Paeoniflorin Suppresses TBHP-Induced Oxidative Stress and Apoptosis in Human Umbilical Vein Endothelial Cells via the Nrf2/HO-1 Signaling Pathway and Improves Skin Flap Survival

Random-pattern skin flap is a vital technique frequently applied in reconstruction surgeries for its convenience and effectiveness in solving skin defects. However, ischemic necrosis, especially in the distal areas of the flap, still needs extra attention after surgery. Earlier evidence has suggeste...

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Autores principales:	Jingtao Jiang, Chengji Dong, Liang Zhai, Junsheng Lou, Jie Jin, Sheng Cheng, Zhuliu Chen, Xiaoshan Guo, Damu Lin, Jian Ding, Weiyang Gao
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	paeoniflorin random skin flap oxidative stress apoptosis angiogenesis Nrf2/HO-1 signaling pathway Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/6fe4cfca01da4411b1d62807b690bc23
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spelling	oai:doaj.org-article:6fe4cfca01da4411b1d62807b690bc232021-11-04T09:32:30ZPaeoniflorin Suppresses TBHP-Induced Oxidative Stress and Apoptosis in Human Umbilical Vein Endothelial Cells via the Nrf2/HO-1 Signaling Pathway and Improves Skin Flap Survival1663-981210.3389/fphar.2021.735530https://doaj.org/article/6fe4cfca01da4411b1d62807b690bc232021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.735530/fullhttps://doaj.org/toc/1663-9812Random-pattern skin flap is a vital technique frequently applied in reconstruction surgeries for its convenience and effectiveness in solving skin defects. However, ischemic necrosis, especially in the distal areas of the flap, still needs extra attention after surgery. Earlier evidence has suggested that paeoniflorin (PF) could stimulate angiogenesis and suppress ischemic cardiovascular disease. However, few studies have focused on the role of PF in flap survival. In this study, we have demonstrated that the human umbilical vein endothelial cells (HUVECs) treated with PF can alleviate tert-butyl hydroperoxide (TBHP)-stimulated cellular dysfunction and apoptosis. To better evaluate, HUVECs’ physiology, cell tube formation, migration, and adhesion were assessed. Mechanistically, PF protects HUVECs against apoptosis via stimulating the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway. PF also downregulates mitochondrial ROS production to reduce excessive intracellular ROS production induced by TBHP and restore TBHP-induced mitochondrial depolarization. As a result, silencing Nrf2 partially abolishes the protective effect of PF exposure on HUVECs. In in vivo experiments, the oral administration of PF was shown to have enhanced the vascularization of regenerated tissues and promote flap survival. However, the PF-mediated protection was partially lost after co-treatment with ML385, a selective Nrf2 inhibitor, suggesting that PF is a crucial modulator regulating the Nrf2/HO-1 signaling pathway. In summary, our data have provided a new insight into PF as a potential therapy for enhancing random-pattern flap viability.Jingtao JiangJingtao JiangJingtao JiangChengji DongChengji DongChengji DongLiang ZhaiJunsheng LouJunsheng LouJunsheng LouJie JinJie JinJie JinSheng ChengSheng ChengSheng ChengZhuliu ChenZhuliu ChenZhuliu ChenXiaoshan GuoXiaoshan GuoDamu LinDamu LinJian DingJian DingWeiyang GaoWeiyang GaoFrontiers Media S.A.articlepaeoniflorinrandom skin flapoxidative stressapoptosisangiogenesisNrf2/HO-1 signaling pathwayTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	paeoniflorin random skin flap oxidative stress apoptosis angiogenesis Nrf2/HO-1 signaling pathway Therapeutics. Pharmacology RM1-950
spellingShingle	paeoniflorin random skin flap oxidative stress apoptosis angiogenesis Nrf2/HO-1 signaling pathway Therapeutics. Pharmacology RM1-950 Jingtao Jiang Jingtao Jiang Jingtao Jiang Chengji Dong Chengji Dong Chengji Dong Liang Zhai Junsheng Lou Junsheng Lou Junsheng Lou Jie Jin Jie Jin Jie Jin Sheng Cheng Sheng Cheng Sheng Cheng Zhuliu Chen Zhuliu Chen Zhuliu Chen Xiaoshan Guo Xiaoshan Guo Damu Lin Damu Lin Jian Ding Jian Ding Weiyang Gao Weiyang Gao Paeoniflorin Suppresses TBHP-Induced Oxidative Stress and Apoptosis in Human Umbilical Vein Endothelial Cells via the Nrf2/HO-1 Signaling Pathway and Improves Skin Flap Survival
