Novel araucarene diterpenes from Agathis dammara exert hypoglycemic activity by promoting pancreatic β cell regeneration and glucose uptake.
10.1016/S1875-5364(25)60856-9
- Author:
Zhewei YU
1
;
Yi ZHANG
2
;
Wenhui WANG
2
;
XinYi WU
2
;
Shunzhi LIU
2
;
Yanlin BIN
2
;
Hongsheng LI
2
;
Bangping CAI
3
;
Zheng WANG
4
;
Meijuan FANG
2
;
Rong QI
5
;
Mingyu LI
6
;
Yingkun QIU
7
Author Information
1. School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China; School of Basic Medical Sciences, Peking University, Beijing 100191, China.
2. School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China.
3. Xiamen Botanical Garden, Xiamen 361003, China.
4. Zhongshan Hospital Affiliated to Xiamen University, Xiamen 361001, China.
5. School of Basic Medical Sciences, Peking University, Beijing 100191, China.
6. School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China. Electronic address: limingyu@xmu.edu.cn.
7. School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China. Electronic address: qyk@xmu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Agathis dammara;
Araucarene;
Diterpenes;
Hypoglycemic;
Pancreatic β Cells
- MeSH:
Zebrafish;
Animals;
Diterpenes/isolation & purification*;
Insulin-Secreting Cells/cytology*;
Glucose/metabolism*;
Hypoglycemic Agents/isolation & purification*;
Molecular Structure;
Structure-Activity Relationship;
Plant Extracts/pharmacology*;
Regeneration/drug effects*
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(4):492-503
- CountryChina
- Language:English
-
Abstract:
In this study, araucarene diterpenes, characterized by a pimarene skeleton with a variably oxidized side chain at C-13, were investigated. A total of 16 araucarene diterpenoids and their derivatives were isolated from the woods of Agathis dammara, including 11 previously unreported compounds: dammaradione (1), dammarones D-G (2, 5, 14, 15), dammaric acids B-F (8-12), and dammarol (16). The structures of these new compounds were elucidated using high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS) and one-dimensional/two-dimensional (1D/2D) nuclear magnetic resonance (NMR), while their absolute configurations were determined through the electronic circular dichroism (ECD) exciton chirality method and Snatzke's method. The hypoglycemic activity of all isolated compounds was evaluated using a transgenic zebrafish model, and a structure-activity relationship (SAR) analysis was conducted. Araucarone (3) and dammaric acid C (9), serving as representative compounds, demonstrated significant hypoglycemic effects on zebrafish. The primary mechanism involves the promotion of pancreatic β cell regeneration and glucose uptake. Specifically, these compounds enhance the differentiation of pancreatic endocrine precursor cells (PEP cells) into β cells in zebrafish.
