Oncotarget

Research Papers:

Osthole protects sepsis-induced acute kidney injury via down-regulating NF-κB signal pathway

Chen Yu, Peng Li, Dong Qi, Lei Wang, Hong-lin Qu, Yue-juan Zhang, Xue-kai Wang and Hua-Ying Fan _

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Oncotarget. 2017; 8:4796-4813. https://doi.org/10.18632/oncotarget.13592

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Abstract

Chen Yu1,*, Peng Li2,*, Dong Qi2,*, Lei Wang3,*, Hong-lin Qu1, Yue-juan Zhang4, Xue-kai Wang5, Hua-Ying Fan5

1School of Pharmacy, Binzhou Medical University, 264003 Yantai, Shandong, P.R. China

2Department of Nephrology, Yu-Huang-Ding Hospital/Qingdao University, 264000 Yantai, Shandong, P.R. China

3Yantai Food and Drug Inspection Center, 264000 Yantai, Shandong, P.R. China

4Yantai Yan-Tai-Shan Hospital, Yantai, Shandong, P.R. China

5School 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

*These authors have contributed equally to this work

Correspondence to:

Chen Yu, email: yuchen810624@163.com

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

Keywords: osthole, sepsis, CLP, NF-κB signal pathway, acute kidney injury

Received: July 20, 2016    Accepted: November 08, 2016    Published: November 25, 2016

ABSTRACT

BACKGROUND AND PURPOSE: As a natural coumarin derivative from the Cnidium monnieri(L)Cusson fruit, osthole consists of 7-methoxy-8-isopentenoxy-coumarin. The purpose of this research is to study the mechanism and effect of osthole on sepsis-induced acute kidney injury.

EXPERIMENTAL APPROACH: The protective effect of osthole on mouse macrophage RAW 264.7 and HK-2 cells induced by LPS in vitro and on acute kidney injury model induced by sepsis and established by puncture and cecal ligation (CLP) in vivo were tested.

KEY RESULTS: Osthole (20, 40 mg·kg-1) group can greatly attenuate the changes of the score and kidney histopathology damage and enhance the survival time of septic mice. After the CLP surgery, degrees of SCr and BUN related to kidney injury were upregulated. The concentrations of SCr and BUN can be greatly reduced by treatment with osthole. Furthermore, osthole could increase bacterial killing activity and phagocytic activities of macrophages impaired after CLP partly and attenuate blood bacterial counts and leukocyte infiltration markedly. Furthermore, osthole can suppress NF-κB signal pathway through the inhibition of the nuclear translocation by regulating phosphorylation of IκBα and IKKβ and hinder the production of chemoattractant (MCP-1 and IL-8) and proinflammatory cytokines (TNF-α, IL-1β and IL-6).

CONCLUSION AND IMPLICATIONS: Mainly because of its immunomodulatory properties and anti-inflammatory activity, which might be closely associated with suppression of the stimulation of the NF-κB signal pathway, osthole has protective effect on sepsis-induced kidney injury. It can be seen from such evidence that osthole can be potentially applied in the treatment of acute kidney injury.


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