Effect of Apigenin Nanoemulgel on Inflammatory Phase Acceleration in Burn Wound Healing: In Silico and In Vivo Studies

Abstract

Background: Burns are destructive wounds that trigger inflammation, neuropathic pain, and the risk of infection. The nuclear factor kappa B (NF-κB) signalling pathway plays an important role in regulating inflammation and tissue regeneration. Apigenin, the main flavonoid in celery (Apium graveolens), has anti-inflammatory, antioxidant, and angiogenic effects, but its bioavailability is low due to its lipophilic nature. Objectives: We analyzed the effects of apigenin-loaded nanoemulgel (NA) administration in modulating inflammation and accelerating burn wound healing in silico and in vivo. Methods: In silico analysis was conducted using molecular docking against NF-κB, MMP-1, and COX-2. In vivo testing involved 12 rats, each with three burns (±100 °C, 5 seconds), divided into three treatment groups: Apigenin-loaded NA, positive control (bioplacenton®), and negative control (placebo). Macroscopic and histopathological evaluations were conducted on days 3, 7, 14, and 21. Histopathological parameters included re-epithelialization, neutrophil count, lymphocyte count, and collagen density. Results: In vivo administration of apigenin-loaded NA accelerated the closure of macroscopic wounds, reduced the number of neutrophils, and significantly increased collagen density (P<0.05). There were no significant differences in lymphocyte counts and increased re-epithelialization, as determined by statistical testing. In silico validation of apigenin showed stronger binding affinity to MMP-1 and COX-2 than to native ligands, while a lower affinity was observed for NF-κB. Conclusion: Apigenin-loaded NA is an effective topical agent in accelerating the initial inflammatory phase and promoting wound healing in burn injuries.