Exploring the anti-inflammatory activity of fupenzic acid using network pharmacology and experimental validation
Abstract Crataegus azarolus L. (Rosaceae), commonly known as Mediterranean hawthorn, has long been valued in Traditional Medicine for treating cardiovascular and inflammation-related diseases, including diabetes, cancer, and rheumatism. Pharmacological benefits of Crataegus azarolus L. are notably l...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-04-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-98901-4 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849713491300057088 |
|---|---|
| author | Djoudi Boukerouis Irene Cuadrado Nadjet Debbache Benaida Ana Estévez-Braun Beatriz de las Heras Angel Amesty Sonsoles Hortelano |
| author_facet | Djoudi Boukerouis Irene Cuadrado Nadjet Debbache Benaida Ana Estévez-Braun Beatriz de las Heras Angel Amesty Sonsoles Hortelano |
| author_sort | Djoudi Boukerouis |
| collection | DOAJ |
| description | Abstract Crataegus azarolus L. (Rosaceae), commonly known as Mediterranean hawthorn, has long been valued in Traditional Medicine for treating cardiovascular and inflammation-related diseases, including diabetes, cancer, and rheumatism. Pharmacological benefits of Crataegus azarolus L. are notably linked to its anti-inflammatory properties. Fupenzic acid, a pentacyclic triterpene isolated from its leaves, holds significant pharmacological potential that remains elusive. This study investigates the unexplored capacity of fupenzic acid as a promising anti-inflammatory agent. Using a multidisciplinary approach that integrates network pharmacology, molecular docking, in vitro assays, and predictive in silico analyses of drug-like properties, ADME, and toxicity, the mechanisms and properties of fupenzic acid have been elucidated. Network pharmacology analysis identified the potential targets for fupenzic acid, with enrichment analyses revealing key processes like inflammatory response, cytokine signaling, innate immune system, and MAPK cascade regulation. Transcription factors such as RELA, SP1, and NFKB1 were predicted to play crucial roles in its therapeutic effects. PPI network analysis underscored NF-κB as a central hub, linking these pathways to its anti-inflammatory effects. In vitro experiments demonstrated that fupenzic acid effectively suppressed inflammatory mediators like NOS-2 and COX-2, through the NF-κB pathway. Molecular docking further confirmed its favorable interaction with NF-κB, reinforcing its mechanism of action. Additionally, in silico ADMET profiling revealed favorable drug-like properties including pharmacokinetics and toxicity profiles, emphasizing its suitability as a drug candidate. This study represents a major step forward in understanding the therapeutic potential of fupenzic acid, establishing it as a distinctive and promising anti-inflammatory agent. The findings identified it as a pharmacological agent for clinical development targeting inflammation-driven diseases and also provide a foundation for future translational research. |
| format | Article |
| id | doaj-art-d211f8d3df4e4e71941d5856e327607f |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-d211f8d3df4e4e71941d5856e327607f2025-08-20T03:13:57ZengNature PortfolioScientific Reports2045-23222025-04-0115111610.1038/s41598-025-98901-4Exploring the anti-inflammatory activity of fupenzic acid using network pharmacology and experimental validationDjoudi Boukerouis0Irene Cuadrado1Nadjet Debbache Benaida2Ana Estévez-Braun3Beatriz de las Heras4Angel Amesty5Sonsoles Hortelano6Laboratoire de Biochimie Appliquée, Faculté des Sciences de la Nature et de la Vie, Université de BejaiaDepartamento de Farmacología, Farmacognosia y Botánica, Facultad de Farmacia , Universidad Complutense de Madrid (UCM)Laboratoire de Biochimie Appliquée, Faculté des Sciences de la Nature et de la Vie, Université de BejaiaDepartamento de Química Orgánica, Instituto Universitario de Bio-Orgánica Antonio González, Universidad de la LagunaDepartamento de Farmacología, Farmacognosia y Botánica, Facultad de Farmacia , Universidad Complutense de Madrid (UCM)Departamento de Química Orgánica, Instituto Universitario de Bio-Orgánica Antonio González, Universidad de la LagunaUnidad de Terapias Farmacológicas, Área de Genética Humana, Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos IIIAbstract Crataegus