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Paeoniflorin Inhibits ASK1-TF Axis by Up-Regulating SOCS3 to Alleviate Radiation Enteritis

Radiation enteritis is one of the main adverse effects of radiotherapy, presenting with a poorly understood etiology and limited options for therapy. Intestinal inflammation and ischemia are the core mechanisms of radiation enteritis. Suppressor of cytokine signaling 3 (SOCS3) is an endogenous “infl...

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Autores principales: Sheng, Lei, Hu, Fan, Yu, Hanqing, Tao, Xueyou, Jia, Rumeng, Gu, Yufeng, Chen, Lu, Kong, Hong, Miao, Chen, Fei, Wenjing, Yang, Yang, Jia, Jinhui, Zhu, Xia, He, Xueming, Hu, Liang, Ma, Jianxin, Liu, Wen-Tao, Yang, Mi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8964139/
https://www.ncbi.nlm.nih.gov/pubmed/35359871
http://dx.doi.org/10.3389/fphar.2022.743708
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author Sheng, Lei
Hu, Fan
Yu, Hanqing
Tao, Xueyou
Jia, Rumeng
Gu, Yufeng
Chen, Lu
Kong, Hong
Miao, Chen
Fei, Wenjing
Yang, Yang
Jia, Jinhui
Zhu, Xia
He, Xueming
Hu, Liang
Ma, Jianxin
Liu, Wen-Tao
Yang, Mi
author_facet Sheng, Lei
Hu, Fan
Yu, Hanqing
Tao, Xueyou
Jia, Rumeng
Gu, Yufeng
Chen, Lu
Kong, Hong
Miao, Chen
Fei, Wenjing
Yang, Yang
Jia, Jinhui
Zhu, Xia
He, Xueming
Hu, Liang
Ma, Jianxin
Liu, Wen-Tao
Yang, Mi
author_sort Sheng, Lei
collection PubMed
description Radiation enteritis is one of the main adverse effects of radiotherapy, presenting with a poorly understood etiology and limited options for therapy. Intestinal inflammation and ischemia are the core mechanisms of radiation enteritis. Suppressor of cytokine signaling 3 (SOCS3) is an endogenous “inflammation brake.” We hypothesized that paeoniflorin, a pinane monoterpene bitter glycoside, could increase SOCS3 expression to reduce inflammation and ischemia and improve enteritis in mice. Laser Doppler flowmetry was used to detect changes in intestinal blood flow. RAW264.7 and human umbilical vein endothelial cells were used to investigate the mechanism of action of paeoniflorin. It was observed that radiation caused high mortality, intestinal inflammatory responses, and low blood flow in mice. Paeoniflorin effectively alleviated intestinal atrophy, prevented thrombosis, improved radiation enteritis, and reduced mortality in mice undergoing radiotherapy. In addition, paeoniflorin increased the release of growth arrest-specific gene 6 (Gas6) and phosphorylation of the Axl receptor, subsequently inducing the expression of SOCS3 and inhibiting the expression of p-apoptosis signal-regulating kinase 1 and tissue factor in vivo and in vitro. Based on our findings, we suggest that paeoniflorin is potentially effective in alleviating radiation enteritis via the activation of the Gas6/Axl/SOCS3 axis and subsequent reduction in intestinal inflammation and ischemia.
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spelling pubmed-89641392022-03-30 Paeoniflorin Inhibits ASK1-TF Axis by Up-Regulating SOCS3 to Alleviate Radiation Enteritis Sheng, Lei Hu, Fan Yu, Hanqing Tao, Xueyou Jia, Rumeng Gu, Yufeng Chen, Lu Kong, Hong Miao, Chen Fei, Wenjing Yang, Yang Jia, Jinhui Zhu, Xia He, Xueming Hu, Liang Ma, Jianxin Liu, Wen-Tao Yang, Mi Front Pharmacol Pharmacology Radiation enteritis is one of the main adverse effects of radiotherapy, presenting with a poorly understood etiology and limited options for therapy. Intestinal inflammation and ischemia are the core mechanisms of radiation enteritis. Suppressor of cytokine signaling 3 (SOCS3) is an endogenous “inflammation brake.” We hypothesized that paeoniflorin, a pinane monoterpene bitter glycoside, could increase SOCS3 expression to reduce inflammation and ischemia and improve enteritis in mice. Laser Doppler flowmetry was used to detect changes in intestinal blood flow. RAW264.7 and human umbilical vein endothelial cells were used to investigate the mechanism of action of paeoniflorin. It was observed that radiation caused high mortality, intestinal inflammatory responses, and low blood flow in mice. Paeoniflorin effectively alleviated intestinal atrophy, prevented thrombosis, improved radiation enteritis, and reduced mortality in mice undergoing radiotherapy. In addition, paeoniflorin increased the release of growth arrest-specific gene 6 (Gas6) and phosphorylation of the Axl receptor, subsequently inducing the expression of SOCS3 and inhibiting the expression of p-apoptosis signal-regulating kinase 1 and tissue factor in vivo and in vitro. Based on our findings, we suggest that paeoniflorin is potentially effective in alleviating radiation enteritis via the activation of the Gas6/Axl/SOCS3 axis and subsequent reduction in intestinal inflammation and ischemia. Frontiers Media S.A. 2022-03-14 /pmc/articles/PMC8964139/ /pubmed/35359871 http://dx.doi.org/10.3389/fphar.2022.743708 Text en Copyright © 2022 Sheng, Hu, Yu, Tao, Jia, Gu, Chen, Kong, Miao, Fei, Yang, Jia, Zhu, He, Hu, Ma, Liu and Yang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Sheng, Lei
Hu, Fan
Yu, Hanqing
Tao, Xueyou
Jia, Rumeng
Gu, Yufeng
Chen, Lu
Kong, Hong
Miao, Chen
Fei, Wenjing
Yang, Yang
Jia, Jinhui
Zhu, Xia
He, Xueming
Hu, Liang
Ma, Jianxin
Liu, Wen-Tao
Yang, Mi
Paeoniflorin Inhibits ASK1-TF Axis by Up-Regulating SOCS3 to Alleviate Radiation Enteritis
title Paeoniflorin Inhibits ASK1-TF Axis by Up-Regulating SOCS3 to Alleviate Radiation Enteritis
title_full Paeoniflorin Inhibits ASK1-TF Axis by Up-Regulating SOCS3 to Alleviate Radiation Enteritis
title_fullStr Paeoniflorin Inhibits ASK1-TF Axis by Up-Regulating SOCS3 to Alleviate Radiation Enteritis
title_full_unstemmed Paeoniflorin Inhibits ASK1-TF Axis by Up-Regulating SOCS3 to Alleviate Radiation Enteritis
title_short Paeoniflorin Inhibits ASK1-TF Axis by Up-Regulating SOCS3 to Alleviate Radiation Enteritis
title_sort paeoniflorin inhibits ask1-tf axis by up-regulating socs3 to alleviate radiation enteritis
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8964139/
https://www.ncbi.nlm.nih.gov/pubmed/35359871
http://dx.doi.org/10.3389/fphar.2022.743708
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