Yucan granules alleviate renal injury in diabetic nephropathy by targeting ECH1, DHRS4, ECI2, and ECHS1

Yucan granules (YCG) have demonstrated therapeutic benefits in reducing urinary total protein in patients with diabetic kidney disease (DKD); however, their renoprotective mechanisms remain unclear.

To evaluate the therapeutic efficacy of YCG in DKD and elucidate the underlying mechanisms using 4D label-free quantitative proteomics.

The principal components of YCG, together with serum and kidney metabolites after administration, were identified via UPLC-Q-TOF-MS. A DKD mouse model was established with streptozotocin with a high-fat, high-sugar diet. Mice were randomly assigned to six groups (n = 10 per group): negative control, DKD, low-dose YCG (1.5 g/kg), medium-dose YCG (3 g/kg), high-dose YCG (6 g/kg), and positive control (Losartan potassium at 10 mg/kg) groups. After an 8-week treatment period, renal function and injury were assessed by biochemical analysis, histopathology, and fibrosis staining. 4D proteomics and western blotting were performed to investigate mechanisms.

YCG significantly lowered blood glucose levels, 24-h proteinuria, urinary microalbumin levels, and the urinary albumin-to-creatinine ratio, while renal pathology improved markedly. YCG also suppressed the expression of fibrosis markers (Fn, Col-Ⅰ, TGF-β1, α-SMA, and N-cadherin) and podocyte-associated proteins (WT1 and Nephrin). Proteomics analysis highlighted ECH1, DHRS4, ECI2, and ECHS1 as potential targets. In total, 13 chemical constituents and 9 metabolites were detected in in serum and kidney samples.

YCG alleviates DKD-related renal injury, presumably by modulating ECH1, DHRS4, ECI2, and ECHS1 pathways.