Intravenous curcumin efficacy on healing and scar formation in rabbit ear wounds under nonischemic, ischemic, and ischemia–reperfusion conditions

Abstract

Curcumin, a spice found in turmeric, is widely used in alternative medicine for its purported anti-inflammatory and antioxidant activities. The goal of this study was to test the curcumin efficacy on rabbit ear wounds under nonischemic, ischemic, and ischemia-reperfusion conditions. Previously described models were utilized in 58 New Zealand White rabbits. Immediately before wounding, rabbits were given intravenous crude or pure curcumin (6 μg/kg, 30 μg/kg, or 60 μg/kg) dissolved in 1% ethanol. Specimens were collected at 7-8 days to evaluate the effects on wound healing and at 28 days to evaluate the effects on hypertrophic scarring. Student's t test was applied to screen difference between any treatment and control group, whereas analysis of variance was applied to further analyze for all treatment groups in aggregate in some specific experiments. Treatment with crude curcumin suggested accelerated wound healing that reached significance for reepithelialization in lower and medium doses and granulation tissue formation in lower dose. Purified curcumin became available and was used for all later experiments. Treatment with pure curcumin suggested accelerated wound healing that reached significance for reepithelialization in lower and medium doses and granulation tissue formation in lower dose. Treatment with pure curcumin significantly promoted nonischemic wound healing in a dose-response fashion compared with controls as judged by increased reepithelialization and granulation tissue formation. Improved wound healing was associated with significant decreases in pro-inflammatory cytokines interleukin (IL)-1 and IL-6 as well as the chemokine IL-8. Curcumin also significantly reduced hypertrophic scarring. The effects of curcumin were examined under conditions of impaired healing including ischemic and ischemia-reperfusion wound healing, and beneficial effects were also seen, although the dose response was less clear. Systemically administrated pure curcumin significantly promotes nonischemic wound healing and reduces hypertrophic scarring. Improvements in wound healing were associated with decreased inflammatory markers in wounds. Further study is needed to optimize dosing in ischemic and ischemia-reperfusion wound healing. In aggregate, the studies strongly support the systemic administration of curcumin to improve wound healing.

Effect of dual‐drug‐releasing micelle–hydrogel composite on wound healing in vivo in full‐thickness excision wound rat model

“…) indicated that the initial migration of cells was faster in the HC and LC groups than in the blank and control groups. This might be a consequence of the constant release of curcumin in the HC and LC groups, in agreement with published observations that curcumin considerably improves granulation in non‐ischemic wounds …”

“…This might be a consequence of the constant release of curcumin in the HC and LC groups, in agreement with published observations that curcumin considerably improves granulation in non-ischemic wounds. 60 A series of important events takes place at the edge of the wound, accompanying granulation. Epidermal cells in the direct vicinity of the edge of the wound begin to thicken within the first 24-48 h post injury.…”

Local Application of Statins Significantly Reduced Hypertrophic Scarring in a Rabbit Ear Model

“…33 Briefly, 4 or 6 full-thickness dermal punches 7 mm in diameter were made on the ventral surface of the ear down to but not including the perichondrium. The cartilage was scored around the circumference of the wound to allow for histomorphometric analysis.…”

“…Several histomorphometric measurements were determined using a digital image analysis system (NIS-Elements Basic Research, Nikon Corporation, Kanagawa, Japan) at 2× and 10× magnification as previously described. 33 Each parameter was measured in a blind manner. Scar elevation index (SEI) was calculated to quantify the extent of hypertrophic scarring in the scarring model.…”

Biomaterials and tissue engineering for scar management in wound care

“…Curcumin was found to suppress TGF-β1/SMAD pathway and extra cellular matrix (ECM) production in primary keloid fibroblasts and reduce pro-inflammatory cytokines, interleukins (IL-1β, IL-6, and IL-8), which directly decrease hypertrophic scarring [20]. …”