4.7 Article

Neferine Attenuates Acute Kidney Injury by Inhibiting NF-κB Signaling and Upregulating Klotho Expression

Journal

FRONTIERS IN PHARMACOLOGY
Volume 10, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2019.01197

Keywords

acute kidney injury (AKI); neferine; NF-kappa B; Klotho; apoptosis; inflammation

Funding

  1. National Youth Science Foundation of China [81600536]
  2. Natural Science Foundation of Hunan Province of China [2018JJ3833, 2018JJ3818]

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Purpose: Morbidity associated with and mortality from acute kidney injury (AKI) is gradually increasing, and no efficient drug is available. We explored whether neferine, a bisbenzylisoquinoline alkaloid, attenuated AKI, and the possible mechanisms in play in vivo and in vitro. Methods: We induced AKI using ischemia-reperfusion (I/R) or lipopolysaccharide (LPS) in vivo. C57 BL/6 male mice were randomized into two groups each containing four subgroups: control, neferine, I/R or LPS, and I/R or LPS + neferine. Mice were sacrificed 24 h after AKI induction and kidneys and sera were collected. NRK-52E cells were exposed to hypoxia/reoxygenation (H/R) or LPS in vitro. Results: Neferine pretreatment significantly alleviated kidney functional loss and pathological damage. In the AKI mouse models induced by I/R or LPS, neferine inhibited the infiltration of inflammatory cells, including granulocytes and macrophages. Both in vivo and in vitro, neferine attenuated apoptosis, suppressed inflammatory cytokine production, decreased degradation of kappa B-alpha, and inhibited nuclear translocation of NF-kappa B. Furthermore, it also upregulated Klotho expression in AKI. Conclusion: Neferine mitigated renal injury in AKI models, perhaps by suppressing the activation of NF-kappa B and upregulating the expression of Klotho.

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