Integrated transcriptomics and lipidomics investigation of the mechanism underlying the gastrointestinal mucosa damage of Loropetalum chinense (R.Br.) and its representative component

•Flavonoids and polyphenols are the main components type of Loropetalum chinensis (R.Br) oliv leaves (Bhjm).•Bhjm and ellagic acid (EA) exerted a therapeutic effect against 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced gastrointestinal mucosa damage (GMD) in terms of inflammation and mucosal repair.•Molecular mechanism was investigated by multiomics approaches.•Bhjm and EA may exert therapeutic effects by regulating key gene klf4, hist1h2ba, and differential lipid metabolites, including phosphatidylcholine (PC) and triglyceride (TG). Loropetalum chinensis (R.Br) Oliv (Bhjm), a Chinese folk herbal medicine, was traditionally used in the treatment of wound bleeding and skin ulcers. A new drug named JIMUSAN granules used for gastrosia was developed by our group, and clinical trials have been approved. However, as the principal herb, the material basis and underlying mechanisms of Bhjm in attenuating gastrointestinal mucosa damage (GMD) remain to be systemically illuminated. An integrated strategy was used to explore the therapeutic effects and mechanisms of Bhjm and ellagic acid (EA) on GMD zebrafish, using network pharmacology, transcriptomics, lipidomics, and real-time quantitative PCR (RT-qPCR) verification. First, network pharmacological analysis was used to infer the major effective constituents and targets of Bhjm. Ultra high performance liquid chromatography-linear ion trap/orbitrap high resolution mass spectrometry (UHPLC-LTQ-Orbitrap HRMS) and ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) were employed to identify the chemical constituents and quantify the different types of constituents. Second, zebrafish model of GMD was established by using 2,4,6-trinitrobenzenesulfonic acid (TNBS) to evaluate the efficacy of Bhjm and EA. The potential mechanism was examined by integrated transcriptomics and lipidomics analysis. Finally, validation tests were implemented using RT-qPCR. In this study, targets indentified by network pharmacology were related to inflammation and mucosal damage. Ten representative components that interacted with these targets were simultaneously determined by UHPLC-MS/MS. Sixty four compounds were identified or tentatively characterized, most of which were flavonoids and polyphenols. Bhjm and EA alleviated mucosal damage and reduced inflammation in a TNBS-induced zebrafish GMD model, indicating that EA was the main active compounds. Eight common differentially expressed genes were downregulate