Osthole protects sepsis-induced acute kidney injury via down-regulating NF-κB signal pathway
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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
Chen Yu, email: [email protected]
Hua-Ying Fan, email: [email protected]
Keywords: osthole, sepsis, CLP, NF-κB signal pathway, acute kidney injury
Received: July 20, 2016 Accepted: November 08, 2016 Published: November 25, 2016
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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