Benye Wang, Yuhang Shu, JingJing Wang, Muhammad Farrukh Nisar, Chunli Wang*, Guangzhong Wang* and Kang Xu* Pages 1 - 19 ( 19 )
Background: Stomach Heat Syndrome (SHS) arises from the excessive consumption of spicy and greasy foods, resulting in the infiltration of pathogens and increased gastric activity, ultimately culminating in gastric injury. Coptis chinensis Franch (CC), a frequently employed remedy in Traditional Chinese Medicine (TCM) for dampness elimination, fire purging, and detoxification, has been extensively utilized.
Objective: This study aimed to explore the functional role and in-depth molecular mechanism of CC in treating SHS.
Methods: The CC Alcohol Extract (CCAE) was obtained and analyzed using HPLC. A rat model of SHS hemorrhagic lesions was established using a combination of 8% chili powder and 60% ethanol. After oral administration of CCAE, gastric histology, Myeloperoxidase (MPO), Malondialdehyde (MDA), and Superoxide Dismutase (SOD) levels were evaluated. Further, the gene expressions of Interleukin-6 (IL-6), Interleukin-1β (IL-1β), and Tumor Necrosis Factor-α (TNF-α) were assessed, respectively, using H&E staining, colorimetry, qRT-PCR, and immunohistochemistry analyses. The network pharmacology in multiple databases, transcriptome sequencing, and non-targeted metabolomic analyses were used to identify signal pathways and molecular targets. Subsequent cellular and molecular experiments were also conducted to validate the mechanisms.
Results: The findings demonstrated that the CCAE administration effectively mitigated SHS symptoms in rats and reduced inflammatory cytokines levels and oxidative stress. Berberine (Bbr) was identified as the primary active component responsible for the anti-SHS effects of CC. Additionally, the multi-omics analysis revealed that Bbr primarily regulates amino acid metabolism, unsaturated fatty acid metabolism, the TNF signaling pathway, and the JAK-STAT signaling pathway. Furthermore, Bbr was found to inhibit the phosphorylation of JAK2, STAT3, and p65.
Conclusion: CC alleviated SHS-related gastric disease by suppressing inflammatory responses and enhancing gastric mucosal function through the JAK2-STAT3-NF-κB signaling pathway and amino acid metabolism, with Bbr serving as the key component.
Coptis chinensis Franch extract, stomach-heat syndrome, inflammation, metabolomics, transcriptomics, JAK2-STAT3-NF-κB.