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Xuebijing Injection Maintains GRP78 Expression to Prevent Candida albicans–Induced Epithelial Death in the Kidney

Sepsis and septic shock threaten the survival of millions of patients in the intensive care unit. Secondary fungal infections significantly increased the risk of mortality in sepsis patients. Chinese medicine Xuebijing injection (XBJ) has been routinely used as an add-on treatment to sepsis and sept...

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Autores principales: Shang, Ting, Yu, Qilin, Ren, Tongtong, Wang, Xin-Tong, Zhu, Hongyan, Gao, Jia-Ming, Pan, Guixiang, Gao, Xiumei, Zhu, Yan, Feng, Yuxin, Li, Ming-Chun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956827/
https://www.ncbi.nlm.nih.gov/pubmed/31969817
http://dx.doi.org/10.3389/fphar.2019.01416
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author Shang, Ting
Yu, Qilin
Ren, Tongtong
Wang, Xin-Tong
Zhu, Hongyan
Gao, Jia-Ming
Pan, Guixiang
Gao, Xiumei
Zhu, Yan
Feng, Yuxin
Li, Ming-Chun
author_facet Shang, Ting
Yu, Qilin
Ren, Tongtong
Wang, Xin-Tong
Zhu, Hongyan
Gao, Jia-Ming
Pan, Guixiang
Gao, Xiumei
Zhu, Yan
Feng, Yuxin
Li, Ming-Chun
author_sort Shang, Ting
collection PubMed
description Sepsis and septic shock threaten the survival of millions of patients in the intensive care unit. Secondary fungal infections significantly increased the risk of mortality in sepsis patients. Chinese medicine Xuebijing injection (XBJ) has been routinely used as an add-on treatment to sepsis and septic shock in China. Our network pharmacology analysis predicted that XBJ also influences fungal infection, consisting with results of pioneer clinical studies. We conducted in vivo and in vitro experiments to verify this prediction. To our surprise, XBJ rescued mice from lethal Candida sepsis in a disseminated Candida albicans infection model and abolished the colonization of C. albicans in kidneys. Although XBJ did not inhibit the growth and the virulence of C. albicans in vitro, it enhanced the viability of 293T cells upon C. albicans insults. Further RNA-seq analysis revealed that XBJ activated the endoplasmic reticulum (ER) stress pathway upon C. albicans infection. Western blot confirmed that XBJ maintained the expression of GRP78 in the presence of C. albicans. Interestingly, key active ingredients in XBJ (C0127) mirrored the effects of XBJ. C0127 not only rescued mice from lethal Candida sepsis and prevented the colonization of C. albicans in kidneys, but also sustained the survival of kidney epithelial cells partially by maintaining the expression of GRP78. These results suggested that XBJ may prevent fungal infection in sepsis patients. Pre-activation of ER stress pathway is a novel strategy to control C. albicans infection. Network pharmacology may accelerate drug development in the field of infectious diseases.
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spelling pubmed-69568272020-01-22 Xuebijing Injection Maintains GRP78 Expression to Prevent Candida albicans–Induced Epithelial Death in the Kidney Shang, Ting Yu, Qilin Ren, Tongtong Wang, Xin-Tong Zhu, Hongyan Gao, Jia-Ming Pan, Guixiang Gao, Xiumei Zhu, Yan Feng, Yuxin Li, Ming-Chun Front Pharmacol Pharmacology Sepsis and septic shock threaten the survival of millions of patients in the intensive care unit. Secondary fungal infections significantly increased the risk of mortality in sepsis patients. Chinese medicine Xuebijing injection (XBJ) has been routinely used as an add-on treatment to sepsis and septic shock in China. Our network pharmacology analysis predicted that XBJ also influences fungal infection, consisting with results of pioneer clinical studies. We conducted in vivo and in vitro experiments to verify this prediction. To our surprise, XBJ rescued mice from lethal Candida sepsis in a disseminated Candida albicans infection model and abolished the colonization of C. albicans in kidneys. Although XBJ did not inhibit the growth and the virulence of C. albicans in vitro, it enhanced the viability of 293T cells upon C. albicans insults. Further RNA-seq analysis revealed that XBJ activated the endoplasmic reticulum (ER) stress pathway upon C. albicans infection. Western blot confirmed that XBJ maintained the expression of GRP78 in the presence of C. albicans. Interestingly, key active ingredients in XBJ (C0127) mirrored the effects of XBJ. C0127 not only rescued mice from lethal Candida sepsis and prevented the colonization of C. albicans in kidneys, but also sustained the survival of kidney epithelial cells partially by maintaining the expression of GRP78. These results suggested that XBJ may prevent fungal infection in sepsis patients. Pre-activation of ER stress pathway is a novel strategy to control C. albicans infection. Network pharmacology may accelerate drug development in the field of infectious diseases. Frontiers Media S.A. 2020-01-06 /pmc/articles/PMC6956827/ /pubmed/31969817 http://dx.doi.org/10.3389/fphar.2019.01416 Text en Copyright © 2020 Shang, Yu, Ren, Wang, Zhu, Gao, Pan, Gao, Zhu, Feng and Li http://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
Shang, Ting
Yu, Qilin
Ren, Tongtong
Wang, Xin-Tong
Zhu, Hongyan
Gao, Jia-Ming
Pan, Guixiang
Gao, Xiumei
Zhu, Yan
Feng, Yuxin
Li, Ming-Chun
Xuebijing Injection Maintains GRP78 Expression to Prevent Candida albicans–Induced Epithelial Death in the Kidney
title Xuebijing Injection Maintains GRP78 Expression to Prevent Candida albicans–Induced Epithelial Death in the Kidney
title_full Xuebijing Injection Maintains GRP78 Expression to Prevent Candida albicans–Induced Epithelial Death in the Kidney
title_fullStr Xuebijing Injection Maintains GRP78 Expression to Prevent Candida albicans–Induced Epithelial Death in the Kidney
title_full_unstemmed Xuebijing Injection Maintains GRP78 Expression to Prevent Candida albicans–Induced Epithelial Death in the Kidney
title_short Xuebijing Injection Maintains GRP78 Expression to Prevent Candida albicans–Induced Epithelial Death in the Kidney
title_sort xuebijing injection maintains grp78 expression to prevent candida albicans–induced epithelial death in the kidney
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956827/
https://www.ncbi.nlm.nih.gov/pubmed/31969817
http://dx.doi.org/10.3389/fphar.2019.01416
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