azarolus L. (Rosaceae), commonly known as Mediterranean hawthorn, has long been valued in Traditional Medicine for treating cardiovascular and inflammation-related diseases, including diabetes, cancer, and rheumatism. Pharmacological benefits of Crataegus azarolus L. are notably linked to its anti-inflammatory properties. Fupenzic acid, a pentacyclic triterpene isolated from its leaves, holds significant pharmacological potential that remains elusive. This study investigates the unexplored capacity of fupenzic acid as a promising anti-inflammatory agent. Using a multidisciplinary approach that integrates network pharmacology, molecular docking, in vitro assays, and predictive in silico analyses of drug-like properties, ADME, and toxicity, the mechanisms and properties of fupenzic acid have been elucidated. Network pharmacology analysis identified the potential targets for fupenzic acid, with enrichment analyses revealing key processes like inflammatory response, cytokine signaling, innate immune system, and MAPK cascade regulation. Transcription factors such as RELA, SP1, and NFKB1 were predicted to play crucial roles in its therapeutic effects. PPI network analysis underscored NF-κB as a central hub, linking these pathways to its anti-inflammatory effects. In vitro experiments demonstrated that fupenzic acid effectively suppressed inflammatory mediators like NOS-2 and COX-2, through the NF-κB pathway. Molecular docking further confirmed its favorable interaction with NF-κB, reinforcing its mechanism of action. Additionally, in silico ADMET profiling revealed favorable drug-like properties including pharmacokinetics and toxicity profiles, emphasizing its suitability as a drug candidate. This study represents a major step forward in understanding the therapeutic potential of fupenzic acid, establishing it as a distinctive and promising anti-inflammatory agent. The findings identified it as a pharmacological agent for clinical development targeting inflammation-driven diseases and also provide a foundation for future translational research.https://doi.org/10.1038/s41598-025-98901-4Fupenzic acidTriterpenoidsNetwork pharmacologyInflammationMolecular dockingIn Silico ADMET |
| spellingShingle | Djoudi Boukerouis Irene Cuadrado Nadjet Debbache Benaida Ana Estévez-Braun Beatriz de las Heras Angel Amesty Sonsoles Hortelano Exploring the anti-inflammatory activity of fupenzic acid using network pharmacology and experimental validation Scientific Reports Fupenzic acid Triterpenoids Network pharmacology Inflammation Molecular docking In Silico ADMET |
| title | Exploring the anti-inflammatory activity of fupenzic acid using network pharmacology and experimental validation |
| title_full | Exploring the anti-inflammatory activity of fupenzic acid using network pharmacology and experimental validation |
| title_fullStr | Exploring the anti-inflammatory activity of fupenzic acid using network pharmacology and experimental validation |
| title_full_unstemmed | Exploring the anti-inflammatory activity of fupenzic acid using network pharmacology and experimental validation |
| title_short | Exploring the anti-inflammatory activity of fupenzic acid using network pharmacology and experimental validation |
| title_sort | exploring the anti inflammatory activity of fupenzic acid using network pharmacology and experimental validation |
| topic | Fupenzic acid Triterpenoids Network pharmacology Inflammation Molecular docking In Silico ADMET |
| url | https://doi.org/10.1038/s41598-025-98901-4 |
| work_keys_str_mv | AT djoudiboukerouis exploringtheantiinflammatoryactivityoffupenzicacidusingnetworkpharmacologyandexperimentalvalidation AT irenecuadrado exploringtheantiinflammatoryactivityoffupenzicacidusingnetworkpharmacologyandexperimentalvalidation AT nadjetdebbachebenaida exploringtheantiinflammatoryactivityoffupenzicacidusingnetworkpharmacologyandexperimentalvalidation AT anaestevezbraun exploringtheantiinflammatoryactivityoffupenzicacidusingnetworkpharmacologyandexperimentalvalidation AT beatrizdelasheras exploringtheantiinflammatoryactivityoffupenzicacidusingnetworkpharmacologyandexperimentalvalidation AT angelamesty exploringtheantiinflammatoryactivityoffupenzicacidusingnetworkpharmacologyandexperimentalvalidation AT sonsoleshortelano exploringtheantiinflammatoryactivityoffupenzicacidusingnetworkpharmacologyandexperimentalvalidation |