Brassisterol A, a new ergosterol from co-cultivation of fungi attenuates neuroinflammation via targeting NLRP3/caspase-1/GSDMD pathway.
Bioorg Chem
; 142: 106955, 2024 01.
Article
em En
| MEDLINE
| ID: mdl-37924754
ABSTRACT
Three new ergosterol derivatives brassisterol A-C (1-3) and two new epimeric bicycle-lactones brassictones A and B (4 and 5), were isolated from the co-cultivation of Alternaria brassicicola and Penicillium granulatum. The absolute configurations of these isolates were confirmed by extensive NMR spectra, TD-DFT ECD calculation, and the single crystal XRD data analysis. Amongst the metabolites, compound 1 exhibited potential anti-Parkinson's disease activity in both MPTP-induced zebrafish and MPP+-induced SH-SY5Y cells. Molecular mechanism studies in vitro showed that 1 attenuated the increase of α-synuclein, NLRP3, ASC, caspase-1, IL-1ß, IL-18, and GSDMD expression in the MPP+ induced PD model. Molecular docking in silico simulations exhibited that 1 was well accommodated to one of the binding pockets of NLRP3 8ETR in an appropriate conformation via forming typical hydrogen bonds as well as possessing a high negative binding affinity (-8.97 kcal/mol). Thus, our work suggested that 1 protected dopaminergic cell from neuroinflammation via targeting NLRP3/caspase-1/GSDMD signaling pathway.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína 3 que Contém Domínio de Pirina da Família NLR
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Neuroblastoma
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article