Paeonol protects endotoxin-induced acute kidney injury: potential mechanism of inhibiting TLR4-NF-κB signal pathway
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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
Hua-Ying Fan, email: firstname.lastname@example.org
Dong Qi, email: email@example.com
Chen Yu, email: firstname.lastname@example.org
Keywords: paeonol, acute kidney injury, sepsis, TLR4, NF-κB signal pathway
Received: September 16, 2015 Accepted: January 23, 2016 Published: March 25, 2016
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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