Schisandrin C attenuates renal damage in diabetic nephropathy by regulating macrophage polarization

This study aimed to investigate the protective effects of Schisandrin C during diabetic nephropathy (DN) treatment. After DN induction, mice were treated with Schisandrin C, and diabetic metabolic parameters and renal function-associated factors were measured. Renal structural damage was evaluated by hematoxylin and eosin (HE) and Masson's trichrome staining. Macrophage polarization and macrophage-mediated inflammatory factors were detected in the kidneys by immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA), respectively. The Swiprosin-1/interferon (IFN)-γ-Rβ pathway was evaluated by western blot (WB) analysis. The preliminary effects of Schisandrin C in high-glucose-stimulated macrophages from DN mice were verified by flow cytometry, ELISA, and WB analyses. These results indicated that Schisandrin C significantly regulated physiological parameters in DN. Renal structural damage was mitigated by Schisandrin C. In Schisandrin-C-treated groups, the expression levels of CD86, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β decreased, whereas CD206, IL-10, and transforming growth factor (TGF)-β expression levels increased. In vitro experiments indicated that among CD86⁺ cells, TNF-α, IL-6, and IL-1β expression levels significantly decreased, whereas among CD206⁺ cells, IL-10 and TGF-β expression increased following Schisandrin-C-treatment. Finally, Schisandrin C inhibited the expression of Swiprosin-1, IFN-γ-Rβ, phospho-Janus kinase 2 (p-JAK2), phospho-signal transducer and activator of transcription 1 (p-STAT1), and p-STAT3, in both DN model mice and high-glucose-stimulated RAW264.7 cells. The present study indicated a novel use for Schisandrin C to suppress DN progression, by promoting M1 to M2 macrophage polarization. Schisandrin C exerted protective effects against DN by regulating the polarization-dependent Swiprosin-1/IFN-γ-Rβ signaling pathway in macrophages.