Phytomedicine : international journal of phytotherapy and phytopharmacologyJun 21, 2024

Puerarin reduces kidney inflammation by blocking immune cell activation through TLR4/MyD88-triggered pathways

Updated Mar 6, 2026

Abstract

Puerarin administration significantly alleviated kidney dysfunction and reduced inflammation in mouse models of acute kidney injury (AKI).

Puerarin effectively reduced inflammatory responses in both lipopolysaccharide (LPS)-induced and unilateral ureteral obstruction (UUO)-induced AKI models.
In vitro, puerarin inhibited the polarization of M1 macrophages and decreased the release of inflammatory factors in LPS-stimulated macrophages.
Puerarin downregulated the activity of the NF-κB p65 and JNK/FoxO1 signaling pathways.
Activation of FoxO1 or JNK reversed the inhibitory effects of puerarin on macrophage polarization and inflammatory factor release.
Puerarin binds to the Toll/interleukin-1 receptor (TIR) domain of MyD88, disrupting its interaction with TLR4 and leading to the inactivation of downstream signaling.

Simplified

BACKGROUND: Acute kidney injury (AKI) is a clinically common and serious renal dysfunction, characterized by inflammation and damage to tubular epithelial cells. Puerarin, an isoflavone derivative isolated from Pueraria lobata, has been proven to possess exceptional effectiveness in reducing inflammation. However, the effects and underlying mechanisms of puerarin on AKI remain uncertain.

PURPOSE: This study investigated the possible therapeutic effects of puerarin on AKI and explored its underlying mechanism.

STUDY DESIGN AND METHODS: The effects of puerarin on AKI and macrophage polarization were investigated in lipopolysaccharide (LPS)-induced or unilateral ureteral obstruction (UUO)-induced mouse models in vivo and LPS-treated macrophages (Raw264.7) in vitro. Additionally, the effects of puerarin on inflammation-related signaling pathways were analyzed.

RESULTS: Administration of puerarin effectively alleviated kidney dysfunction and reduced inflammatory response in LPS-induced and UUO-induced AKI. In vitro, puerarin treatment inhibited the polarization of M1 macrophages and the release of inflammatory factors in Raw264.7 cells stimulated by LPS. Mechanistically, puerarin downregulated the activities of NF-κB p65 and JNK/FoxO1 signaling pathways. The application of SRT1460 to activate FoxO1 or anisomycin to activate JNK eliminated puerarin-mediated inhibition of JNK/FoxO1 signaling, leading to suppression of macrophage M1 polarization and reduction of inflammatory factors. Further studies showed that puerarin bound to Toll/interleukin-1 receptor (TIR) domain of MyD88 protein, hindering its binding with TLR4, ultimately resulting in downstream NF-κB p65 and JNK/FoxO1 signaling inactivation.

CONCLUSIONS: Puerarin antagonizes NF-κB p65 and JNK/FoxO1 activation via TLR4/MyD88 pathway, thereby suppressing macrophage polarization towards M1 phenotype and alleviating renal inflammatory damage.

Full Text

Full text is available at the source.

View Full Text ↗

Abstract

Full Text

what lands in your inbox each week: