A network-based biomarkers discovery of Cold/Hot ZHENG chronic gastritis and Cold/Hot herbs of formulae

Objective: To discover biomarkers and uncover the mechanism of Cold/Hot ZHENG (syndrome in traditional Chinese medicine) chronic gastritis (CG) and Cold/Hot herbs in traditional Chinese medicine (TCM) formulae on systematic biology. Background: CG is a common inflammatory disease and the diagnosis of CG in TCM can be classified into Cold ZHENG (Asthenic Cold) and Hot ZHENG (Excess Hot). However, the molecular features of Cold/Hot ZHENG in CG and the mechanism of Cold/Hot herbs in formulae for CG remained unclear. Methods: Based on data of 35 patients of Cold/Hot ZHENG CG and 3 scRNA-seq CG samples, we conduct analysis with transcriptomics datasets and algorithms, to discover biomarkers for Cold/Hot ZHENG CG. And we collected 25 formulae (with traditional effects related to Cold/Hot ZHENG) for CG and corresponding 89 Cold/Hot herbs (including Warm/Cool herbs) to discover features and construct target networks of Cold/Hot herbs on the basis of network target and enrichment analysis. Results: Biomarkers of Cold/Hot ZHENG CG represented by CCL2 and LEP suggested that Hot ZHENG CG might be characterized by over-inflammation and exuberant metabolism, and Cold ZHENG CG showed a trend of suppression in immune regulation and energy metabolism. And biomarkers of Cold/Hot ZHENG showed also significant changes in the progression of gastric cancer. And biomarkers and pathways of Hot herbs intend to regulate immune responses and energy metabolism, while those of Cold herbs were likely to participate in anti-inflammation effect. Conclusion: In this study, we found that the biomarkers and mechanism of Cold/Hot ZHENG CG and those of Cold/Hot herbs were closely related to the regulation of immune and metabolisms. These findings may reflect the mechanism, build bridges between multiple views of Cold/Hot ZHENG and Cold/Hot herbs, and provide a research paradigm for further achieving precision TCM.