Antiferroptotic properties of allicin and related organosulfur compounds—diallyl disulfide and diallyl trisulfide—from Garlic

Allicin (diallyl thiosulfinate) is an abundant bioactive compound in garlic ( Allium sativum L.) with broad-spectrum antiinflammatory, antifungal, antioxidant, and antitumor properties. The bioactive compounds of garlic including allicin may also help reduce the incidence of various diseases, although the individual contributions and precise mechanisms are still largely unknown. In this study, we reveal that allicin and the closely related compounds diallyl disulfide and diallyl trisulfide (all containing more than one disulfide bond) protect mouse hippocampal HT22 cells against chemically induced ferroptosis, a newly defined form of cell death characterized by iron-dependent lipid peroxidation. In contrast, these organosulfur compounds did not prevent chemically induced apoptosis. The antiferroptotic efficacies of these compounds were strongly associated with prevention of lipid peroxidation and reactive oxygen species production but independent of glutathione upregulation, ferrous iron chelation, and modulation of the nuclear factor erythroid 2 (NF-E2)-related factor-2-antioxidant element response pathway. Additional studies are warranted on the therapeutic potential of allicin and related compounds in garlic for neurodegenerative diseases associated with ferroptosis. • Allicin, diallyl disulfide, and diallyl trisulfide suppress chemically induced ferroptosis. • These garlic-derived organosulfur compounds have no effect on chemically induced apoptosis. • The antiferroptotic properties are independent of iron chelation. • The antiferroptotic properties are associated with reduced ROS and lipid peroxide accumulation.