Topical Application of Sepia Ink Extract-Loaded Phytosome on Mouse Skin Injury Accelerates Wound Healing: A Histopathological,Immunohistochemical,and Biochemical Study

Sepia officinalis ink contains bioactive secondary metabolites abundant in melanin granules, has extensive medicinal properties and is commonly utilized in the prevention of different diseases. This research examined the topical wound healing efficacy of sepia ink extract (SIE) and SIE- Nanoparticle-loaded phytosome (SIE-NP) in a murine model of excisional wound healing. Mice were divided into five groups, all groups were anesthetized, and excisional skin wounds were established using a biopsy punch, except the control group. Both SIE and SIE-NP significantly improved the wound healing rate; nevertheless, the effect of SIE-NP was more pronounced. Treatment with SIE and SIE-NP accelerated the wound healing process by mitigating oxidative stress, evidenced by a reduction in malondialdehyde levels and an enhancement in antioxidants levels, including catalase and glutathione. SIE and SIE-NP attenuated oxidative stress-induced DNA fragmentation in wound tissue. Additionally, they reduced the levels of inflammatory markers, such as TNF-α and IL-6, myeloperoxidase activity, and the infiltration of inflammatory cells in the skin tissue. Furthermore, SIE and SIE-NP reduced histopathological abnormalities and concentration of fragmented DNA and elevated nitric oxide levels and collagen content. Moreover, SIE and SIE-NP decreased apoptosis by lowering caspase 3 expression. The data indicate that SIE and SIE-NP expedited wound healing via their antioxidant, anti-inflammatory, and anti-apoptotic characteristics.