PUBLICATION
Sirenin and bisabolane sesquiterpenoids from two marine isolates of Penicillium chermesinum with anti-osteoporotic activity by modulating NOD-like receptor signaling pathway
- Authors
- Liu, Y.W., Li, X.J., Hu, X.Y., Li, X.M., Liu, H., Yang, S.Q., Li, H.L., Chen, X.D., Jin, M., Wang, B.G.
- ID
- ZDB-PUB-250919-3
- Date
- 2025
- Source
- Bioorganic chemistry 165: 108993108993 (Journal)
- Registered Authors
- Keywords
- Anti-osteoporotic activity, Marine-sourced fungi, Penicillium chermesinum, Sesquiterpenoids, Sirenins
- MeSH Terms
-
- Animals
- Dose-Response Relationship, Drug
- Mice
- Molecular Structure
- Osteoporosis*/drug therapy
- Osteoporosis*/metabolism
- Penicillium*/chemistry
- Sesquiterpenes*/chemistry
- Sesquiterpenes*/isolation & purification
- Sesquiterpenes*/pharmacology
- Signal Transduction/drug effects
- Structure-Activity Relationship
- Zebrafish
- PubMed
- 40966777 Full text @ Bioorg. Chem.
Citation
Liu, Y.W., Li, X.J., Hu, X.Y., Li, X.M., Liu, H., Yang, S.Q., Li, H.L., Chen, X.D., Jin, M., Wang, B.G. (2025) Sirenin and bisabolane sesquiterpenoids from two marine isolates of Penicillium chermesinum with anti-osteoporotic activity by modulating NOD-like receptor signaling pathway. Bioorganic chemistry. 165:108993108993.
Abstract
Nine unreported (chermesirenins A-I, 1-9) and one known (eupenicisirenin C, 10) sirenin sesquiterpenoids as well as two unreported bisabolane-type sesquiterpenoids (chermebisabolins A and B, 11 and 12) were isolated from two isolates of marine-sourced fungal strains Penicillium chermesinum EN-480 and AS-400, which were obtained as endophytic and endozoic fungi from the marine red alga Pterocladiella tenuis and the marine chiton Liolophura japonica, respectively. The sirenin sesquiterpenoids (1-9) featured with unique 6/3 dicyclic ring system while compounds 8 and 9 are nor-sirenin analogs by degrading the C-12 methyl group. Their structures including stereochemical configurations were confirmed through NMR interpretation, ECD analysis, Mosher's method, X-ray crystallographic diffraction, and quantum chemical calculations. The anti-osteoporotic activity evaluation in the zebrafish osteoporosis model revealed that chermesirenin A (1) could significantly alleviate the reduction of bone fluorescence area and fluorescence density in prednisolone-treated zebrafish. Furthermore, compound 1 could down-regulate the expression of the genes associated with prednisolone-induced osteoclastogenesis, ctsk and tnfrsf11b, to improve bone formation status. Exploration on the mechanism through the transcriptomic analysis showed that compound 1 might act on the NOD-like receptor (NLR) signaling pathway involved in inflammatory responses and bone metabolism regulation, which has not been reported among previous investigations on sesquiterpenoids. These results demonstrated that compound 1 deserved further development as a potential candidate towards the therapy of osteoporotic disease.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping