Huiyang Shengji decoction promotes wound healing in diabetic mice by activating the EGFR/PI3K/ATK pathway

Abstract Background Common chronic wounds include diabetic ulcers, venous ulcers, and pressure ulcers. The traditional Chinese medicine Huiyang Shengji decoction (HYSJD) has been shown to promote the healing of diabetic chronic wounds, however, its pharmacological mechanism is still unclear. Purpose...

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Autores principales:	Qingwu Liu, Jinchao Zhang, Xuyang Han, Jia Chen, Yating Zhai, Yan Lin, Huike Ma, Fang Feng, Xiujuan He, Ping Li
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Wound healing Traditional Chinese medicine Huiyang Shengji decoction (HYSJD) Other systems of medicine RZ201-999
Acceso en línea:	https://doaj.org/article/ca86aa77935d46399496ef467e90b526
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spelling	oai:doaj.org-article:ca86aa77935d46399496ef467e90b5262021-11-07T12:13:02ZHuiyang Shengji decoction promotes wound healing in diabetic mice by activating the EGFR/PI3K/ATK pathway10.1186/s13020-021-00497-01749-8546https://doaj.org/article/ca86aa77935d46399496ef467e90b5262021-11-01T00:00:00Zhttps://doi.org/10.1186/s13020-021-00497-0https://doaj.org/toc/1749-8546Abstract Background Common chronic wounds include diabetic ulcers, venous ulcers, and pressure ulcers. The traditional Chinese medicine Huiyang Shengji decoction (HYSJD) has been shown to promote the healing of diabetic chronic wounds, however, its pharmacological mechanism is still unclear. Purpose This study aimed to determine the mechanism of HYSJD in promoting the healing of diabetic chronic skin ulcers. Methods Ultra-performance liquid chromatography was combined with tandem mass spectrometry (UPLC-MS/MS) to analyze the main components of HYSJD and the absorbed components in mouse serum at 30 min after oral administration of HYSJD. db/db mouse models for chronic skin ulcers were constructed by full-thickness skin resection. Wound tissues at day 7 post wound formation were used to perform microarray analysis of growth factors and chemokine expression. GO and KEGG enrichment analysis was performed on differentially expressed proteins. ELISA assays were used to measure differential expressed cytokines in the serum and Western blot analysis was used to determine the expression levels of related pathway proteins in the skin wounds. Results UPLC-MS/MS analysis showed that the main chemical components of HYSJD were flavonoids, terpenes, alkaloids, phenylpropanoids, and carbohydrates. At 30 min after oral administration of HYSJD, five absorbed components were detected in the serum, these included formononetin, calycosin, hypaconitine, calycosin-7-glucoside, and sinapic acid. HYSJD was found to increase the wound healing rate in chronic skin ulcers in db/db mice at days 3, 7, and 14 post wound formation, and promote the proliferation of epidermal cells. Two proteins that were differentially expressed between the different groups, i.e., IGF-1 and EGFR, were further validated. Serum ELISA assays showed that serum EGFR in the HYSJD treatment group was significantly increased. KEGG pathway analysis suggested that the PI3K/AKT pathway involved in HYSJD promoting the proliferation of epidermal cells in chronic wounds in db/db mice. Experimental verification showed that HYSJD activated the PI3K/AKT signaling pathway in mouse wound skin. Conclusion HYSJD promotes the proliferation of epidermal cells in chronic diabetic wounds by increasing EGFR expression in the wounds and activating the PI3K/AKT signaling pathway. Our study provides an experimental basis for the pharmacological mechanism of HYSJD.Qingwu LiuJinchao ZhangXuyang HanJia ChenYating ZhaiYan LinHuike MaFang FengXiujuan HePing LiBMCarticleWound healingTraditional Chinese medicineHuiyang Shengji decoction (HYSJD)Other systems of medicineRZ201-999ENChinese Medicine, Vol 16, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Wound healing Traditional Chinese medicine Huiyang Shengji decoction (HYSJD) Other systems of medicine RZ201-999
