Beneficial Effects of Caffeic Acid Phenethyl Ester on Wound Healing in a Diabetic Mouse: Role of VEGF and NO

Cutaneous wound healing is delayed in patients with diabetes. Caffeic acid phenethyl ester (CAPE) has been identified as an effective constituent of propolis with improved wound healing abilities via an oxidative stress decrease. However, its impact on wound healing in diabetic models and its underl...

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Main Authors: Sin-Hee Park, Soo-Young Song, Eun-Hye Park, Eunmin Kim, Gyu Chul Oh, Eun Ho Choo, Byung-Hee Hwang, Kiyuk Chang, Min-Ho Oak
Format: Article
Language:English
Published: MDPI AG 2022-02-01
Series:Applied Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-3417/12/5/2320
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author Sin-Hee Park
Soo-Young Song
Eun-Hye Park
Eunmin Kim
Gyu Chul Oh
Eun Ho Choo
Byung-Hee Hwang
Kiyuk Chang
Min-Ho Oak
author_facet Sin-Hee Park
Soo-Young Song
Eun-Hye Park
Eunmin Kim
Gyu Chul Oh
Eun Ho Choo
Byung-Hee Hwang
Kiyuk Chang
Min-Ho Oak
author_sort Sin-Hee Park
collection DOAJ
description Cutaneous wound healing is delayed in patients with diabetes. Caffeic acid phenethyl ester (CAPE) has been identified as an effective constituent of propolis with improved wound healing abilities via an oxidative stress decrease. However, its impact on wound healing in diabetic models and its underlying mechanisms remain unclear. Determining the vascular endothelial growth factor (VEGF) contents in a human vascular smooth muscle cell (VSMC)-conditioned medium was assessed using human VEGF immunoassay and vascular reactivity using porcine coronary artery rings. Later, C57BL/6 or db/db mice were anesthetized, after which a 6-mm biopsy punch was manipulated for perforation via the back skin. Subsequently, CAPE was applied to the wound and changed daily. Furthermore, the injury in each mouse was digitally photographed, and the wound area was quantified. We observed that CAPE increased VEGF levels in human VSMC-conditioned medium, improved endothelium-dependent nitric oxide (NO)-mediated vasorelaxation, inhibited U46619-induced vasoconstriction porcine coronary artery, and enhanced cutaneous wound healing in the diabetic mouse model. Hence, we propose that CAPE improves wound healing in diabetic mice, which is aided by increased VEGF and NO expression.
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spelling doaj.art-4763f0489989499e894867228462b7802023-11-23T22:38:54ZengMDPI AGApplied Sciences2076-34172022-02-01125232010.3390/app12052320Beneficial Effects of Caffeic Acid Phenethyl Ester on Wound Healing in a Diabetic Mouse: Role of VEGF and NOSin-Hee Park0Soo-Young Song1Eun-Hye Park2Eunmin Kim3Gyu Chul Oh4Eun Ho Choo5Byung-Hee Hwang6Kiyuk Chang7Min-Ho Oak8Cardiovascular Research Institute for Intractable Disease, College of Medicine, The Catholic University of Korea, Seoul 06591, KoreaCollege of Pharmacy, Mokpo National University, Muan-gun 58554, KoreaCardiovascular Research Institute for Intractable Disease, College of Medicine, The Catholic University of Korea, Seoul 06591, KoreaCardiovascular Research Institute for Intractable Disease, College of Medicine, The Catholic University of Korea, Seoul 06591, KoreaCardiovascular Research Institute for Intractable Disease, College of Medicine, The Catholic University of Korea, Seoul 06591, KoreaCardiovascular Research Institute for Intractable Disease, College of Medicine, The Catholic University of Korea, Seoul 06591, KoreaCardiovascular Research Institute for Intractable Disease, College of Medicine, The Catholic University of Korea, Seoul 06591, KoreaCardiovascular Research Institute for Intractable Disease, College of Medicine, The Catholic University of Korea, Seoul 06591, KoreaCollege of Pharmacy, Mokpo National University, Muan-gun 58554, KoreaCutaneous wound healing is delayed in patients with diabetes. Caffeic acid phenethyl ester (CAPE) has been identified as an effective constituent of propolis with improved wound healing abilities via an oxidative stress decrease. However, its impact on wound healing in diabetic models and its underlying mechanisms remain unclear. Determining the vascular endothelial growth factor (VEGF) contents in a human vascular smooth muscle cell (VSMC)-conditioned medium was assessed using human VEGF immunoassay and vascular reactivity using porcine coronary artery rings. Later, C57BL/6 or db/db mice were anesthetized, after which a 6-mm biopsy punch was manipulated for perforation via the back skin. Subsequently, CAPE was applied to the wound and changed daily. Furthermore, the injury in each mouse was digitally photographed, and the wound area was quantified. We observed that CAPE increased VEGF levels in human VSMC-conditioned medium, improved endothelium-dependent nitric oxide (NO)-mediated vasorelaxation, inhibited U46619-induced vasoconstriction porcine coronary artery, and enhanced cutaneous wound healing in the diabetic mouse model. Hence, we propose that CAPE improves wound healing in diabetic mice, which is aided by increased VEGF and NO expression.https://www.mdpi.com/2076-3417/12/5/2320caffeic acid phenethyl esterwound healingvascular endothelial growth factornitric oxide
spellingShingle Sin-Hee Park
Soo-Young Song
Eun-Hye Park
Eunmin Kim
Gyu Chul Oh
Eun Ho Choo
Byung-Hee Hwang
Kiyuk Chang
Min-Ho Oak
Beneficial Effects of Caffeic Acid Phenethyl Ester on Wound Healing in a Diabetic Mouse: Role of VEGF and NO
Applied Sciences
caffeic acid phenethyl ester
wound healing
vascular endothelial growth factor
nitric oxide
title Beneficial Effects of Caffeic Acid Phenethyl Ester on Wound Healing in a Diabetic Mouse: Role of VEGF and NO
title_full Beneficial Effects of Caffeic Acid Phenethyl Ester on Wound Healing in a Diabetic Mouse: Role of VEGF and NO
title_fullStr Beneficial Effects of Caffeic Acid Phenethyl Ester on Wound Healing in a Diabetic Mouse: Role of VEGF and NO
title_full_unstemmed Beneficial Effects of Caffeic Acid Phenethyl Ester on Wound Healing in a Diabetic Mouse: Role of VEGF and NO
title_short Beneficial Effects of Caffeic Acid Phenethyl Ester on Wound Healing in a Diabetic Mouse: Role of VEGF and NO
title_sort beneficial effects of caffeic acid phenethyl ester on wound healing in a diabetic mouse role of vegf and no
topic caffeic acid phenethyl ester
wound healing
vascular endothelial growth factor
nitric oxide
url https://www.mdpi.com/2076-3417/12/5/2320
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