2. Academic Validation
  3. Baohuoside I induces GSDME-dependent pyroptosis and synergistically inhibits lung adenocarcinoma with cisplatin

Baohuoside I induces GSDME-dependent pyroptosis and synergistically inhibits lung adenocarcinoma with cisplatin

  • Phytomedicine. 2026 Apr:153:157899. doi: 10.1016/j.phymed.2026.157899.
Ying Yang 1,  Luchanghao Zheng 2,  Tao Zhao 1,  Yi Zhang 2,  Ruiguang Luo 1,  Shiyan Xie 1,  Guilan Wen 2,  Zhujun Cheng 3,  Tianyu Han 4
Affiliations

Affiliations

  • 1 Jiangxi Provincial Key Laboratory of Respirtory Diseases, Jiangxi Institute of Respiratory Diseases, The Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China; China-Japan Friendship Jiangxi Hospital, National Regional Center for Respiratory Medicine, Nanchang 330200, Jiangxi, China; The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, Jiangxi Medical College, Nanchang University, Nanchang 330031, Jiangxi, China; School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang City 330031, Jiangxi, China.
  • 2 Jiangxi Provincial Key Laboratory of Respirtory Diseases, Jiangxi Institute of Respiratory Diseases, The Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China; China-Japan Friendship Jiangxi Hospital, National Regional Center for Respiratory Medicine, Nanchang 330200, Jiangxi, China; The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, Jiangxi Medical College, Nanchang University, Nanchang 330031, Jiangxi, China.
  • 3 Medical Centre of Burn Plastic and Wound Repair, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi, China. Electronic address: [email protected].
  • 4 Jiangxi Provincial Key Laboratory of Respirtory Diseases, Jiangxi Institute of Respiratory Diseases, The Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China; China-Japan Friendship Jiangxi Hospital, National Regional Center for Respiratory Medicine, Nanchang 330200, Jiangxi, China; The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, Jiangxi Medical College, Nanchang University, Nanchang 330031, Jiangxi, China. Electronic address: [email protected].
PMID: 41643445 DOI: 10.1016/j.phymed.2026.157899
Abstract

Background: Pyroptosis is a form of inflammatory programmed cell death and has been proven to be a promising therapeutic strategy for Cancer. To date, little is known about the natural product inducers of Pyroptosis. Baohuoside I is a flavonoid compound extracted from Plants of the Epimedium genus and has been reported to have antitumor effects. However, the mechanisms underlying Baohuoside I-induced cell death in lung adenocarcinoma (LUAD) remain unclear.

Purpose: To explore the effects and mechanisms of Baohuoside I-induced cell death in LUAD.

Methods: A cell counting kit-8 (CCK-8) was used to examine the inhibitory effects of Baohuoside I on LUAD cells. Cell death was detected by LDH release and PI staining. Cell membrane separation followed by western blotting and fluorescence microscopy were used to detect the cleavage and membrane translocation of GSDME. RNA Sequencing was used to evaluate changes in overall gene expression.

Results: Baohuoside I induced significant cell death in LUAD cells, and this effect could be blocked by Pyroptosis inhibitors rather than Other cell death inhibitors or ROS scavengers. Further studies demonstrated that Baohuoside I treatment induced the cleavage and membrane translocation of GSDME, leading to Pyroptosis. Through RNA Sequencing analysis, we found that Baohuoside I inhibited the DNA damage repair process and that combined treatment with and cisplatin had a synergistic effect on LUAD.

Conclusion: Baohuoside I is a new Pyroptosis Inducer in LUAD, and combined treatment with Baohuoside I and cisplatin has a synergistic inhibitory effect on LUAD.

Keywords

Baohuoside I; Cisplatin; GSDME; Lung adenocarcinoma; Pyroptosis.

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