Carmiseconapine A as a Promising Antidepressant Candidate: An Adenosine 5'-Monophosphate-Activated Protein Kinase
Weifeng Yin1,2, Manni Wang2, Xuege Pan2
1Institute of Clinical Medical Sciences & Department of Pharmacy, China-Japan Friendship Hospital, Beijing 100029, People's Republic of China.
Abstract:
A novel rearranged C20-diterpenoid alkaloid, carmiseconapline A (1), featuring a unique 10,20:11,12-di-seco-napelline skeleton with a fused 5/6/5/6/7 pentacyclic ring system, was isolated from Aconitum carmichaelii Debeaux. Compound 1 exhibited remarkable antidepressive activity, being twice as potent as fluoxetine (10 mg/kg) at 0.06 mg/kg in mice. Further mechanism studies showed that 1 effectively activated adenosine 5'-monophosphate-activated protein kinase (AMPK), protected HT22 cells from mitochondrial dysfunction, and inhibited apoptosis. These findings suggested 1 as a potential AMPK activator for antidepressant development.
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