# Caffeic acid phenethyl ester promotes palatal wound healing and enhances wound-associated macrophage CD68 expression

## TL;DR

Caffeic acid phenethyl ester (CAPE) speeds up healing of palatal wounds in mice and boosts CD68 expression in macrophages, reducing inflammation.

## Contribution

CAPE's effect on CD68 and inflammatory markers during palatal wound healing is newly demonstrated in this empirical study.

## Key findings

- CAPE-treated mice showed faster palatal wound closure compared to controls on days 3 and 5.
- CAPE increased CD68-positive cells and TGF-β1 while reducing TNF-α and iNOS expression.
- CAPE administration also caused significant weight gain in mice.

## Abstract

Palatal wounds may result in open lesions, which can lead to extended inflammation, discomfort, wound contraction, scar tissue development, interference with phonation or mastication, and disruption of maxillofacial growth. Flavonoids are known to possess the ability to diminish macrophage pro-inflammatory activity and to facilitate macrophage-mediated resolution of inflammation, thereby accelerating the healing process. Caffeic acid phenethyl ester (CAPE), the principal bioactive constituent of propolis, belongs to this family, and is known to diminish inflammatory cell count, accelerate wound contraction, and promote re-epithelialisation by decreasing lipid peroxidation and the production of reactive oxygen species. This study assesses the impact of CAPE on macrophage expression markers during palatal wound healing.

A total of 45 male BALB/c mice, aged 3 months, were allocated into control (saline), CAPE-treatment (CAPE-T), and CAPE-pretreatment (CAPE-PT) groups, and underwent palatal tissue excision at the mid-hard palate. CAPE was administered intraperitoneally at a dosage of 4 mg/kg of body weight. Clinical observation of palatal wound closure and liver were conducted by hematoxylin-eosin (HE) analysis. Immunohistochemical (IHC) examination of CD68 and TGF-β1 was conducted to assess the inflammatory markers during palatal wound closure.

On days 3 and 5, the CAPE-T and CAPE-PT groups showed faster wound healing than the control. CAPE also caused a significant weight gain in mice. IHC analysis revealed more CD68-positive cells and higher TGF-β1 levels, along with lower TNF-α and iNOS expression on day 5.

CAPE positively influences palatal wound healing by accelerating wound closure and modulating CD68, TGF-β1, TNF-α, and iNOS expression.