFA and tryptophan meta-bolism by gut microbiota. Especially, the exogenous metabolites hydroxytyrosol, caffeic acid and endogenous metabolites IPA may have potential association with the antitumor activity of plantamajoside.

Automated summary

This study revealed the interaction between plantamajoside and gut microbiota using high-resolution mass spectrometry and targeted metabolomics methods. The results showed that plantamajoside was rapidly metabolized into various active metabolites in the gut microbiota. Moreover, plantamajoside was found to affect short-chain fatty acid and tryptophan metabolism. These findings are significant for understanding the pharmacological effects of plantamajoside.