Crocins Ameliorate Experimental Immune Checkpoint Inhibitor-Related Myocarditis by Targeting the Hpx/Nrf2/HO-1...

科学分野:

• Cardiology; Immunology; Pharmacology

背景:

• Immune checkpoint inhibitors (ICIs) can cause myocarditis, a severe adverse event with high mortality.; Crocins, derived from saffron (Crocus sativus L.), possess diverse beneficial bioactivities.

研究 の 目的:

• To investigate the therapeutic potential of crocins in mitigating immune checkpoint inhibitor-related myocarditis.; To elucidate the molecular mechanisms underlying the cardioprotective effects of crocins.

主な方法:

• A subcutaneous xenotransplanted human liver cancer model in nude mice was used to simulate ICI-related myocarditis.; Cardiac function, myocardial damage, autoimmune response, oxidative stress, and inflammation were assessed.; Quantitative proteomics and Western blotting were employed to identify molecular targets.; Molecular docking was performed to predict binding interactions.

主要な成果:

• Crocins significantly improved cardiac function and reduced myocardial damage and autoimmune responses.; Treatment with crocins suppressed oxidative stress and inflammatory reactions in the affected hearts.; Proteomic analysis revealed that crocins act via the Hpx/Nrf2/HO-1 pathway.; Molecular docking identified specific crocin-pathway interactions (crocin I-HO-1, crocin II-Hpx, crocin III-Nrf2).

結論:

• Crocins effectively ameliorate experimental ICI-related myocarditis by modulating the Hpx/Nrf2/HO-1 pathway.; These findings support crocins as a potential therapeutic strategy for ICI-induced myocarditis.; This research provides a basis for the broader clinical application of crocins.