Exploring the mechanism and phytochemicals in Psoraleae Fructus-induced hepatotoxicity based on RNA-seq, in vitro screening and molecular docking.
Sci Rep
; 14(1): 1696, 2024 01 19.
Article
en En
| MEDLINE
| ID: mdl-38242895
ABSTRACT
Psoraleae Fructus (PF) is a widely-used herb with diverse pharmacological activities, while its related hepatic injuries have aroused public concerns. In this work, a systematic approach based on RNA sequencing (RNA-seq), high-content screening (HCS) and molecular docking was developed to investigate the potential mechanism and identify major phytochemicals contributed to PF-induced hepatotoxicity. Animal experiments proved oral administration of PF water extracts disturbed lipid metabolism and promoted hepatic injuries by suppressing fatty acid and cholesterol catabolism. RNA-seq combined with KEGG enrichment analysis identified mitochondrial oxidative phosphorylation (OXPHOS) as the potential key pathway. Further experiments validated PF caused mitochondrial structure damage, mtDNA depletion and inhibited expressions of genes engaged in OXPHOS. By detecting mitochondrial membrane potential and mitochondrial superoxide, HCS identified bavachin, isobavachalcone, bakuchiol and psoralidin as most potent mitotoxic compounds in PF. Moreover, molecular docking confirmed the potential binding patterns and strong binding affinity of the critical compounds with mitochondrial respiratory complex. This study unveiled the underlying mechanism and phytochemicals in PF-induced liver injuries from the view of mitochondrial dysfunction.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Medicamentos Herbarios Chinos
/
Psoralea
/
Enfermedad Hepática Inducida por Sustancias y Drogas
Tipo de estudio:
Diagnostic_studies
/
Screening_studies
Límite:
Animals
Idioma:
En
Revista:
Sci Rep
Año:
2024
Tipo del documento:
Article
Pais de publicación:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM