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

Neferine mitigated renal injury in AKI models, perhaps by suppressing the activation of NF-κB and upregulating the expression of Klotho.

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.

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.

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 IκB-α, and inhibited nuclear translocation of NF-κB. Furthermore, it also upregulated Klotho expression in AKI.