Qidantang Granule Ameliorates Diabetic Kidney Disease in Mice by Inhibiting Cuproptosis

Diabetic kidney disease (DKD) is a significant contributor to chronic kidney disease and end-stage renal disease. Cuproptosis, a newly recognized type of copper-dependent cellular demise, has been associated with the pathophysiology of DKD. Qidantang Granule, a traditional Chinese medicinal formulation, has demonstrated the renoprotective benefits, although its function in controlling cuproptosis is ambiguous. A mouse model of DKD was generated using streptozotocin (STZ) in male C57BL/6J mice. Mice received oral administration of Qidantang Granule (200 mg/kg/day) or a vehicle for a duration of 9 weeks. Renal function, histopathology, apoptosis, oxidative stress, and metabolic alterations were evaluated using biochemical tests, ELISA, and histological staining. Western blotting and qRT-PCR identified proteins and genes associated with apoptosis and cuproptosis, whereas inductively coupled plasma mass spectrometry assessed renal copper levels. Qidantang Granule treatment significantly reduced blood glucose levels, improved renal function parameters, and alleviated histological damage in DKD mice. Treatment inhibited Bax and active caspase-3 expression, decreased malondialdehyde levels, restored MnSOD activity and ATP content, and normalized levels of pyruvate, α-ketoglutarate, and succinic acid levels. Qidantang Granule decreased renal copper levels, downregulated SLC31A1 and Hsp70 expression, and reinstated lipoylation of dihydrolipoamide S-acetyltransferase and dihydrolipoamide S-succinyltransferase, signifying the suppression of cuproptosis. Qidantang Granule ameliorates DKD in STZ-induced mice by diminishing oxidative stress, modulating energy metabolism, and inhibiting cuproptosis, underscoring its promise as a treatment approach for DKD.