1. Untargeted serum and gastric metabolomics and network pharmacology analysis reveal the superior efficacy of zingiberis rhizoma recens-/euodiae fructus-processed Coptidis Rhizoma on gastric ulcer rats.
- Author
-
Zhang, Zhenkai, Zheng, Yajuan, Zhang, Bingxian, Wang, Ruifeng, Chen, Long, Wang, Yongxiang, Feng, Weisheng, Zheng, Xiaoke, Li, Kai, and Zhou, Ning
- Subjects
- *
CHINESE medicine , *STOMACH tumors , *HERBAL medicine , *PHARMACEUTICAL chemistry , *APOPTOSIS , *PLANT roots , *FLUORESCENT antibody technique , *QUANTITATIVE research , *CELLULAR signal transduction , *PLANT extracts , *MICE , *DRUG efficacy , *ANIMAL experimentation , *WESTERN immunoblotting , *METABOLOMICS , *CYTOKINES , *TUMOR necrosis factors , *INTERLEUKINS , *THERAPEUTICS , *EVALUATION - Abstract
Zingiberis rhizoma recens-/wine-/euodiae fructus-processed Coptidis Rhizoma (CR, zCR/wCR/eCR) are the commonly used processed products of CR in clinic. After being processed with different excipients, the efficacy of CR will change accordingly. I.e., wCR could resolve excessive heat of the upper energizer, zCR could eliminate gastric heat and harmonize the stomach, eCR could smooth the liver and harmonize the stomach. However, the underlying mechanisms were still unclear. To further verify the differential efficacy of the three processed CR products and compare the mechanisms on gastric ulcer. First, a GU model, whose onset is closely related to the heat in stomach and the disharmony between liver and stomach, was established, and the therapeutic effects of zCR/wCR/eCR/CR were evaluated by pathologic observation and measurement of cytokine levels. Second, metabolomics analysis and network pharmacology were conducted to reveal the differential intervening mechanism of zCR/eCR on GU. Third, the predicted mechanisms from metabolomics analysis and network pharmacology were validated using western blotting, flow cytometry and immunofluorescence. zCR/wCR/eCR/CR could alleviate the pathologic damage to varying degrees. In metabolomics research, fewer metabolic pathways were enriched in serum samples, and most of them were also present in the results of gastric tissue samples. The gastroprotective, anti-inflammatory, antioxidant, and anti-apoptotic effects of zCR/wCR/eCR/CR might be due to their interference on histidine, arachidonic acid, and glycerophospholipids metabolism. Quantitative results indicated that zCR/eCR had a better therapeutic effect than wCR/CR in treating GU. A comprehensive analysis of metabolomics and network pharmacology revealed that zCR and eCR exerted anti-GU effects via intervening in five core targets, including AKT, TNF, IL6, IL1B and PPARG. In the validation experiment, zCR/eCR could significantly reverse the abnormal expression of proteins related to apoptosis, inflammation, oxidative stress, gastric function, as well as the PI3K/AKT signaling pathways. zCR and eCR could offer gastroprotective benefits by resisting inflammation and apoptosis, inhibiting gastric-acid secretion, as well as strengthening gastric mucosal defense and antioxidant capacity. Integrating network pharmacology and metabolomics analysis could reveal the acting mechanism of drugs and promote the development of medications to counteract GU. [Display omitted] • Tissue metabolomics are more intuitive than serum metabolomics for GU research. • zCR/eCR could resist inflammation and apoptosis, inhibit gastric acid secretion. • zCR/eCR could strengthen gastric mucosal defense function and antioxidant capacity. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF