NF-κB and COX-2 repression with topical application of hesperidin and naringin hydrogels augments repair and regeneration of deep dermal wounds

Abstract

Introduction: Wound injury is common and causes serious complications if not treated properly. The moist dressing heals wounds faster than other dressings. Therefore, we sought to study the effect of hesperidin/naringin hydrogel wound dressing or their combinations on the deep dermal wounds in mice.

Methods: A rectangular full thickness skin flap of 2.5 × 1.5 cm was excised from depilated mice dorsum and the wound was fully covered with 5% hesperidin/5% naringin hydrogel or both in the ratio of 1:1, 2:1, or 1:2, respectively once daily until complete healing of the wound. Data were collected on wound contraction, mean wound healing time, collagen, DNA, and nitric oxide syntheses, glutathione concentration, superoxide dismutase activity, and lipid peroxidation throughout healing. Expression of NF-κB and COX-2 were also estimated in the regenerating granulation tissue using Western blot.

Findings: Dressing of wounds with 5% hesperidin hydrogel led to a higher and early wound contraction and significantly reduced mean wound healing time by 5.7 days than 5% naringin or combination of hesperidin and naringin hydrogels in the ratio of 1:1, 2:1, or 1:2. Hesperidin hydrogel wound dressing caused higher collagen and DNA syntheses than other groups at all times after injury. Glutathione concentration and superoxide dismutase activity increased followed by a decline in lipid peroxidation in regenerating wounds after hesperidin/naringin hydrogel application and a maximum effect was observed for hesperidin alone. The hesperidin/naringin hydrogel suppressed NF-κB and COX-2 expression on days 6 and 12.

Conclusions: Application of 5% hesperidin hydrogel was more effective than 5% naringin or combination of hesperidin and naringin gels (1:1, 2:1 or 1:2) indicated by a greater wound contraction, reduced mean wound healing time, elevated collagen and DNA syntheses, rise in glutathione concentration, and superoxide dismutase activity followed by reduced lipid peroxidation, and NF-κB, and COX-2 expression.

Keywords: Collagen; DNA; Lipid peroxidation; Mice; NF-κB; Wound healing.