Qi‐dan‐dihuang decoction ameliorates renal fibrosis in diabetic rats via p38MAPK/AKT/mTOR signaling pathway

Abstract

AbstractContextQi‐dan‐dihuang decoction (QDD) has been used to treat diabetic kidney disease (DKD), but the underlying mechanisms are poorly understood.ObjectiveThis study reveals the mechanism by which QDD ameliorates DKD.Materials and MethodsThe compounds in QDD were identified by high‐performance liquid chromatography and quadrupole‐time‐of‐flight tandem mass spectrometry (HPLC‐Q‐TOF‐MS). Key targets and signaling pathways were screened through bioinformatics. Nondiabetic Lepr db/m mice were used as control group, while Lepr db/db mice were divided into model group, dapagliflozin group, 1% QDD‐low (QDD‐L), and 2% QDD‐high (QDD‐H) group. After 12 weeks of administration, 24 h urinary protein, serum creatinine, and blood urea nitrogen levels were detected. Kidney tissues damage and fibrosis were evaluated by pathological staining. In addition, 30 mmol/L glucose‐treated HK‐2 and NRK‐52E cells to induce DKD model. Cell activity and migration capacity as well as protein expression levels were evaluated.ResultsA total of 46 key target genes were identified. Functional enrichment analyses showed that key target genes were significantly enriched in the phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT) and mitogen‐activated protein kinase (MAPK) signaling pathways. In addition, in vivo and in vitro experiments confirmed that QDD ameliorated renal fibrosis in diabetic mice by resolving inflammation and inhibiting the epithelial‐mesenchymal transition (EMT) via the p38MAPK and AKT‐mammalian target of rapamycin (mTOR) pathways.Discussion and ConclusionQDD inhibits EMT and the inflammatory response through the p38MAPK and AKT/mTOR signaling pathways, thereby playing a protective role in renal fibrosis in DKD.