Gastric ulcer (GU) is one of the most commonly diagnosed diseases worldwide, threatening human health and seriously affecting quality of life. Reports have shown that the Chinese herbal medicine Sarcandra glabra (Thunb.) Nakai (SGN) can treat GU. However, its pharmacological effects deserve further validation; in addition, its mechanism of action is unclear. An acute gastric ulcer (AGU) rat model induced by alcohol was used to evaluate the gastroprotective effect of SGN by analysis of the histopathological changes in stomach tissue and related cytokine levels; the potential mechanisms of action of SGN were investigated via serum metabolomics and network pharmacology. Differential metabolites of rat serum were identified by metabolomics and the metabolic pathways of the identified metabolites were enriched via MetaboAnalyst. Furthermore, the critical ingredients and candidate targets of SGN anti-AGU were elucidated. A compound-reaction-enzyme-gene network was established using Cytoscape version 3.8.2 based on integrated analysis of metabolomics and network pharmacology. Finally, molecular docking was applied to verify the acquired key targets. The results showed that SGN exerted a certain gastroprotective effect via multiple pathways and targets. The effects of SGN were mainly caused by the key active ingredients isofraxidin, rosmarinic, and caffeic acid, which regulate hub targets, such as PTGS2, MAPK1, and KDR, which maintain the homeostasis of related metabolites. Signal pathways involved energy metabolism as well as immune and amino acid metabolism. Overall, the multi-omics techniques were proven to be promising tools in illuminating the mechanism of action of SGN in protecting against diseases. This integrated strategy provides a basis for further research and clinical application of SGN.

We aimed to identify the active ingredients and elucidate the underlying mechanism of action of Atractylodes lancea (Thunb.) DC (namely, Cangzhu) for the treatment of gouty arthritis (GA) based on network pharmacology methods. These findings are expected to provide a theoretical basis for the clinical treatment of GA. We used monosodium urate (MSU)-induced GA rats as a model to test the overall efficacy of Cangzhu in vivo. Then, the components of the Cangzhu decoction were analyzed and identified, and we screened the active ingredients and their targets. The GA disease targets were predicted by GeneCards and Disgenet databases and found to overlap in both databases. The STRING database was used to construct a protein-protein interaction network, followed by identification of the hub genes using Network Analyzer. Thereafter, Cytoscape software (version 3.8.2) was applied to construct a network for drug-active ingredient-key targets. Next, we applied cluego, a plug-in of Cytoscape, to perform gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway enrichment analyses. Additionally, molecular docking was used to verify the characteristics of the key candidate components interacting with the hub therapeutic targets. Finally, we established an inflammatory injury model of LPS using RAW264.7 macrophages and used it to experimentally validate the critical active ingredients. Cangzhu effectively protected against gouty arthritis in vivo, and network pharmacology results revealed various active ingredients in Cangzhu, such as wogonin, atractylenolide I and atractylenolide II. These compounds were found to act on 16 hub targets, including tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), interleukin-1β (IL-1β), prostaglandin-endoperoxide synthase 2 (PTGS2), recombinant mitogen-activated protein kinase 14 (MAPK14) and transcription factor p65 (RELA), which have significant effects on regulating inflammatory factors and apoptosis-related pathways to improve the proinflammatory or anti-inflammatory imbalance in the body, and this may be one of the underlying mechanisms of Cangzhu in anti-GA. Our findings revealed that Cangzhu comprises multiple active components that exert various targeted effects during GA treatment. These findings provide relevant insights to illuminate the mechanism of Cangzhu in the treatment of GA and provide a reference for further experimental research.

Plantaginis Semen (PS) is well recognized in traditional Chinese medicine (TCM) and health products. Crude PS (CPS) and salt-processed CPS (SPS) are the two most commonly used decoction pieces of PS, and are included in the 2020 edition of Chinese Pharmacopoeia. Although they all have multiple effects, the mechanisms for treating diseases are different and remain unclear, the processing mechanism of SPS is also indeterminate, which hinders their clinical application to a certain extent. In order to solve these problems and further develop PS in the clinical application. Here, we used saline-loaded model rats for experiments, and utilized an integrated approach consisting of pharmacological methods and metabolomics, which could assess the diuretic impact of CPS and SPS ethanol extracts on saline-loaded rats and elucidate the underlying mechanism. The results showed that CPS and SPS both produced increased urine volume excretion and urine electrolyte excretion, but the levels of aldosterone (ALD) and aquaporin 2 (AQP2) were decreased. And 30 differential metabolites such as linoleic acid, lysoPC(O-18:0), sphingosine-1-phosphate, lysoPC(18:0) were found, mainly involving three metabolic pathways. In conclusion, CPS and SPS both have a diuretic effect, and that of SPS is better. This work investigated the possible diuretic mechanisms of CPS and SPS which may also be the mechanism of PS for anti-hypertension. In addition, a holistic approach provided novel and helpful insights into the underlying processing mechanisms of TCM.

