Emodin Alleviates Lipid Accumulation and Renal Tubular Injury in Rats With DN via Inhibiting HIF-1α Expression.

Background: Our previous study verified that lipid nephrotoxicity mediated by hypoxia-inducible factor-1 alpha (HIF-1α) activation aggravates diabetic tubular injury. This study investigated whether emodin, an inhibitor of HIF-1α, improves tubular injury by reducing lipid accumulation in diabetic tubules, and examined its underlying mechanism. Methods: Type 1 diabetic rats were administered 40 mg/kg emodin by gavage daily. For the in vitro study, HK-2 cells were pretreated with emodin for 6 h and then stimulated with HIF-1α activator cobalt chloride (CoCl2). Results: In vivo, emodin significantly downregulated HIF-1α protein expression in the kidneys of rats with diabetes. Emodin treatment substantially attenuated tubular pathological damage and reduced 24-h urinary total protein levels and the urinary albumin-to-creatinine ratio in rats with diabetes, accompanied by decreased expression of transforming growth factor-beta 1 (TGF-β1) and connective tissue growth factor (CTGF). Meanwhile, lipid accumulation and mitochondrial dysfunction in diabetic kidneys markedly improved after emodin treatment. Similarly, in vitro, emodin effectively reduced HIF-1α protein expression in CoCl2-treated HK-2 cells. Moreover, emodin ameliorated lipid accumulation, cellular injury, and mitochondrial homeostasis imbalance in these cells. Conclusion: These data demonstrate that emodin prevents lipid accumulation and cellular injury in diabetic tubular epithelial cells, possibly by inhibiting HIF-1α activation and exerting a protective effect on mitochondria.