Protective Effects of Frankincense Oil on Wound Healing: Downregulating Caspase-3 Expression to Facilitate the Transition from the Inflammatory to Proliferative Phase

<b>Background/Objectives:</b> Wound healing is a complex process involving inflammation, oxidative stress, immune modulation, and tissue regeneration. Frankincense essential oil (FEO), derived from <i>Boswellia</i> species, is known for its anti-inflammatory, antioxidant, and therapeutic properties. This study investigates the protective effects of FEO in an excision wound model in rats, focusing on oxidative stress reduction, inflammatory cytokine modulation, and caspase-3 regulation. <b>Methods:</b> The chemical composition of FEO was analyzed using gas chromatography-mass spectrometry (GC-MS). Rats with excision wounds were treated with FEO, and its efficacy was assessed using biochemical and histological analyses. Caspase-3 expression, IL-1β, TNF-α, and CD68 levels were measured, along with oxidative stress markers. Wound contraction, epithelialization and collagen synthesis were also evaluated. Immunohistochemical and histopathological assessments were performed to analyze inflammatory infiltration and tissue remodeling. <b>Results:</b> FEO, rich in <i>alpha-phellandrene</i> (10.52%) and <i>limonene</i> (7.31%), significantly downregulated caspase-3, reducing apoptosis in the wound environment. It also lowered IL-1β and TNF-α levels, confirming anti-inflammatory effects. Additionally, FEO modulated CD68 expression, shifting the wound environment from inflammatory to healing. The oil antioxidant activity reduced oxidative stress, limiting caspase-3-mediated apoptosis and enhancing cell survival. FEO treatment accelerated wound contraction, improved epithelialization, and increased collagen synthesis. Histological analysis revealed reduced inflammatory infiltration and enhanced tissue remodeling. <b>Conclusions:</b> FEO integrates anti-inflammatory, antioxidant, and anti-apoptotic mechanisms to promote wound healing and tissue repair. Its ability to modulate caspase-3, IL-1β, TNF-α, CD68, and oxidative stress markers along with its major constituents such as <i>alpha-phellandrene</i> and <i>limonene</i> highlights its potential as a natural therapeutic agent for wound management and regenerative medicine.