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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Bibliographic Details
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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Summary: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.
ISSN:2603-557X