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

• DOI: 10.1002/tox.24179
• Publication Date: 2024-03-08T09:45:35Z
• Authors: Liuyan Kuang; Yanting You; Jieying Qi; Jieyu Chen; Xinghong Zhou; Shuai Ji; Jingru Cheng; Hiu Yee Kwan; Pingping Jiang; Xiaomin Sun; Mengting Su; Ming Wang; Wenxiao Chen; Ren Luo; Xiaoshan Zhao; Lin Zhou
• Keywords: Male; 0303 health sciences; TOR Serine-Threonine Kinases; Kidney; Fibrosis; p38 Mitogen-Activated Protein Kinases; Diabetes Mellitus, Experimental; Rats; Cell Line; Rats, Sprague-Dawley; Mice; 03 medical and health sciences; Animals; Humans; Diabetic Nephropathies; Proto-Oncogene Proteins c-akt; Drugs, Chinese Herbal; Signal Transduction

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