spellingShingle	Wound healing Traditional Chinese medicine Huiyang Shengji decoction (HYSJD) Other systems of medicine RZ201-999 Qingwu Liu Jinchao Zhang Xuyang Han Jia Chen Yating Zhai Yan Lin Huike Ma Fang Feng Xiujuan He Ping Li Huiyang Shengji decoction promotes wound healing in diabetic mice by activating the EGFR/PI3K/ATK pathway
description	Abstract Background Common chronic wounds include diabetic ulcers, venous ulcers, and pressure ulcers. The traditional Chinese medicine Huiyang Shengji decoction (HYSJD) has been shown to promote the healing of diabetic chronic wounds, however, its pharmacological mechanism is still unclear. Purpose This study aimed to determine the mechanism of HYSJD in promoting the healing of diabetic chronic skin ulcers. Methods Ultra-performance liquid chromatography was combined with tandem mass spectrometry (UPLC-MS/MS) to analyze the main components of HYSJD and the absorbed components in mouse serum at 30 min after oral administration of HYSJD. db/db mouse models for chronic skin ulcers were constructed by full-thickness skin resection. Wound tissues at day 7 post wound formation were used to perform microarray analysis of growth factors and chemokine expression. GO and KEGG enrichment analysis was performed on differentially expressed proteins. ELISA assays were used to measure differential expressed cytokines in the serum and Western blot analysis was used to determine the expression levels of related pathway proteins in the skin wounds. Results UPLC-MS/MS analysis showed that the main chemical components of HYSJD were flavonoids, terpenes, alkaloids, phenylpropanoids, and carbohydrates. At 30 min after oral administration of HYSJD, five absorbed components were detected in the serum, these included formononetin, calycosin, hypaconitine, calycosin-7-glucoside, and sinapic acid. HYSJD was found to increase the wound healing rate in chronic skin ulcers in db/db mice at days 3, 7, and 14 post wound formation, and promote the proliferation of epidermal cells. Two proteins that were differentially expressed between the different groups, i.e., IGF-1 and EGFR, were further validated. Serum ELISA assays showed that serum EGFR in the HYSJD treatment group was significantly increased. KEGG pathway analysis suggested that the PI3K/AKT pathway involved in HYSJD promoting the proliferation of epidermal cells in chronic wounds in db/db mice. Experimental verification showed that HYSJD activated the PI3K/AKT signaling pathway in mouse wound skin. Conclusion HYSJD promotes the proliferation of epidermal cells in chronic diabetic wounds by increasing EGFR expression in the wounds and activating the PI3K/AKT signaling pathway. Our study provides an experimental basis for the pharmacological mechanism of HYSJD.
format	article
author	Qingwu Liu Jinchao Zhang Xuyang Han Jia Chen Yating Zhai Yan Lin Huike Ma Fang Feng Xiujuan He Ping Li
author_facet	Qingwu Liu Jinchao Zhang Xuyang Han Jia Chen Yating Zhai Yan Lin Huike Ma Fang Feng Xiujuan He Ping Li
author_sort	Qingwu Liu
title	Huiyang Shengji decoction promotes wound healing in diabetic mice by activating the EGFR/PI3K/ATK pathway
title_short	Huiyang Shengji decoction promotes wound healing in diabetic mice by activating the EGFR/PI3K/ATK pathway
title_full	Huiyang Shengji decoction promotes wound healing in diabetic mice by activating the EGFR/PI3K/ATK pathway
title_fullStr	Huiyang Shengji decoction promotes wound healing in diabetic mice by activating the EGFR/PI3K/ATK pathway
title_full_unstemmed	Huiyang Shengji decoction promotes wound healing in diabetic mice by activating the EGFR/PI3K/ATK pathway
title_sort	huiyang shengji decoction promotes wound healing in diabetic mice by activating the egfr/pi3k/atk pathway
publisher	BMC
publishDate	2021
url	https://doaj.org/article/ca86aa77935d46399496ef467e90b526
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Huiyang Shengji decoction promotes wound healing in diabetic mice by activating the EGFR/PI3K/ATK pathway

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