Granulathiazole A protects 6-OHDA-induced Parkinson's disease from ferroptosis via activating Nrf2/HO-1 pathway.
Bioorg Chem
; 147: 107399, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38678778
ABSTRACT
Two pairs of enantiomers (1a-2b), namely (±)-alterpyrone F and (±)-alterpyrone G, along with a rare benzothiazole meroterpenoid granulathiazole A (3, GA), and two undescribed compounds called respectively granulahydeoate (4) and granulaone (5), were obtained from the co-cultivation of Alternaria brassicicola and Penicillium sp. HUBU0120. Exhaustive analyses of NMR, single crystal XRD, Mo2(OAc)4-induced circular dichroism data, and a modified Mosher's method distinguished the absolute configurations of isolates. Bioactive evaluations exhibited that GA possessed promising anti-PD activity in both in vitro and in vivo PD models viz. 6-OHDA-induced SH-SY5Y cells and 6-OHDA-induced zebrafish, respectively. Moreover, our research demonstrated that ferroptosis activated by 6-OHDA was mitigated in PD models after treated with GA. Extensive molecular mechanism studies in PD-modelled cells manifested that GA attenuated the decreased expressions of SLC7A11, GPX4, and FSP-1, and the increased level of ACSL4 via activating Nrf2/HO-1 pathway as well as ameliorated the accumulation of α-synuclein.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oxidopamina
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Heme Oxigenase-1
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Fator 2 Relacionado a NF-E2
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Ferroptose
Limite:
Animals
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Humans
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Estados Unidos