Deciphering the multi-target mechanism of Magnolia officinalis in irritable bowel syndrome with diarrhea: A combined network pharmacology, machine learning, and in vivo validation study

Background The bark of Magnolia officinalis Rehder & E. Wilson, used in TCM for abdominal distension, pain, and diarrhea, aligns with IBS-D symptoms. It is now supported by evidence for its multi-component, multi-target action. This study aims to elucidate the core bioactive components and their mechanisms against IBS-D. To achieve this, we employed an analytical strategy that uses machine learning to refine network pharmacology predictions, rather than relying on network pharmacology alone. Materials and methods This study integrates network pharmacology and machine learning to identify core therapeutic targets. The affinity of the components for these targets is validated through molecular docking studies. An IBS-D rat model was used to evaluate the effects of the core components (magnolol, honokiol, obovatol) on behavior (sucrose preference, open field), gastrointestinal motility, intestinal permeability, serum inflammatory cytokines (ELISA), and core target gene expression (qRT-PCR). Results Computational analyses identified five potential active components, including magnolol (Mag), honokiol (Hnk), and obovatol (Obo), and eight core targets (e.g., EGFR, MET) involved in PI3K-Akt and FoxO pathways. Molecular docking confirmed stable binding. In vivo, Hnk, Mag, and Obo ameliorated IBS-D-related anxiety-like behavior, intestinal hypermotility, and barrier dysfunction. They significantly downregulated EGFR and MET expression and reduced serum levels of IL-8, TNF-α, and MyD88. Notably, all treatments increased fecal short-chain fatty acids (SCFAs). Conclusion The core components of M. officinalis , represented by Hnk, Mag, and Obo, alleviate IBS-D likely through a multi-target mechanism involving suppression of EGFR/MET and subsequent PI3K-Akt signaling, leading to reduced inflammation, improved barrier function, and modulated gut-brain axis. This provides a mechanistic foundation for the traditional use of M. officinalis in treating gastrointestinal disorders.