Fatchiyah Fatchiyah, Feri E. Hermanto, Regina P. Virgirinia, Rista N. Rohmah, Lidwina F. Triprisila, Eko Suyanto, Katsuhiro Miyajima
Context: Senescence-associated secretory phenotype (SASP) marks the progression of cell senescence, where the cell produces a high level of inflammatory mediators and differentiation regulators. Targeting those mechanisms becomes a clear strategy to slow cellular senescence. Ferulic acid (FA) present in pigmented rice is well-known for its broad biological activity, including anti-inflammation and antioxidants. However, the role of FA as an anti-aging agent and its mechanism is limited. Aims: To evaluate the potential target of FA in modulating cellular aging using computational and in vitro analysis. Methods: Binding of FA to the target proteins analyzed by molecular docking analysis using PyRx and AutoDock Vina software. Lipid accumulation of mouse preadipocytes 3T3-L1 cells was analyzed using oil red O staining. Immunofluorescence staining was performed to analyze the level of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and nuclear factor-kappa B (NF-KB) proteins. Results: Several transcription factors and inflammatory mediators were used as targets for molecular docking, including CCAAT-enhancer-binding proteins-alpha (C/EBP-α), PPAR-γ, NF-KB, IkappaB kinase-beta (IKK-β), interleukin-6 (IL-6), IL-8, and their respective receptors. Although other protein targets have excellent binding energy and suitable FA-residues interactions, the molecular dynamics analysis showed that PPAR-γ was the most suitable target for FA in controlling the SASP process with high structural integrity and outperformed ligand-protein interaction stability. FA reduces the accumulation of lipids in differentiated preadipocyte cells. Importantly, FA treatment showed increases in the level of PPAR-γ while reducing the NF-KB proteins in vitro. Conclusions: Consequently, the FA could perform the anti-aging activity in preadipocyte cells by reducing SASP progression through activation of PPAR-γ signaling. © 2025 Journal of Pharmacy & Pharmacognosy Research.
Research Center of Smart Molecule of Natural Genetics Resource, Universitas Brawijaya, East Java, Malang, 65145, Indonesia; Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Brawijaya, East Java, Malang, 65145, Indonesia; Faculty of Animal Science, Universitas Brawijaya, East Java, Malang, 65145, Indonesia; Department of Oral Biology, Faculty of Dentistry, Universitas Brawijaya, East Java, Malang, 65145, Indonesia; Biosains Institute, Universitas Brawijaya, East Java, Malang, 65145, Indonesia; School of Chemistry, Institute of Science, Center for Biomolecular Structure, Function and Application, Suranaree University of Technology, Nakhon Ratchasima, 30000, Thailand; Laboratory of Food Safety Assessment Science, Department of Nutritional Science and Food Safety, Faculty of Applied Biosciences, Tokyo University of Agriculture Science, Tokyo, 183-8509, Japan
