Editya Fukata, Mohammad Saifur Rohman, Aulanniam, Husnul Khotimah, Nik Ahmad Nizam Nik Malek, Agustina Tri Endharti
Hyperglycemia disrupts wound healing in diabetes partly by promoting fibroblast apoptosis. This study aimed to evaluate whether cinnamaldehyde-chitosan nanoparticles (CCNPs) can inhibit high-glucose-induced fibroblasts apoptosis, and to determine whether this effect involves modulation of the PI3K/AKT pathway. CCNPs were synthesized using a modified ionic-gelation method and characterized by Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM). Murine embryonic fibroblasts cell line (NIH-3T3) were allocated to 6 groups: 2 control groups-normal glucose (NG, 5.5 mM glucose) and high glucose (HG, 30 mM glucose)-and 4 treatment groups that were pretreated with metformin (50 µM) or CCNPs (12.5, 25 and 50 µM) prior to 24 h of HG exposure. After 24 h of treatment, PI3K and phosphorylated-AKT levels in the cell lysates were quantified using ELISA, and fibroblasts apoptosis was assessed and quantified by Annexin V-PI flow cytometry. Synthesized CCNPs exhibited spherical morphology with an average diameter of 214.8 ± 54.0 nm, a polydispersity index (PDI) of 0.419, and a ζ-potential of +66.2 mV. High glucose exposure significantly increased the proportion of late apoptotic cells and reduced PI3K and p-AKT expression, compared with NG group (p < 0.05). Meanwhile, CCNPs at all tested concentrations significantly reduced late apoptotic cell percentages in a concentration-dependent manner, whereas only CCNPs at 50 µM significantly restored both PI3K and p-AKT levels. These findings suggest that CCNPs mitigate high-glucose-induced fibroblast apoptosis and is likely associated with the activation of PI3K/AKT pathway. This study provides preliminary in vitro evidence supporting a potential fibroblast-protective role of CCNPs under hyperglycemic conditions. Limitations of this study include the short-term in-vitro design and the absence of a direct comparison between CCNPs versus cinnamaldehyde only. Future studies should incorporate longer exposure durations, pathway-specific inhibitor, and in-vivo validation. © 2026, Walailak University. All rights reserved.
Doctoral Program in Medical Science, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia; Department of Medicine, Faculty of Medicine, Universitas Negeri Malang, Malang, Indonesia; Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Brawijaya-Saiful Anwar General Hospital, Malang, Indonesia; Cardiovascular Research Centre, Universitas Brawijaya, Malang, Indonesia; Department of Chemistry, Faculty of Sciences, Universitas Brawijaya, Malang, Indonesia; Department of Pharmacology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia; Universiti Teknologi Malaysia, Centre for Sustainable Nanomaterials (CSNano), Universiti Teknologi Malaysia, Johor Bahru, Malaysia; Department of Parasitology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia; Biomedical Central Laboratory, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia
