Int J Biol Macromol. 2026 Sep 25:154618. doi: 10.1016/j.ijbiomac.2026.154618. Online ahead of print.

ABSTRACT

Inonotus obliquus is a medicinal fungus growing on birch bark. A neutral polysaccharide (IOP-W, M_w = 8.222 kDa) was isolated from its crude polysaccharides via sequential DEAE DE-52 cellulose column and Sephadex G-200 gel filtration column chromatography. IOP-W, composed primarily of galactose, glucose, and mannose, was structurally characterized by UV-Vis, FT-IR, GC-MS, and NMR as a glucan containing →4)-α-D-Glcp-(1→, →6)-β-D-Glcp-(1→, →3)-β-D-Glcp-(1→, →4,6)-α-D-Glcp-(1→, terminal α-D-Glcp, and β-D-Glcp reducing end. AFM confirmed its aggregated spherical morphology. IOP-W exerted antitumor activity against MIA PaCa-2 cells by modulating apoptosis and migration. Metabolomics revealed effects on amino acids, alkaloids, lipids, and nucleotides involving 20 pathways, while transcriptomic KEGG analysis showed regulation of MAPK, TNF, and p53 signaling. In vivo investigations employing small animal MRI technology have validated that tumor growth is significantly suppressed in animal models, accompanied by elevated spleen index and improved physiological parameters. Western blotting and immunohistochemistry revealed altered expression of Parp-1, p53, Bax/Bcl-2, p-ERK1/2, p-JNK1, NF-κB, vimentin, and MMP-9. These findings indicate that IOP-W inhibits pancreatic cancer via the p53/MAPK pathway, highlighting its potential as a fungal polysaccharide-based therapeutic candidate.

PMID:42790566 | DOI:10.1016/j.ijbiomac.2026.154618

J Ethnopharmacol. 2026 Mar 26;365:121591. doi: 10.1016/j.jep.2026.121591. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Acute lung injury (ALI) lacks effective therapies. HIF-1α-driven glycolysis can promote histone lactylation and sustain pro-inflammatory (M1) macrophage responses. Daxiefei Decoction (DXFD), a classic traditional Chinese medicine formula, is used for pulmonary inflammatory diseases, but its immunometabolic mechanism remains unclear.

AIM OF THE STUDY: To evaluate the protective efficacy of DXFD against lipopolysaccharide (LPS)-induced ALI and to determine whether it acts through the HIF-1α/glycolysis/histone H3K18 lactylation (H3K18la) axis to regulate macrophage polarization.

MATERIALS & METHODS: DXFD constituents were characterized by UPLC-LTQ-Orbitrap-MS/MS, followed by network pharmacology, molecular docking, and molecular dynamics (MD) simulations. Lung transcriptomics and metabolomics were performed in ALI mice. Efficacy and mechanisms were assessed in LPS-challenged mice and RAW264.7 macrophages using histopathology, ELISA, qRT-PCR, Western blotting, and immunofluorescence. HIF-1α overexpression was used for validation.

RESULTS: DXFD dose-dependently alleviated lung injury and reduced pro-inflammatory cytokines in vivo, and suppressed M1 polarization in vivo and in LPS-stimulated macrophages. Multi-omics indicated activation of HIF-1α-associated inflammatory and glycolytic programs in ALI, which were normalized by DXFD. DXFD decreased glycolytic enzyme expression and reduced histone H3K18 lactylation (H3K18la); these effects were partially reversed by HIF-1α overexpression. Molecular docking and dynamics suggested stable binding of baicalin to HIF-1α.

CONCLUSIONS: DXFD mitigates ALI by dampening HIF-1α-dependent glycolysis and H3K18la, thereby restraining M1-driven inflammatory amplification.

PMID:41903585 | DOI:10.1016/j.jep.2026.121591