Penthorum chinense Pursh extract ameliorates lupus nephritis disease in MRL/lpr mice via the PPARγ/NFκB signaling axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Penthorum chinense Pursh (P. chinense), also known as Penthorum sedoides var chinense, is one of homology of medicine and food traditionally used by the Chinese Miao people and has shown beneficial potential effects in the clinical treatment of lupus nephritis (LN) and liver protection.

AIM OF THE STUDY: Pinocembrin and gallic acid derivatives-rich fraction from P. chinense (PGF) has shown antioxidant and anti-lipidemic activities, yet its therapeutic potential in LN via macrophage PPARγ pathway modulation remains unexplored. In this study, we treated MRL/lpr mice with PGF to assess its therapeutic effects and verified its regulating signaling pathway through cytological experiments.

MATERIALS AND

METHODS

Chemical profiling of PGF was performed using UPLC-Q-TOF/MS. LN progression and PGF efficacy were evaluated in MRL/lpr mice via renal function assays and histopathological analysis (immunofluorescence). Integrated transcriptomics, metabolomics, and single-cell RNA sequencing were employed to identify PGF-targeted pathways. PPARγ/NFκB signaling modulation by PGF was validated in LPS-induced Raw264.7 macrophages and HK2 cells using western blotting, dual-luciferase reporter assays, and RT-qPCR.

RESULTS

PGF administration significantly attenuated lupus-like symptoms (e.g., proteinuria and anti-dsDNA antibodies) and mitigated renal pathology in MRL/lpr mice. Multi-omics analyses revealed that PGF reshaped macrophage differentiation and activated renal PPARγ signaling. Mechanistically, PGF upregulated PPARγ expression while suppressing NFκB phosphorylation in LPS-stimulated Raw264.7 macrophages, HK2 cells, and kidney tissues.

CONCLUSION

PGF ameliorates LN by modulating the PPARγ/NFκB axis in renal macrophages, highlighting its potential as a novel therapeutic strategy for LN through macrophage polarization regulation.