Isolation, bioassay and 3D-QSAR analysis of 8-isopentenyl flavonoids from Epimedium sagittatum maxim. as PDE5A inhibitors.
3D-QSAR
8-isopentenyl flavonoid
Phosphodiesterase-5 inhibitor
The processed folium of Epimedium sagittatum Maxim.
cGMP-PKG-Ca2+ signaling pathway
Journal
Chinese medicine
ISSN: 1749-8546
Titre abrégé: Chin Med
Pays: England
ID NLM: 101265109
Informations de publication
Date de publication:
31 Dec 2022
31 Dec 2022
Historique:
received:
23
11
2022
accepted:
23
12
2022
entrez:
31
12
2022
pubmed:
1
1
2023
medline:
1
1
2023
Statut:
epublish
Résumé
As known, inhibition of phosphodiesterase 5 (PDE5) has the therapeutic effect on male erectile dysfunction (ED), and the processed folium of Epimedium sagittatum Maxim. (PFES) characterized by 8-isopentenyl flavonoids is a famous herb for treating ED. However, the main flavonoids inhibitory activities, structure-activity relationship (SAR) and signaling pathway have been not systematically studied so that its pharmacodynamic mechanism is unclear. We aimed to initially reveal the PFES efficacy mechanism for treating ED. For the first time, 6 main 8-isopentenyl flavonoids (1-6) from PFES were isolated and identified. Then based on HPLC detection, we proposed a novel method to screen inhibitors among them. We further analyze the three-dimensional quantitative structure-activity relationship (3D-QSAR) for those inhibitors. The results were verified by cellular effects of the screened flavonoids. Among 6 compounds, Icariin: (1), 2-O''rhamnosylicaridide II (2) and Baohuoside I (3) were identified with significant activities (IC 8-isopentenyl flavonoids could be the main pharmacodynamic substances of PFES in the treatment for ED, and some had significant PDE5A1 inhibitory activities so as to activate cGMP/PKG/Ca
Sections du résumé
BACKGROUND
BACKGROUND
As known, inhibition of phosphodiesterase 5 (PDE5) has the therapeutic effect on male erectile dysfunction (ED), and the processed folium of Epimedium sagittatum Maxim. (PFES) characterized by 8-isopentenyl flavonoids is a famous herb for treating ED. However, the main flavonoids inhibitory activities, structure-activity relationship (SAR) and signaling pathway have been not systematically studied so that its pharmacodynamic mechanism is unclear.
METHODS
METHODS
We aimed to initially reveal the PFES efficacy mechanism for treating ED. For the first time, 6 main 8-isopentenyl flavonoids (1-6) from PFES were isolated and identified. Then based on HPLC detection, we proposed a novel method to screen inhibitors among them. We further analyze the three-dimensional quantitative structure-activity relationship (3D-QSAR) for those inhibitors.
RESULTS
RESULTS
The results were verified by cellular effects of the screened flavonoids. Among 6 compounds, Icariin: (1), 2-O''rhamnosylicaridide II (2) and Baohuoside I (3) were identified with significant activities (IC
CONCLUSION
CONCLUSIONS
8-isopentenyl flavonoids could be the main pharmacodynamic substances of PFES in the treatment for ED, and some had significant PDE5A1 inhibitory activities so as to activate cGMP/PKG/Ca
Identifiants
pubmed: 36587222
doi: 10.1186/s13020-022-00705-5
pii: 10.1186/s13020-022-00705-5
pmc: PMC9805685
doi:
Types de publication
Journal Article
Langues
eng
Pagination
147Subventions
Organisme : Natural Science Foundation of Yichang City
ID : 2019CFB829
Informations de copyright
© 2022. The Author(s).
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