Topical anti-inflammatory activity of palmitoleic acid improves wound healing

Abstract

This study investigated the effects of palmitoleic acid on different phases of the healing process. Macroscopic analyses were performed on wounds in rats with or without palmitoleic acid treatment, and the results showed that palmitoleic acid directly hastened wound closure. The topical treatment of wounds with palmitoleic acid resulted in smaller wounds than those observed in the control group. The anti-inflammatory activity of palmitoleic acid may be responsible for healing, especially in the stages of granulation tissue formation and remodelling. Palmitoleic acid modified TNF-α, IL-1β, IL-6, CINC-2α/β, MIP-3α and VEGF-α profiles at the wound site 24, 48, 120, 216 and 288 hours post-wounding. Assays assessing neutrophil migration and exudate formation in sterile inflammatory air pouches revealed that palmitoleic acid had potent anti-inflammatory activity, inhibiting the LPS-induced release of TNF-α (73.14%, p≤0.05), IL-1β (66.19%, p≤0.001), IL-6 (75.19%, p≤0.001), MIP-3α (70.38%, p≤0.05), and l-selectin (16%, p≤0.05). Palmitoleic acid also inhibited LPS-stimulated neutrophil migration. We concluded that palmitoleic acid accelerates wound healing via an anti-inflammatory effect.

Fig 1. Wound closure velocity.

Macroscopic wound closure in the control rats (A) and the rats treated daily with palmitoleic acid (B). Representative photos and wound area values recorded over a 12-day period. (C) Wound closure velocity (mm²/day) and (D) ratios of integrated wound closure area with or without palmitoleic treatment. Values are expressed as the mean±SEM of at least 10 animals per group. *p≤0.05 versus control, as indicated by analysis of variance (ANOVA) and post hoc Tukey’s test.

Fig 2. Neutrophils migration.

Neutrophil influx into air pouches after palmitoleic acid (100 mM) injection. LPS (5 μg/mL) was used as a positive control. Values are presented as the means±SEM of eight animals per group. **p<0.01 for comparisons between treatments with fatty acids and control, as indicated.

Fig 3. Air pouch cytokines release.

Cytokine release into air pouches after palmitoleic acid (100 mM) injection. LPS (5 μg/mL) was used as a positive control. Values are presented as the means±SEM of eight animals per group. *p<0.05, **p<0.01 and ***p<0.001 for comparisons between treatments with fatty acids and control, as indicated by ANOVA and Dunnett’s test.

Fig 4. Cytokines concentration in wound.

Kinetic profiles of cytokine concentrations in the control (PBS) and treated rats (PALM) measured before (0), 4 hours (4), 24 hours (24), 48 hours (48), 72 hours (72) and 120 hours (120) after wound induction. Values are presented as the mean±SE of at least 8 animals per group.