Carmiseconapine A as a Promising Antidepressant Candidate: An Adenosine 5′-Monophosphate-Activated Protein Kinase Agonist with an Unprecedented Chemical Skeleton
A novel rearranged C<sub>20</sub>-diterpenoid alkaloid, carmiseconapline A (<b>1</b>), featuring a unique 10,20:11,12-di-<i>seco</i>-napelline skeleton with a fused 5/6/5/6/7 pentacyclic ring system, was isolated from <i>Aconitum carmichaelii</i> Debeaux. Compound <b>1</b> 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 <b>1</b> effectively activated adenosine 5'-monophosphate-activated protein kinase (AMPK), protected HT22 cells from mitochondrial dysfunction, and inhibited apoptosis. These findings suggested <b>1</b> as a potential AMPK activator for antidepressant development.
Authors
- Wei‐Ku Zhang (ORCID: https://orcid.org/0000-0001-7367-8136)
- Manni Wang (ORCID: https://orcid.org/0000-0002-3655-6110)
- Jun He (ORCID: https://orcid.org/0000-0001-6242-8107)
- Xue-Ge Pan
- Weifeng Yin
- Jie‐Kun Xu (ORCID: https://orcid.org/0000-0003-1932-207X)
- Yanan Xie (ORCID: https://orcid.org/0000-0002-6883-2781)
- Cong‐Yuan Xia
- Guo‐Yan Zuo
- Kang Ding (ORCID: https://orcid.org/0000-0003-1509-812X)
Institutions
- Beijing University of Chinese Medicine (CN)
- China-Japan Friendship Hospital (CN)
- Institute of Clinical Research (US)
Publication Details
- Journal
- Organic Letters
- Published
- 2025-03-12
- DOI
- https://doi.org/10.1021/acs.orglett.5c00667
- Citations
- 3
- Primary Topic
- Neuroscience and Neuropharmacology Research
- Type
- article
- Field-Weighted Citation Impact
- 2.73