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Peer-reviewedCC BY-NC-NDChinese herbal medicines

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

4 affiliations
  1. 1School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.
  2. 2Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110032, China.
  3. 3Liaoning Provincial Key Laboratory of Traditional Chinnese Medicine Resources Conservation and Development, Shenyang 110016, China.
  4. 4Liaoning Province Genuine Medicinal Materials Processing Engineering Research Center, Shenyang 110016, China.

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 using 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-κB (NF-κB) 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-κB signaling pathways, supporting its potential as a novel therapeutic candidate for PC.

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BibTeX
@article{han2026total,
  title = {{Total secondary saponins from Anemone raddeana suppress pancreatic cancer via Caspase-3/GSDME-mediated pyroptosis.}},
  author = {Luanwei Han and Mingshu Li and Qiao Li and Anqi Lu and Chongning Lv and Yang Yu and Jincai Lu},
  journal = {Chinese herbal medicines},
  year = {2026},
  month = jun,
  doi = {10.1016/j.chmed.2026.06.010},
  url = {https://europepmc.org/article/MED/42948729},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Total secondary saponins from Anemone raddeana suppress pancreatic cancer via Caspase-3/GSDME-mediated pyroptosis.
AU  - Luanwei Han
AU  - Mingshu Li
AU  - Qiao Li
AU  - Anqi Lu
AU  - Chongning Lv
AU  - Yang Yu
AU  - Jincai Lu
PY  - 2026
DA  - 2026/06/26
JO  - Chinese herbal medicines
DO  - 10.1016/j.chmed.2026.06.010
UR  - https://europepmc.org/article/MED/42948729
AB  - 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 using 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-κB (NF-κB) 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-κB signaling pathways, supporting its potential as a novel therapeutic candidate for PC.
SN  - 1674-6384
SN  - 2589-3610
ER  -