Microb Pathog. 2026 Mar 28:108464. doi: 10.1016/j.micpath.2026.108464. Online ahead of print.

ABSTRACT

Despite the clinical application of Ophiopogon japonicus in idiopathic pulmonary fibrosis (PF), its key anti-fibrotic components and underlying mechanisms remain poorly defined. Using a bleomycin-induced murine PF model, we systematically compared the efficacy of the total extract (OJTE), polysaccharides (OJTP), saponins (OJTS), and flavonoids (OJTF). The active component was further investigated via integrated metagenomics and metabolomics (serum/feces) to decipher the gut-lung axis mechanism. All O. japonicus components attenuated lung injury and collagen deposition, with OJTP demonstrating the most potent efficacy (reducing lung hydroxyproline content by 42.12% (p < 0.01) compared to the model group). Multi-omics analysis revealed that OJTP remodeled the gut microbiota, notably enriching probiotic strains such as Muribaculaceae bacterium (log₂FC = 2.17) and Duncaniella muricolitica (log₂FC = 2.06), as well as the polysaccharide-utilizing species Prevotella sp. MGM2 (log₂FC = 2.79). Concomitantly, OJTP significantly altered host metabolism, upregulating key metabolites including urobilinogen (p < 0.0001) and 5-amino valeric acid betaine (5-AVAB, p < 0.002). These metabolites are implicated in porphyrin and amino acid metabolism, respectively. Correlation networks further established strong associations between these OJTP-modulated microbes and metabolites. Our study first identifies OJTP as the primary bioactive component of O. japonicus against PF. We propose a novel trans-organ mechanism wherein OJTP ameliorates PF via orchestrating a "gut microbiota-metabolite" axis, highlighting the therapeutic potential of targeting polysaccharide-probiotic synergy.

PMID:41912071 | DOI:10.1016/j.micpath.2026.108464

Comb Chem High Throughput Screen. 2026 Mar 11. doi: 10.2174/0113862073398293251205055042. Online ahead of print.

ABSTRACT

INTRODUCTION: This study aimed to investigate the protective effects of Siji Kangbingdu Mixture (SKM) against acute lung injury (ALI) in mice and to elucidate its underlying mechanisms.

METHODS: ALI was induced in Kunming mice via intranasal administration of LPS (5 mg/kg), followed by oral SKM treatment for 7 days. Lung wet-to-dry (W/D) ratio, histopathology, multiomics analysis, and network pharmacology were performed. Key targets and pathways were identified through dynamic KEGG analysis and validated by Western blotting.

RESULTS: SKM treatment ameliorated alveolar hemorrhage, alveolar wall disruption, septal thickening, edema, and inflammatory cell infiltration. Integrated multi-omics analysis revealed that SKM primarily modulated the Ras signaling pathway, reducing the protein expression of Phospho- MEK1/2, Raf1, Phospho-ERK1/2, and RASH/RASK/RASN, thereby contributing to the treatment of ALI.

DISCUSSION: SKM alleviated LPS-induced ALI in mice by inhibiting the Ras pathway, highlighting the pathway's role in ALI pathogenesis. However, due to limitations of the animal model and incomplete validation, further studies combining clinical research and in vitro experiments are needed to confirm its efficacy and mechanism.

CONCLUSIONS: SKM shows potential to ameliorate ALI by suppressing inflammatory responses and reducing local tissue fibrosis. The combination of metabolomics, transcriptomics, and network pharmacology elucidated its mechanism, while Western blot analysis suggested that its therapeutic effect is associated with downregulation of the Ras signaling pathway.

PMID:41830142 | DOI:10.2174/0113862073398293251205055042