Improved Wound Healing by Naringin Associated with MMP and the VEGF Pathway

This study aims to investigate the wound-healing effectiveness of the phenolic compound, naringin, both in vitro and in vivo. Male mice were shaved on their dorsal skin under isoflurane, a biopsy punch was made in four symmetrical circular resection windows (6 mm) to induce a wound. These excision w...

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Main Authors: Jia-Hau Yen, Wan-Ting Chio, Chia-Ju Chuang, Hsin-Ling Yang, Sheng-Teng Huang
Format: Article
Language:English
Published: MDPI AG 2022-03-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/27/5/1695
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author Jia-Hau Yen
Wan-Ting Chio
Chia-Ju Chuang
Hsin-Ling Yang
Sheng-Teng Huang
author_facet Jia-Hau Yen
Wan-Ting Chio
Chia-Ju Chuang
Hsin-Ling Yang
Sheng-Teng Huang
author_sort Jia-Hau Yen
collection DOAJ
description This study aims to investigate the wound-healing effectiveness of the phenolic compound, naringin, both in vitro and in vivo. Male mice were shaved on their dorsal skin under isoflurane, a biopsy punch was made in four symmetrical circular resection windows (6 mm) to induce a wound. These excision wounds were used to study the topical effects of naringin in terms of various biochemical, molecular, and histological parameters. We observed a significant recovery in the wound area. Increased levels of MMP-2, 9, 14, TIMP-2, VEGF-A, and VEGF-R1 were induced by naringin in the HaCaT cells. The time course experiments further revealed that levels of VEGF-A and B increased within 36 h; whereas levels of VEGF-C decreased. In line with this, VEGF-R3 levels, but not VEGF-R1 and 2 levels, increased soon after stimulation; although the increase subsided after 36 h. Additionally, naringin cream upregulated wound healing in vitro. The blockage of VEGF by Bevacizumab abolished the function of naringin cream on cell migration. Histological alterations in the wounded skin were restored by naringin cream, which accelerated wound healing via upregulated expression of growth factors (VEGF-A, B, and C and VEGF-R3), and thus increased MMP-2, 9, 14 expressions.
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spelling doaj.art-c80535deecb141dd90d66c6d6b04fae92023-11-23T23:28:21ZengMDPI AGMolecules1420-30492022-03-01275169510.3390/molecules27051695Improved Wound Healing by Naringin Associated with MMP and the VEGF PathwayJia-Hau Yen0Wan-Ting Chio1Chia-Ju Chuang2Hsin-Ling Yang3Sheng-Teng Huang4Cancer Research Center for Traditional Chinese Medicine, Department of Medical Research, China Medical University Hospital, Taichung 40402, TaiwanCancer Research Center for Traditional Chinese Medicine, Department of Medical Research, China Medical University Hospital, Taichung 40402, TaiwanCancer Research Center for Traditional Chinese Medicine, Department of Medical Research, China Medical University Hospital, Taichung 40402, TaiwanInstitute of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 40402, TaiwanCancer Research Center for Traditional Chinese Medicine, Department of Medical Research, China Medical University Hospital, Taichung 40402, TaiwanThis study aims to investigate the wound-healing effectiveness of the phenolic compound, naringin, both in vitro and in vivo. Male mice were shaved on their dorsal skin under isoflurane, a biopsy punch was made in four symmetrical circular resection windows (6 mm) to induce a wound. These excision wounds were used to study the topical effects of naringin in terms of various biochemical, molecular, and histological parameters. We observed a significant recovery in the wound area. Increased levels of MMP-2, 9, 14, TIMP-2, VEGF-A, and VEGF-R1 were induced by naringin in the HaCaT cells. The time course experiments further revealed that levels of VEGF-A and B increased within 36 h; whereas levels of VEGF-C decreased. In line with this, VEGF-R3 levels, but not VEGF-R1 and 2 levels, increased soon after stimulation; although the increase subsided after 36 h. Additionally, naringin cream upregulated wound healing in vitro. The blockage of VEGF by Bevacizumab abolished the function of naringin cream on cell migration. Histological alterations in the wounded skin were restored by naringin cream, which accelerated wound healing via upregulated expression of growth factors (VEGF-A, B, and C and VEGF-R3), and thus increased MMP-2, 9, 14 expressions.https://www.mdpi.com/1420-3049/27/5/1695naringinwound healingMMPsVEGFsVEGFRs
spellingShingle Jia-Hau Yen
Wan-Ting Chio
Chia-Ju Chuang
Hsin-Ling Yang
Sheng-Teng Huang
Improved Wound Healing by Naringin Associated with MMP and the VEGF Pathway
Molecules
naringin
wound healing
MMPs
VEGFs
VEGFRs
title Improved Wound Healing by Naringin Associated with MMP and the VEGF Pathway
title_full Improved Wound Healing by Naringin Associated with MMP and the VEGF Pathway
title_fullStr Improved Wound Healing by Naringin Associated with MMP and the VEGF Pathway
title_full_unstemmed Improved Wound Healing by Naringin Associated with MMP and the VEGF Pathway
title_short Improved Wound Healing by Naringin Associated with MMP and the VEGF Pathway
title_sort improved wound healing by naringin associated with mmp and the vegf pathway
topic naringin
wound healing
MMPs
VEGFs
VEGFRs
url https://www.mdpi.com/1420-3049/27/5/1695
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AT chiajuchuang improvedwoundhealingbynaringinassociatedwithmmpandthevegfpathway
AT hsinlingyang improvedwoundhealingbynaringinassociatedwithmmpandthevegfpathway
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