Oncotarget

Research Papers:

Paeonol protects endotoxin-induced acute kidney injury: potential mechanism of inhibiting TLR4-NF-κB signal pathway

Hua-Ying Fan _, Dong Qi, Chen Yu, Feng Zhao, Tao Liu, Zuo-Kai Zhang, Ming-Yan Yang, Lei-Ming Zhang, Da-Quan Chen and Yuan Du

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Oncotarget. 2016; 7:39497-39510. https://doi.org/10.18632/oncotarget.8347

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Abstract

Hua-Ying Fan1,*, Dong Qi2,*, Chen Yu3,*, Feng Zhao1,*, Tao Liu4, Zuo-Kai Zhang1, Ming-Yan Yang1, Lei-Ming Zhang1, Da-Quan Chen1, Yuan Du1

1School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, P.R. China

2Department of Nephrology, Yu-Huang-Ding Hospital/Qingdao University, Yantai, P.R. China

3School of Pharmacy, Binzhou Medical University, Yantai, P.R. China

4Center for Reproductive Medicine, Tai’an Central Hospital, Tai’an, P.R. China

*These authors contributed equally to this work

Correspondence to:

Hua-Ying Fan, email: katiefhydong@sina.com

Dong Qi, email: qidong8028@sina.com

Chen Yu, email: yuchen810624@163.com

Keywords: paeonol, acute kidney injury, sepsis, TLR4, NF-κB signal pathway

Received: September 16, 2015     Accepted: January 23, 2016     Published: March 25, 2016

ABSTRACT

Study design and methods: In order to determine the therapeutic effect and mechanism of paeonol on acute kidney injury induced by endotoxin, an acute kidney injury model was established by intraperitoneal administration of lipopolysaccharide in mice in vivo and on LPS-induced dendritic cells in vitro. Renal tissues were used for histologic examination. Concentrations of blood urea nitrogen and serum creatinine were detected, inflammatory cytokines were determined by ELISA. The relative proteins’ expression of TLR4-NF-κB signal pathway was assessed by Western blot, the localization and expression of phospho-NF-κB p65 in kidney was monitored by immunohistochemistry.

Results: Treatment of paeonol successfully cuts histopathological scores and dilutes the concentrations of blood urea nitrogen and serum creatinine as index of renal injury severity. In addition, paeonol reduces pro-inflammatory cytokines and increases anti-inflammatory cytokines stimulated by LPS in a dose-dependent manner. Paeonol also inhibits the expression of phosphorylated NF-κB p65, IκBα and IKKβ, and restrains NF-κB p65 DNA-binding activity. Paeonol treatment also attenuates the effects of LPS on dendritic cells, with significant inhibition of pro-inflammatory cytokines release, then TLR4 expression and NF-κB signal pathway have been suppressed.

Conclusions: These results indicated that paeonol has protective effects on endotoxin-induced kidney injury. The mechanisms underlying such effects are associated with its successfully attenuate inflammatory and suppresses TLR4 and NF-κB signal pathway. Therefore, paeonol has great potential to be a novel and natural product agent for treating AKI or septic-AKI.


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