Donkey milk-induced PPARα activation enhances lipid metabolism and ameliorates renal fibrosis in CKD rats

Chronic kidney disease (CKD) is characterized by renal injury often accompanied by inflammation, oxidative stress, and disordered lipid metabolism. Donkey milk contains nutritional components making it suitable for patients with CKD. However, the effectiveness of donkey milk in improving lipid metabolism and renal fibrosis in CKD rats, along with its underlying mechanism, remains unclear. Renal function and histomorphology were determined to evaluate the ameliorative effect of donkey milk on renal injury. Potential targets and pathways associated with donkey milk's effects were predicted by network pharmacology. The levels of blood lipid, PPARα and the expression of key lipid metabolism targets were detected. Donkey milk exerts beneficial effects against CKD effects via 38 key targets including ApoA1, ApoB and ApoE, which are closely involved in lipid metabolism and the PPAR signaling pathway. Donkey milk alleviated lipid metabolism disorders in CKD via the PPARα pathway by upregulating fatty acid oxidation and inhibiting fatty acid synthesis. Donkey milk alleviates renal function and structural damage in CKD through multiple components, targets and pathways. And it improves cyclic lipid metabolism and reduces renal lipid deposition, which was associated with the regulation of PPARα-mediated target genes involved in fatty acid oxidation and synthesis. • Donkey milk ameliorated renal function, structural damage and fibrosis in UUO-induced CKD rats. • Network pharmacology revealed 38 key targets and core pathways (e.g., PPAR) for donkey milks anti-CKD effects, mainly related to lipid metabolism and inflammation. • Donkey milk activated renal PPARα in CKD rats, regulating fatty acid oxidation/synthesis-related genes to reduce renal lipid deposition and alleviate fibrosis.