Najib Najib, Turhadi Turhadi, Fatchiyah Fatchiyah
Inflammation promotes insulin resistance by triggering the NF-κB signaling cascade, resulting in the production of pro-inflammatory cytokines like IL-6 and TNF-α. Moringa oleifera contains bioactive phytochemicals with reported anti-inflammatory potential, yet the molecular mechanisms underlying these effects remain unclear. This study aimed to identify novel drug targets for inflammation and to select a potent compound from M. oleifera with strong anti-inflammatory properties by suppressing the NF-κB cascade via in silico analysis. Phytochemicals of M. oleifera were screened for drug-likeness, toxicity, bioactivity, and membrane permeability. Target binding pockets in NF-κB, TNF-α, IL-6, and IKKβ were identified, followed by molecular docking and molecular dynamics (MD) simulations to evaluate binding affinity and complex stability. Four compounds met all screening criteria: quinic acid, kaempferol, 7-hydroxycoumarin, and p-coumaric acid. Kaempferol showed the strongest binding across all targets, with docking scores of-8.6,-8.5,-6.4, and-9.3 kcal/mol for NF-κB, TNF-α, IL-6, and IKKβ, respectively. Additionally, molecular dynamics analysis confirmed the stability of these interactions. These findings suggest that kaempferol can inhibit NF-κB signaling and its associated cytokines, offering a promising natural alternative for treating inflammation related to insulin resistance. © 2025 by the authors.
Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Malang, Indonesia; Research Center of Smart Molecule of Natural Genetics Resources, Brawijaya University, Malang, Indonesia
