Assa’idatus Shofiah, Yuyun Ika Christina, Dinia Rizqi Dwijayanti, Aries Soewondo, Nashi Widodo, Muhammad Sasmito Djati
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. 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.
Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, East Java, Malang, 65145, Indonesia; Dewan Jamu Indonesia East Java Region, East Java, Malang, 65145, Indonesia; Innovation Center of Integrative Jamu and Eco-pharmaca, Brawijaya University, East Java, Malang, 65145, Indonesia; Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, East Java, Malang, 65145, Indonesia
