Huangbai Liniment Accelerated Wound Healing by Activating Nrf2 Signaling in Diabetes

As a serious complication of diabetes, nonhealing skin ulcer leads to high mortality and disability in diabetic patients. However, limited therapy is available in managing diabetic wounds. In this study, RNA-seq technology was used to systematically investigate the effect of Huangbai (HB) liniment,...

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Main Authors: Jingjing Zhang, Rui Zhou, Changpei Xiang, Qiang Jia, Hongwei Wu, Hongjun Yang
Format: Article
Language:English
Published: Hindawi Limited 2020-01-01
Series:Oxidative Medicine and Cellular Longevity
Online Access:http://dx.doi.org/10.1155/2020/4951820
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spelling doaj-4a2199e3c3104f06b4a8446bf102e8da2020-11-25T03:24:57ZengHindawi LimitedOxidative Medicine and Cellular Longevity1942-09001942-09942020-01-01202010.1155/2020/49518204951820Huangbai Liniment Accelerated Wound Healing by Activating Nrf2 Signaling in DiabetesJingjing Zhang0Rui Zhou1Changpei Xiang2Qiang Jia3Hongwei Wu4Hongjun Yang5Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaCollege of traditional Chinese Medicine, Yunnan University of Traditional Chinese Medicine, Kunming 650500, ChinaSchool of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaAs a serious complication of diabetes, nonhealing skin ulcer leads to high mortality and disability in diabetic patients. However, limited therapy is available in managing diabetic wounds. In this study, RNA-seq technology was used to systematically investigate the effect of Huangbai (HB) liniment, a traditional Chinese medicine, on the streptozotocin- (STZ-) induced diabetic wound. HB liniment significantly accelerated the wound closure and enhanced the generation of extracellular matrix in diabetic rats, and oxidative stress was identified to play a vital role in HB-mediated wound healing. Importantly, HB liniment activated nuclear factor erythroid-derived 2-like 2 (Nrf2) and its downstream antioxidant genes (e.g., genes involved in glutathione system, thioredoxin system, and GAPDH generation as well as other antioxidant genes), which inhibited oxidative damage and apoptosis. By associating drug targets of HB liniment with Nrf2 and its downstream genes, 54 components in HB liniment were screened out, and the majority was from Cortex Phellodendri and Forsythia suspensa. Additionally, HB liniment enhanced TGF-β1 and reduced MMP9 level, accelerating wound healing in diabetes. The in vitro experiment showed HB facilitated cell proliferation and inhibited oxidative damage in high glucose-induced HaCaT cells. Our findings provided the experimental evidence for the treatment of diabetic wound with HB, clarified the potential mechanism of HB, and improved our understanding of diabetic wound healing.http://dx.doi.org/10.1155/2020/4951820
collection DOAJ
language English
format Article
sources DOAJ
author Jingjing Zhang
Rui Zhou
Changpei Xiang
Qiang Jia
Hongwei Wu
Hongjun Yang
spellingShingle Jingjing Zhang
Rui Zhou
Changpei Xiang
Qiang Jia
Hongwei Wu
Hongjun Yang
Huangbai Liniment Accelerated Wound Healing by Activating Nrf2 Signaling in Diabetes
Oxidative Medicine and Cellular Longevity
author_facet Jingjing Zhang
Rui Zhou
Changpei Xiang
Qiang Jia
Hongwei Wu
Hongjun Yang
author_sort Jingjing Zhang
title Huangbai Liniment Accelerated Wound Healing by Activating Nrf2 Signaling in Diabetes
title_short Huangbai Liniment Accelerated Wound Healing by Activating Nrf2 Signaling in Diabetes
title_full Huangbai Liniment Accelerated Wound Healing by Activating Nrf2 Signaling in Diabetes
title_fullStr Huangbai Liniment Accelerated Wound Healing by Activating Nrf2 Signaling in Diabetes
title_full_unstemmed Huangbai Liniment Accelerated Wound Healing by Activating Nrf2 Signaling in Diabetes
title_sort huangbai liniment accelerated wound healing by activating nrf2 signaling in diabetes
publisher Hindawi Limited
series Oxidative Medicine and Cellular Longevity
issn 1942-0900
1942-0994
publishDate 2020-01-01
description As a serious complication of diabetes, nonhealing skin ulcer leads to high mortality and disability in diabetic patients. However, limited therapy is available in managing diabetic wounds. In this study, RNA-seq technology was used to systematically investigate the effect of Huangbai (HB) liniment, a traditional Chinese medicine, on the streptozotocin- (STZ-) induced diabetic wound. HB liniment significantly accelerated the wound closure and enhanced the generation of extracellular matrix in diabetic rats, and oxidative stress was identified to play a vital role in HB-mediated wound healing. Importantly, HB liniment activated nuclear factor erythroid-derived 2-like 2 (Nrf2) and its downstream antioxidant genes (e.g., genes involved in glutathione system, thioredoxin system, and GAPDH generation as well as other antioxidant genes), which inhibited oxidative damage and apoptosis. By associating drug targets of HB liniment with Nrf2 and its downstream genes, 54 components in HB liniment were screened out, and the majority was from Cortex Phellodendri and Forsythia suspensa. Additionally, HB liniment enhanced TGF-β1 and reduced MMP9 level, accelerating wound healing in diabetes. The in vitro experiment showed HB facilitated cell proliferation and inhibited oxidative damage in high glucose-induced HaCaT cells. Our findings provided the experimental evidence for the treatment of diabetic wound with HB, clarified the potential mechanism of HB, and improved our understanding of diabetic wound healing.
url http://dx.doi.org/10.1155/2020/4951820
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