Discovery of neo-Clerodane Diterpenoids from Ajuga campylantha as Neuroprotective Agents against Ferroptosis and Neuroinflammation.
J Nat Prod
; 86(8): 2006-2021, 2023 08 25.
Article
em En
| MEDLINE
| ID: mdl-37566645
ABSTRACT
Twelve new neo-clerodane diterpenoids, eight undescribed methoxy/ethoxy acetal analogues, and one new nor-iridane monoterpenoid were isolated from Ajuga campylantha. Their structures were elucidated using a combination of spectroscopic data, quantum chemical calculations, and X-ray crystallography. This research reveals the distinctive structural features of A. campylantha diterpenes, including distinct C rings and 4,18-double bonds, distinguishing them from diterpenes of other plants in the Ajuga genus. Compound 2 represents the first example of a 19(5â6)-abeo-clerodane formed through a Wagner-Meerwein rearrangement. The isolated compounds were assessed for their neuroprotective effects against RSL3-induced ferroptosis in HT22 cells and LPS-induced neuroinflammation in BV-2 cells. Notably, compound 7 inhibits ferroptosis (EC50 = 10 µM) with a potentially new mechanism of action. The preliminary structure-activity relationship studies revealed that the furan-clerodane diterpenoids possess potential ferroptosis inhibitory activity, while the lactone-clerodanes do not. This study represents the first report of furan-containing clerodanes within the Ajuga genus, providing fresh insights into the phytochemistry and pharmacological potential of A. campylantha.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fármacos Neuroprotetores
/
Ajuga
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Diterpenos Clerodânicos
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Ferroptose
Idioma:
En
Revista:
J Nat Prod
Ano de publicação:
2023
Tipo de documento:
Article