Chaihu-Shugan-San ameliorates chronic atrophic gastritis by inhibiting nuclear factor-kappa B-mediated inflammation and apoptosis.

The main active chemical components of CSS were identified as lipids and lipid-like molecules, phenylpropanoids, and polyketides using high performance liquid chromatography-mass spectrometry.

• HPLC-MS was the analytical method used to characterize CSS components.
• Three major chemical classes were identified: lipids and lipid-like molecules, phenylpropanoids, and polyketides.
• These components formed the basis for subsequent network pharmacology and molecular docking analyses.

CSS significantly ameliorated MNNG-induced CAG in vivo by inhibiting inflammation and apoptosis.

• CAG was induced using N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in a rat model.
• CSS was tested at two doses: 925 mg/kg/day and 1850 mg/kg/day.
• In vivo experiments demonstrated significant amelioration of CAG pathology at both doses.

Network pharmacology identified core targets of CSS in CAG treatment as TNF, IL-1β, IL-6, BAX, BCL2, caspase-3, caspase-9, and NFKBIA.

• Network pharmacology combined with molecular docking was used to predict potential targets.
• Gene Ontology analysis of these core targets revealed predominant association with the NF-κB signaling complex and BAX apoptotic complex.
• Targets span both inflammatory (TNF, IL-1β, IL-6, NFKBIA) and apoptotic (BAX, BCL2, caspase-3, caspase-9) pathways.

Six compounds in CSS exhibited strong binding affinities with NFKBIA as demonstrated by molecular docking.

• The six compounds identified were baicalin, licoisoflavone B, licochalcone B, glabrone, glycyrrhiza flavonol A, and marmin.
• Molecular docking was used to assess binding affinity between these compounds and the NFKBIA target.
• NFKBIA (IκBα) is a key regulator of the NF-κB signaling pathway, linking these compounds to the proposed anti-inflammatory mechanism.

CSS promoted beneficial changes in the colonic microbial community of rats as assessed by 16S rRNA sequencing.

• 16S rRNA sequencing was used to investigate the impact of CSS on gut microbiota.
• Changes in the colonic microbial community were characterized as beneficial.
• This finding adds a gut microbiota modulation mechanism to CSS's therapeutic effects in CAG.

The NF-κB signaling pathway was identified as the predominant mechanism through which CSS alleviates CAG.

• Gene Ontology analysis linked core targets to the NF-κB signaling complex.
• Both inflammatory and apoptotic arms of NF-κB signaling were implicated.
• The study concluded that CSS alleviated CAG by inhibiting NF-κB-mediated inflammation and apoptosis.