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Isolation, bioassay and 3D-QSAR analysis of 8-isopentenyl flavonoids from Epimedium sagittatum maxim. as PDE5A inhibitors.
- Source :
-
Chinese Medicine . 12/31/2022, Vol. 17 Issue 1, p1-18. 18p. - Publication Year :
- 2022
-
Abstract
- 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: 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: The results were verified by cellular effects of the screened flavonoids. Among 6 compounds, Icariin: (1), 2-Oʹʹrhamnosylicaridide II (2) and Baohuoside I (3) were identified with significant activities (IC50 = 8.275, 3.233, 5.473 μM). Then 3D-QSAR studies showed that the replacement of C8 with bulky steric groups as isopentenyl, C3 with positive charge groups and C4' with a hydrogen bond acceptor substituent could increase inhibitory effects. In contrast, the substitution of C7 with bulky steric groups or hydrophilic groups tended to decrease the efficacies. And compounds 1, 2, 3 could increase cGMP level and decrease cytoplasmic Ca2+ of rat corpus cavernosum smooth muscle cells (CCSMCs)by activating PKG. Conclusion: 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/Ca2+ signaling pathway in CCSMCs, that was related to the substituents at the key sites such as C8, C3, C4ʹ and C7 in the characteristic compounds. [ABSTRACT FROM AUTHOR]
- Subjects :
- *PHYTOTHERAPY
*DRUG efficacy
*FLAVONOIDS
*IMPOTENCE
*HIGH performance liquid chromatography
*SMOOTH muscle
*HERBAL medicine
*ANIMAL experimentation
*RATS
*CELLULAR signal transduction
*PLANT extracts
*BIOLOGICAL assay
*MOLECULAR structure
*PHOSPHODIESTERASE inhibitors
*CHINESE medicine
THERAPEUTIC use of plant extracts
Subjects
Details
- Language :
- English
- ISSN :
- 17498546
- Volume :
- 17
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Chinese Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 161076883
- Full Text :
- https://doi.org/10.1186/s13020-022-00705-5