description	Random-pattern skin flap is a vital technique frequently applied in reconstruction surgeries for its convenience and effectiveness in solving skin defects. However, ischemic necrosis, especially in the distal areas of the flap, still needs extra attention after surgery. Earlier evidence has suggested that paeoniflorin (PF) could stimulate angiogenesis and suppress ischemic cardiovascular disease. However, few studies have focused on the role of PF in flap survival. In this study, we have demonstrated that the human umbilical vein endothelial cells (HUVECs) treated with PF can alleviate tert-butyl hydroperoxide (TBHP)-stimulated cellular dysfunction and apoptosis. To better evaluate, HUVECs’ physiology, cell tube formation, migration, and adhesion were assessed. Mechanistically, PF protects HUVECs against apoptosis via stimulating the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway. PF also downregulates mitochondrial ROS production to reduce excessive intracellular ROS production induced by TBHP and restore TBHP-induced mitochondrial depolarization. As a result, silencing Nrf2 partially abolishes the protective effect of PF exposure on HUVECs. In in vivo experiments, the oral administration of PF was shown to have enhanced the vascularization of regenerated tissues and promote flap survival. However, the PF-mediated protection was partially lost after co-treatment with ML385, a selective Nrf2 inhibitor, suggesting that PF is a crucial modulator regulating the Nrf2/HO-1 signaling pathway. In summary, our data have provided a new insight into PF as a potential therapy for enhancing random-pattern flap viability.
format	article
author	Jingtao Jiang Jingtao Jiang Jingtao Jiang Chengji Dong Chengji Dong Chengji Dong Liang Zhai Junsheng Lou Junsheng Lou Junsheng Lou Jie Jin Jie Jin Jie Jin Sheng Cheng Sheng Cheng Sheng Cheng Zhuliu Chen Zhuliu Chen Zhuliu Chen Xiaoshan Guo Xiaoshan Guo Damu Lin Damu Lin Jian Ding Jian Ding Weiyang Gao Weiyang Gao
author_facet	Jingtao Jiang Jingtao Jiang Jingtao Jiang Chengji Dong Chengji Dong Chengji Dong Liang Zhai Junsheng Lou Junsheng Lou Junsheng Lou Jie Jin Jie Jin Jie Jin Sheng Cheng Sheng Cheng Sheng Cheng Zhuliu Chen Zhuliu Chen Zhuliu Chen Xiaoshan Guo Xiaoshan Guo Damu Lin Damu Lin Jian Ding Jian Ding Weiyang Gao Weiyang Gao
author_sort	Jingtao Jiang
title	Paeoniflorin Suppresses TBHP-Induced Oxidative Stress and Apoptosis in Human Umbilical Vein Endothelial Cells via the Nrf2/HO-1 Signaling Pathway and Improves Skin Flap Survival
title_short	Paeoniflorin Suppresses TBHP-Induced Oxidative Stress and Apoptosis in Human Umbilical Vein Endothelial Cells via the Nrf2/HO-1 Signaling Pathway and Improves Skin Flap Survival
title_full	Paeoniflorin Suppresses TBHP-Induced Oxidative Stress and Apoptosis in Human Umbilical Vein Endothelial Cells via the Nrf2/HO-1 Signaling Pathway and Improves Skin Flap Survival
title_fullStr	Paeoniflorin Suppresses TBHP-Induced Oxidative Stress and Apoptosis in Human Umbilical Vein Endothelial Cells via the Nrf2/HO-1 Signaling Pathway and Improves Skin Flap Survival
title_full_unstemmed	Paeoniflorin Suppresses TBHP-Induced Oxidative Stress and Apoptosis in Human Umbilical Vein Endothelial Cells via the Nrf2/HO-1 Signaling Pathway and Improves Skin Flap Survival
title_sort	paeoniflorin suppresses tbhp-induced oxidative stress and apoptosis in human umbilical vein endothelial cells via the nrf2/ho-1 signaling pathway and improves skin flap survival
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/6fe4cfca01da4411b1d62807b690bc23
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Paeoniflorin Suppresses TBHP-Induced Oxidative Stress and Apoptosis in Human Umbilical Vein Endothelial Cells via the Nrf2/HO-1 Signaling Pathway and Improves Skin Flap Survival

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