Background: Currently, traditional methods of treating acute gastric ulcer (AGU) have many drawbacks, necessitating an alternative therapy with fewer adverse effects. Atractylodis Macrocephalae Rhizoma (BZ) is known for strengthening the spleen and harmonizing the stomach. BZ processed with Aurantii Fructus Immaturus juice (ZSZBZ), a classic decoction since the Han Dynasty, can enhance the efficacy of BZ. However, the key active components and targets of action of ZSZBZ remain undiscovered. Aim of the study: This study aimed to investigate the bioactive chemical constituents of ZSZBZ against AGU and their possible mechanisms of action, elucidating the scientific content of ZSZBZ processing. Materials and methods: Initially, we examined rat stomach histopathology and conducted ELISA for oxidative stress and inflammation. Subsequently, we investigated underlying mechanisms using metabolomics. Further analysis of potent components and key targets in ZSZBZ was conducted through liquid chromatography-mass spectrometry analysis combined with network pharmacology. Finally, key targets were analyzed by Western blot. Results: ZSZBZ improved gastric histopathology, reversing high alcohol-induced oxidative stress (SOD, CAT) and inflammatory level (TNF-α, IL-6) disorders. This is associated with ZSZBZ’s regulation of amino acid metabolism, energy metabolism, and inflammatory response-related metabolic pathways, along with key targets PTGS2, MAPK1, and KDR. The significant increase in potency of ZSZBZ may be attributed to elevated levels of naringenin, hesperidin, hesperidin, and rhamnoceroside after concoction. Conclusions: Combining metabolomics and network pharmacology, this study elucidated that ZSZBZ enhanced gastroprotection by modulating amino acid metabolism, antioxidant, and inflammation-related targets and pathways, providing insights into the bioactive compounds and potential mechanisms of herbal concoctions.

Background: Gastric cancer (GC) is the fifth most common cancer and the second leading cause of cancer-related deaths worldwide. Due to the lack of specific markers, the early diagnosis of gastric cancer is very low, and most patients with gastric cancer are diagnosed at advanced stages. The aim of this study was to identify key biomarkers of GC and to elucidate GC-associated immune cell infiltration and related pathways.Methods: Gene microarray data associated with GC were downloaded from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were analyzed using Gene Ontology (GO), Kyoto Gene and Genome Encyclopedia, Gene Set Enrichment Analysis (GSEA) and Protein−Protein Interaction (PPI) networks. Weighted gene coexpression network analysis (WGCNA) and the least absolute shrinkage and selection operator (LASSO) algorithm were used to identify pivotal genes for GC and to assess the diagnostic accuracy of GC hub markers using the subjects’ working characteristic curves. In addition, the infiltration levels of 28 immune cells in GC and their interrelationship with hub markers were analyzed using ssGSEA. And further validated by RT-qPCR.Results: A total of 133 DEGs were identified. The biological functions and signaling pathways closely associated with GC were inflammatory and immune processes. Nine expression modules were obtained by WGCNA, with the pink module having the highest correlation with GC; 13 crossover genes were obtained by combining DEGs. Subsequently, the LASSO algorithm and validation set verification analysis were used to finally identify three hub genes as potential biomarkers of GC. In the immune cell infiltration analysis, infiltration of activated CD4 T cell, macrophages, regulatory T cells and plasmacytoid dendritic cells was more significant in GC. The validation part demonstrated that three hub genes were expressed at lower levels in the gastric cancer cells.Conclusion: The use of WGCNA combined with the LASSO algorithm to identify hub biomarkers closely related to GC can help to elucidate the molecular mechanism of GC development and is important for finding new immunotherapeutic targets and disease prevention.