Fructus arctii mitigates diabetic nephropathy via the Apoh/PPAR-γ pathway.

Mol Immunol

College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, Liaoning 116600, China. Electronic address:

Published: March 2025

Background: Diabetic nephropathy (DN) is characterized by renal fibrosis and functional decline. Apolipoprotein H (Apoh) and Fructus arctii, a traditional medicinal plant, have demonstrated potential in treating metabolic and fibrotic disorders. This study Focused on revealing the roles of Apoh and Fructus arctii in mitigating DN.

Methods: Db/db mice served as an in vivo DN model, and mouse glomerular mesangial cells (mMCs) and renal tubular epithelial cells (mTECs) were treated with high glucose (HG) to simulate DN in vitro. Apoh silencing and overexpression were performed using shRNA and pcDNA3.1 vectors. Fructus arctii was administered to both cellular and animal models to assess its therapeutic potential. Cellular proliferation was measured using CCK-8 and EdU assays, while fibrosis markers were analyzed by Western blot, IHC and RT-qPCR. PPAR-γ pathway involvement was confirmed through treatment with the antagonist GW9662. Renal structural changes were evaluated with histological staining including H&E, PAS, Masson's trichrome, and picrosirius red staining.

Results: Apoh expression was markedly reduced in HG-treated cells and the kidneys of db/db mice. Overexpression of Apoh suppressed HG-induced proliferation in mMCs and mTECs by downregulating cyclin D1 and PCNA. Additionally, Apoh overexpression alleviated fibrosis by reducing Fibronectin, Collagen I, and α-SMA levels, effects mediated through the PPAR-γ pathway. Treatment with the PPAR-γ antagonist GW9662 reversed these protective effects. In db/db mice, Fructus arctii administration improved renal function by reducing blood glucose, proteinuria, and renal collagen deposition. It also alleviated fibrosis and enhanced Apoh and PPAR-γ expression. Silencing Apoh nullified the protective effects of Fructus arctii on cell proliferation and fibrosis, confirming its reliance on the Apoh/PPAR-γ pathway.

Conclusion: Fructus arctii alleviated DN progression by modulating cell proliferation and renal fibrosis via the Apoh/PPAR-γ pathway.

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http://dx.doi.org/10.1016/j.molimm.2025.02.017DOI Listing

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