[Qihuang Jianpi Zishen Granule ameliorates renal injury in patients with systemic lupus erythematosus by regulating immunometabolic reprogramming of macrophages].

Abstract

Objectives: To investigate the mechanism of Qihuang Jianpi Zishen Granule (QJZG) for regulating macrophage polarization in renal damage in patients with systemic lupus erythematosus (SLE).

Methods: Public databases were used to screen the targets of QJZG, SLE and renal damage. An active ingredient-target network and a protein-protein interaction network were constructed followed by molecular docking. Sixty-two SLE patients were randomized into QJZG treatment group and control group (n=31), with 30 healthy individuals as the normal control group. Macrophage polarization markers (iNOS and Arg-1) and AMPK/ULK1 pathway molecules were detected using Western blotting and RT-qPCR, and the changes in renal function, immune indicators, and TCM syndrome scores of the participants were evaluated.

Results: Three key active ingredients of QJZG (quercetin, kaempferol, and 7-O-methylisoflavanone) and 9 core targets were identified, and the target genes were enriched in the TNF, HIF-1, and mTOR pathways. Molecular docking showed strong binding of the active compounds of QJZG with HIF-1α and mTOR. In SLE patients, QJZG treatment significantly improved their renal function, regulated the immune function (increasing CD4⁺/CD8⁺ ratio and reducing CD8⁺ T cells), and reduced TCM syndrome scores. QJZG treatment also significantly downregulated iNOS, mTOR, and HIF-1α expressions and upregulated Arg-1, AMPK, and ULK1 expression in SLE patients.

Conclusions: QJZG alleviated renal damage in SLE patients through a mechanism involving multiple components and targets. The active ingredients of QJZG regulate macrophage polarization possibly by activating the AMPK/ULK1 pathway via binding to their targets including HIF-1α and mTOR.