Elucidating the Mechanism of Metabolism of Cannabichromene by Human Cytochrome P450s.
J Nat Prod
; 87(4): 639-651, 2024 04 26.
Article
em En
| MEDLINE
| ID: mdl-38477310
ABSTRACT
Cannabichromene (CBC) is a nonpsychoactive phytocannabinoid well-known for its wide-ranging health advantages. However, there is limited knowledge regarding its human metabolism following CBC consumption. This research aimed to explore the metabolic pathways of CBC by various human liver cytochrome P450 (CYP) enzymes and support the outcomes using in vivo data from mice. The results unveiled two principal CBC metabolites generated by CYPs 8'-hydroxy-CBC and 6',7'-epoxy-CBC, along with a minor quantity of 1â³-hydroxy-CBC. Notably, among the examined CYPs, CYP2C9 demonstrated the highest efficiency in producing these metabolites. Moreover, through a molecular dynamics simulation spanning 1 µs, it was observed that CBC attains stability at the active site of CYP2J2 by forming hydrogen bonds with I487 and N379, facilitated by water molecules, which specifically promotes the hydroxy metabolite's formation. Additionally, the presence of cytochrome P450 reductase (CPR) amplified CBC's binding affinity to CYPs, particularly with CYP2C8 and CYP3A4. Furthermore, the metabolites derived from CBC reduced cytokine levels, such as IL6 and NO, by approximately 50% in microglia cells. This investigation offers valuable insights into the biotransformation of CBC, underscoring the physiological importance and the potential significance of these metabolites.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Canabinoides
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Sistema Enzimático do Citocromo P-450
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article