Preventive effect of hyperforin on lipopolysaccharide-induced acute kidney injury and inflammation by repressing the NF-κB/miR-21 axis.

Abstract

Hyperforin (HYP) has been reported to alleviate the inflammatory response. The purpose of this study was to examine the pharmacological effects of HYP on lipopolysaccharide (LPS)-induced inflammation and acute kidney injury (AKI). In vitro and in vivo septic models were created using LPS-stimulated mice podocytes and LPS-injected mice. HYP (20 mg/kg/day) or antagomiR-21 (20 nM/0.1 ml; twice/week) was administered to mitigate LPS-induced AKI and podocyte apoptosis. HYP demonstrated potential as an NF-κB inhibitor, leading to enhanced survival rates in septic mice. Moreover, HYP directly hindered LPS-induced podocyte apoptosis and AKI. The underlying mechanism involves the modulation of LPS-induced transactivation of miR-21 by NF-κB. It was observed that excessive activation of the NF-κB/miR-21 signaling axis contributed to LPS-induced podocyte apoptosis and AKI. Additionally, the absence of miR-21 expression resulted in decreased LPS-induced podocyte apoptosis and amelioration of LPS-induced renal tubular injury. The renoprotective effects of HYP were observed in septic mice through the inhibition of NF-κB/p65-mediated transactivation of miR-21. These findings suggest that targeting the NF-κB-miR-21 axis could be a potential therapeutic strategy for HYP in the prevention of AKI.