Wound healing potential of naringin ointment formulation via regulating the expression of inflammatory, apoptotic and growth mediators in experimental rats

Context: Wound healing is a consequence of a complex process involving inflammatory, proliferative, and remodeling phases. Naringin, a flavanone glycoside, is associated with modulation of various oxido-inflammatory and growth factors. Aim: The aim of this study is to evaluate the wound-healing activity of naringin ointment formulation (NOF) on experimental wound models. Materials and methods: A soft paraffin-based cream containing 1, 2, and 4% (w/w) naringin was formulated and evaluated for physicochemical characters. Excision wounds and incisions wounds were used to study the topical effect of NOF for 20 d (once a day) on various biochemical, molecular, and histological parameters. Results: NOF (2 and 4%, w/w) treatment showed a significant decrease (p<0.05) in wound area and epithelization period whereas the rate of wound contraction increased significantly (p<0.05). The altered levels of oxido-nitrosative stress (SOD, GSH, MDA, MPO, and NO) were significantly (p<0.05) restored by NOF. Treatment produced a significant increase (p<0.05) in tensile strength, hydroxyproline content, and protein content. TNF-alpha, IL-1, IL-6, IL-8, NF-kappa B, smad-7, and Bax mRNA expression were significantly down-regulated (p<0.05) by NOF, whereas polymerase gamma (pol-gamma), smad-3, VEGF and TGF-beta, and collagen-1 mRNA expressions were significantly up-regulated (p<0.05) by NOF. Histological alterations in wound skin were also restored by NOF. Conclusion: NOF exerts wound healing potential via down-regulated expression of inflammatory (NF-kappa B, TNF-alpha, and ILs), apoptotic (pol-gamma and Bax), and up-regulated growth factor (VEGF and TGF-beta) expression, thus modulating collagen-1 expression to induce angiogenesis leading to wound healing.