Discovery of neo -Clerodane Diterpenoids from Ajuga campylantha as Neuroprotective Agents against Ferroptosis and Neuroinflammation.
Xing PengQingyun TanZhikang ZhangDeyin WuJun XuHuihao ZhouQiong GuPublished in: Journal of natural products (2023)
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(5→6)- 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 (EC 50 = 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 .
Keyphrases
- lps induced
- cell death
- cell cycle arrest
- inflammatory response
- induced apoptosis
- lipopolysaccharide induced
- structure activity relationship
- traumatic brain injury
- high resolution
- molecular docking
- molecular dynamics
- endoplasmic reticulum stress
- cerebral ischemia
- small molecule
- high throughput
- signaling pathway
- molecular dynamics simulations
- cognitive impairment
- magnetic resonance imaging
- risk assessment
- cell proliferation
- machine learning
- electronic health record
- human health
- blood brain barrier
- pi k akt
- brain injury
- case control