Work

Total secondary saponins from Anemone raddeana suppress pancreatic cancer via Caspase-3/GSDME-mediated pyroptosis

Year: 2026

Type: article

Abstract: Objective Pancreatic cancer (PC) is highly lethal and resistant to current therapies, underscoring the need for novel strategies that target regulated cell death. This study aimed to evaluate the anti-PC efficacy of total secondary saponins (TSS) from Anemone raddeana and elucidate the mechanism by which TSS induces pyroptosis. Methods TSS components were characterized by mass spectrometry. Anti-tumor effects were assessed in vitro using human pancreatic cancer cell lines (PANC-1 and AsPC-1 cells) and in vivo (xenograft mouse model). Integrated multi-omics analyses (network pharmacology, proteomics, metabolomics, bioinformatics) identified core components, targets, and pathways. Key findings were validated by molecular docking, immunohistochemistry, and Western blotting. Results Mass spectrometry identified 17 C-3 monosaccharide triterpenoid saponins in TSS. Both in vitro and in vivo models confirmed that TSS can significantly inhibit PC cell proliferation by inducing pyroptosis through the Caspase-3/gasdermin E (GSDME) pathway. Multi-omics highlighted hederacolchiside A1 as a core compound and revealed its regulation of inflammation, proliferation, and oxidative stress through the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) and nuclear factor- κ B (NF- κ B) signaling pathways. Molecular docking and Western blotting analysis confirmed activation of downstream pyroptosis mechanisms. Conclusion This study demonstrates that TSS suppresses PC progression by regulating Caspase-3/GSDME-mediated pyroptosis through modulation of PI3K/Akt and NF- κ B signaling pathways, supporting its potential as a novel therapeutic candidate for PC.

Source: Chinese Herbal Medicines

DOI: 10.1016/j.chmed.2026.06.010