ß-Caryophyllene Confers Cardioprotection by Scavenging Radicals and Blocking Ferroptosis.
J Agric Food Chem
; 72(32): 18003-18012, 2024 Aug 14.
Article
em En
| MEDLINE
| ID: mdl-39088660
ABSTRACT
Ferroptosis is a form of regulated cell death triggered by iron-dependent lipid peroxidation and has been associated with heart diseases. However, there are currently no approved drugs that specifically inhibit ferroptosis in clinical practice, which largely limits the translational potential of this novel target. Here, we demonstrated that ß-caryophyllene (BCP; 150 µM), a natural dietary cannabinoid, protects cardiomyocytes against ferroptotic cell death induced by cysteine deprivation or glutathione peroxidase 4 (GPX4) inactivation. Moreover, BCP preserved the mitochondrial morphology and function during ferroptosis induction. Unexpectedly, BCP supported ferroptosis resistance independent of canonical antiferroptotic pathways. Our results further suggested that BCP may terminate radical chain reactions through interactions with molecular oxygen, which also explains why its oxidation derivative failed to suppress ferroptosis. Finally, oral BCP administration (50 mg/kg, daily) significantly alleviated doxorubicin (15 mg/kg, single i.p. injection)-induced cardiac ferroptosis and cardiomyopathy in mice. In conclusion, our data revealed the role of BCP as a natural antiferroptotic compound and suggest pharmacological modification based on BCP as a promising therapeutic strategy for treating ferroptosis-associated heart disorders.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ferroptose
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Sesquiterpenos Policíclicos
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Camundongos Endogâmicos C57BL
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Agric Food Chem
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China