TY - JOUR
T1 - Exploring the inflammatory pathway modulation of Phaleria macrocarpa
T2 - Evidence from in vitro and in silico studies
AU - Shofiah, Assa’idatus
AU - Christina, Yuyun Ika
AU - Dwijayanti, Dinia Rizqi
AU - Soewondo, Aries
AU - Widodo, Nashi
AU - Djati, Muhammad Sasmito
N1 - Publisher Copyright:
Copyright Shofiah A et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2025
Y1 - 2025
N2 - 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.
AB - 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.
KW - AKT-1
KW - Phaleria macrocarpa
KW - iNOS
KW - inflammation
KW - nitric oxide
UR - https://www.scopus.com/pages/publications/105016698691
U2 - 10.3897/pharmacia.72.e153095
DO - 10.3897/pharmacia.72.e153095
M3 - Article
AN - SCOPUS:105016698691
SN - 0428-0296
VL - 72
JO - Pharmacia
JF - Pharmacia
ER -