PUBLICATION
Isomeric flavonoid aglycones derived from Epimedii Folium exerted different intensities in anti-osteoporosis through OPG/RANKL protein targets
- Authors
- Jiang, J., Xiao, S., Xu, X., Ma, H., Feng, C., Jia, X.
- ID
- ZDB-PUB-180724-8
- Date
- 2018
- Source
- International Immunopharmacology 62: 277-286 (Journal)
- Registered Authors
- Keywords
- Anti-osteoporosis, Molecular docking, OPG/RANKL protein targets, Ovariectomized rats, Zebrafish
- MeSH Terms
-
- Animals
- Bone Density/drug effects
- Disease Models, Animal
- Drugs, Chinese Herbal/chemistry
- Drugs, Chinese Herbal/isolation & purification
- Drugs, Chinese Herbal/therapeutic use*
- Epimedium/chemistry*
- Female
- Flavonoids/chemistry
- Flavonoids/isolation & purification
- Flavonoids/therapeutic use*
- Molecular Docking Simulation
- Osteoporosis/drug therapy*
- Osteoporosis/metabolism
- Osteoprotegerin/genetics
- Osteoprotegerin/metabolism*
- Ovariectomy
- Protein Binding
- RANK Ligand/genetics
- RANK Ligand/metabolism*
- Rats, Sprague-Dawley
- Skeleton/drug effects
- Skeleton/metabolism
- Stereoisomerism
- Zebrafish
- PubMed
- 30036771 Full text @ Int. Immunopharmacol.
Citation
Jiang, J., Xiao, S., Xu, X., Ma, H., Feng, C., Jia, X. (2018) Isomeric flavonoid aglycones derived from Epimedii Folium exerted different intensities in anti-osteoporosis through OPG/RANKL protein targets. International Immunopharmacology. 62:277-286.
Abstract
Two Epimedium-derived isomeric flavonoids, CIT and IT, had the therapeutic effect in osteopenic rats. However, it is difficult to expound their activity differences in anti-osteoporosis. This paper contrasted their anti-osteoporosis activity from the perspective of their affinity to OPG/RANKL protein targets. Molecular docking indicated that both of CIT and IT could interact with the hydrophobic pockets of OPG/RANKL, while CIT was easier and more stable to combine with RANKL. On the contrary, compared with CIT, IT was more inclined to combine with OPG and stay away from combining with RANKL. Subsequently, whether the interaction between isomeric flavonoids and OPG/RANKL targets promoted or suppressed bone resorption was undefined and which was validated by zebrafish embryo and ovariectomized rats in this paper. Compared with IT, the staining area and cumulative optical density of zebrafish skeleton were significantly increased after the treatment of CIT (0.1 μM, p < 0.05). Furthermore, CIT mainly reflected a more significant role in upregulating OPG (p < 0.05), downregulating RANKL (p < 0.05), reducing serum AKP and TRACP level (p < 0.05), enhancing bone biomechanical properties (p < 0.05), increasing bone mineral density (p < 0.05) and improving trabecular bone microarchitecture (p < 0.05) in osteoporotic rats. In conclusion, the combination of isomeric flavonoids (CIT/IT) and OPG/RANKL targets attenuated the excitation effects of OPG or RANKL on RANKL. Because CIT was more firmly combined with RANKL than IT, CIT had stronger anti-osteoporosis effect by inhibiting bone resorption.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping