Exploring the inflammatory pathway modulation of Phaleria macrocarpa: evidence from in vitro and in silico studies

Phaleria macrocarpa has been traditionally used in alternative medicine, yet its molecular anti-inflammatory mechanisms remain underexplored. This study investigates the anti-inflammatory potential of P. macrocarpa leaf ethanol extract in LPS-stimulated RAW 264.7 macrophages and elucidates its anti-...

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Main Authors: Assa’idatus Shofiah, Yuyun Ika Christina, Dinia Rizqi Dwijayanti, Aries Soewondo, Nashi Widodo, Muhammad Sasmito Djati
Format: Article
Language:English
Published: Pensoft Publishers 2025-08-01
Series:Pharmacia
Online Access:https://pharmacia.pensoft.net/article/153095/download/pdf/
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author Assa’idatus Shofiah
Yuyun Ika Christina
Dinia Rizqi Dwijayanti
Aries Soewondo
Nashi Widodo
Muhammad Sasmito Djati
author_facet Assa’idatus Shofiah
Yuyun Ika Christina
Dinia Rizqi Dwijayanti
Aries Soewondo
Nashi Widodo
Muhammad Sasmito Djati
author_sort Assa’idatus Shofiah
collection DOAJ
description Phaleria macrocarpa has been traditionally used in alternative medicine, yet its molecular anti-inflammatory mechanisms remain underexplored. This study investigates the anti-inflammatory potential of P. macrocarpa leaf ethanol extract in LPS-stimulated RAW 264.7 macrophages and elucidates its anti-inflammatory mechanisms through in silico studies. Cells were treated with the extract at 15, 30, and 60 µg/mL following LPS induction. Nitric oxide (NO) production and cell viability were assessed using the Griess and WST-1 assays, respectively. Flow cytometry quantified inducible nitric oxide synthase (iNOS) and interleukin (IL)-1β expression. Molecular docking and molecular dynamics simulations were performed to evaluate binding affinity and stability. The extract significantly reduced NO production, with an IC₅₀ value of 18.4 ± 3.1 µg/mL, while maintaining cell viability above 80%. Furthermore, treatment with P. macrocarpa extract significantly suppressed iNOS and IL-1β expression in a dose-dependent manner. Computational studies revealed strong interactions between extract-derived compounds and inflammation-related targets (AKT1, MMP9, PI3KCA, PI3KCG, and PTGS2), with stable molecular dynamics. These findings suggest that P. macrocarpa leaf extract exerts potent anti-inflammatory effects, highlighting its potential as a promising therapeutic candidate.
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institution Kabale University
issn 2603-557X
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publishDate 2025-08-01
publisher Pensoft Publishers
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series Pharmacia
spelling doaj-art-2e8a657c45bf4319b4075ce5253245752025-08-20T04:02:13ZengPensoft PublishersPharmacia2603-557X2025-08-017211410.3897/pharmacia.72.e153095153095Exploring the inflammatory pathway modulation of Phaleria macrocarpa: evidence from in vitro and in silico studiesAssa’idatus Shofiah0Yuyun Ika Christina1Dinia Rizqi Dwijayanti2Aries Soewondo3Nashi Widodo4Muhammad Sasmito Djati5Brawijaya UniversityBrawijaya UniversityBrawijaya UniversityBrawijaya UniversityBrawijaya UniversityBrawijaya UniversityPhaleria macrocarpa has been traditionally used in alternative medicine, yet its molecular anti-inflammatory mechanisms remain underexplored. This study investigates the anti-inflammatory potential of P. macrocarpa leaf ethanol extract in LPS-stimulated RAW 264.7 macrophages and elucidates its anti-inflammatory mechanisms through in silico studies. Cells were treated with the extract at 15, 30, and 60 µg/mL following LPS induction. Nitric oxide (NO) production and cell viability were assessed using the Griess and WST-1 assays, respectively. Flow cytometry quantified inducible nitric oxide synthase (iNOS) and interleukin (IL)-1β expression. Molecular docking and molecular dynamics simulations were performed to evaluate binding affinity and stability. The extract significantly reduced NO production, with an IC₅₀ value of 18.4 ± 3.1 µg/mL, while maintaining cell viability above 80%. Furthermore, treatment with P. macrocarpa extract significantly suppressed iNOS and IL-1β expression in a dose-dependent manner. Computational studies revealed strong interactions between extract-derived compounds and inflammation-related targets (AKT1, MMP9, PI3KCA, PI3KCG, and PTGS2), with stable molecular dynamics. These findings suggest that P. macrocarpa leaf extract exerts potent anti-inflammatory effects, highlighting its potential as a promising therapeutic candidate.https://pharmacia.pensoft.net/article/153095/download/pdf/
spellingShingle Assa’idatus Shofiah
Yuyun Ika Christina
Dinia Rizqi Dwijayanti
Aries Soewondo
Nashi Widodo
Muhammad Sasmito Djati
Exploring the inflammatory pathway modulation of Phaleria macrocarpa: evidence from in vitro and in silico studies
Pharmacia
title Exploring the inflammatory pathway modulation of Phaleria macrocarpa: evidence from in vitro and in silico studies
title_full Exploring the inflammatory pathway modulation of Phaleria macrocarpa: evidence from in vitro and in silico studies
title_fullStr Exploring the inflammatory pathway modulation of Phaleria macrocarpa: evidence from in vitro and in silico studies
title_full_unstemmed Exploring the inflammatory pathway modulation of Phaleria macrocarpa: evidence from in vitro and in silico studies
title_short Exploring the inflammatory pathway modulation of Phaleria macrocarpa: evidence from in vitro and in silico studies
title_sort exploring the inflammatory pathway modulation of phaleria macrocarpa evidence from in vitro and in silico studies
url https://pharmacia.pensoft.net/article/153095/download/pdf/
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