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

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.