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

Area of Science:

• Cardiology
• Immunology
• Pharmacology

Background:

• 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.

Purpose of the Study:

• 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.

Main Methods:

• 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.

Main Results:

• 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).

Conclusions:

• 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.